WorldWideScience

Sample records for h1n1v vaccine development

  1. VACCINE-CHALLENGED IMMUNE RESISTANCE TOWARD VIRUS A/CALIFORNIA/7/2009(H1N1)v IN IMMUNIZED PREGNANT WOMEN

    OpenAIRE

    A. Cherdantsev; M. Kostinov; А. Kuselman; Y. Dagil; A.A. Savis’ko

    2012-01-01

    Abstract. We studied immune resistance efficiency of vaccination against influenza A/California/7/2009(H1N1)v in women at second trimester of physiological pregnancy in a blind, placebocontrolled study. The first group included thirty pregnant women who were injected by univalent subunit “MonoGrippol plus” vaccine. The second group consisted of thirty-seven pregnant women immunized by trivalent “Grippol plus” vaccine. Thirty-one pregnant women (III group) received placebo treatment. Non-pregn...

  2. Duration of (18)F-FDG avidity in lymph nodes after pandemic H1N1v and seasonal influenza vaccination

    DEFF Research Database (Denmark)

    Thomassen, Anders; Lerberg Nielsen, Anne; Gerke, Oke

    2011-01-01

    PURPOSE: The aim of our study was to investigate the occurrence of fluorodeoxyglucose (FDG) avidity in draining axillary lymph nodes after vaccination against influenza (H1N1v pandemic and seasonal) and to determine the period of increased FDG uptake. METHODS: During December 2009, patients...... axillary. If more vaccinations had been given, only the latest vaccination was evaluated in each deltoid region. RESULTS: Of all patients who underwent PET/CT scans during December 2009, 26% had been vaccinated with at least one influenza vaccination in the deltoid region. A total of 92 'draining' and 60...... lymph nodes. CONCLUSION: Influenza vaccination may lead to FDG-avid draining lymph nodes beyond 1 month....

  3. Duration of {sup 18}F-FDG avidity in lymph nodes after pandemic H1N1v and seasonal influenza vaccination

    Energy Technology Data Exchange (ETDEWEB)

    Thomassen, Anders; Lerberg Nielsen, Anne; Gerke, Oke; Johansen, Allan; Petersen, Henrik [OUH, Odense University Hospital, Department of Nuclear Medicine, Odense C (Denmark)

    2011-05-15

    The aim of our study was to investigate the occurrence of fluorodeoxyglucose (FDG) avidity in draining axillary lymph nodes after vaccination against influenza (H1N1v pandemic and seasonal) and to determine the period of increased FDG uptake. During December 2009, patients referred for {sup 18}F-FDG positron emission tomography (PET)/CT scans (n = 293) filled in a questionnaire concerning vaccination type (seasonal and/or H1N1v), time and anatomical localization of vaccination. Only injections in deltoid regions were evaluated, thus ensuring that draining lymph nodes were axillary. If more vaccinations had been given, only the latest vaccination was evaluated in each deltoid region. Of all patients who underwent PET/CT scans during December 2009, 26% had been vaccinated with at least one influenza vaccination in the deltoid region. A total of 92 'draining' and 60 'reference' (i.e. contralateral, non-vaccinated) axillary lymph nodes were evaluated in 61 patients (19 of 61 patients were scanned twice). The maximal intensity in FDG uptake (SUV{sub max}) in draining lymph nodes was 5 g/ml body weight (BW), whereas the maximal intensity in reference lymph nodes was 1.9 g/ml BW. The SUV{sub max} was normalized approximately 40 days after vaccination. No significant enlargement of metabolically active draining lymph nodes could be demonstrated on CT scan. Chemotherapy or immunosuppressive drugs given within 2 weeks from vaccination did not affect SUV{sub max} in the axillary lymph nodes. Influenza vaccination may lead to FDG-avid draining lymph nodes beyond 1 month. (orig.)

  4. VACCINE-CHALLENGED IMMUNE RESISTANCE TOWARD VIRUS A/CALIFORNIA/7/2009(H1N1v IN IMMUNIZED PREGNANT WOMEN

    Directory of Open Access Journals (Sweden)

    A. Cherdantsev

    2012-01-01

    Full Text Available Abstract. We studied immune resistance efficiency of vaccination against influenza A/California/7/2009(H1N1v in women at second trimester of physiological pregnancy in a blind, placebocontrolled study. The first group included thirty pregnant women who were injected by univalent subunit “MonoGrippol plus” vaccine. The second group consisted of thirty-seven pregnant women immunized by trivalent “Grippol plus” vaccine. Thirty-one pregnant women (III group received placebo treatment. Non-pregnant women (IV group were injected with “MonoGrippol plus”. We did not find any differences in clinical features of vacccine-challenged time period in pregnant women from groups I-III. Notably, sufficient numbers of women were found to be seroprotected 1 month post-vaccination (I group, 80.0% ; II group, 75.7% ; IVgroup, 80.6% with high levels seroconversion (I group, 46.6%; II group, 51.4%; IV group, 53.3%. Within 9-10 months after vaccination, a decreased seroprotection was revealed in II group of pregnant women. More stable specific immunity levels were detected for the groups immunized with univalent vaccine.Hence, the local subunit adjuvant “MonoGrippol plus” and “Grippol plus” vaccines were shown to exibit a high immune resistance efficiency profile and clinical safety, when used in pregnant women, thus presuming an extended application field for these biological drugs in public health service. State of pregnancy seems not to be a limiting condition for induction of specific immune resistance.

  5. French experience of 2009 A/H1N1v influenza in pregnant women.

    Science.gov (United States)

    Dubar, Grégory; Azria, Elie; Tesnière, Antoine; Dupont, Hervé; Le Ray, Camille; Baugnon, Thomas; Matheron, Sophie; Luton, Dominique; Richard, Jean-Christophe; Launay, Odile; Tsatsaris, Vassilis; Goffinet, François; Mignon, Alexandre

    2010-10-05

    The first reports on the pandemic influenza 2009 A/H1N1v from the USA, Mexico, and Australia indicated that this disease was associated with a high mortality in pregnant women. The aim of this study was to describe and compare the characteristics of severe critically ill and non-severe pregnant women with 2009 A/H1N1v-related illness in France. A national registry was created to screen pregnant women with laboratory-confirmed 2009 A/H1N1v influenza. Three hundred and fifteen patients from 46 French hospitals were included: 40 patients were admitted to intensive care units (severe outcomes), 111 were hospitalized in obstetric or medical wards (moderate outcomes), and 164 were outpatients (mild outcomes). The 2009 A/H1N1v influenza illness occurred during all pregnancy trimesters, but most women (54%), notably the severe patients (70%), were in the third trimester. Among the severe patients, twenty (50%) underwent mechanical ventilation, and eleven (28%) were treated with extracorporeal membrane oxygenation. Three women died from A/H1N1v influenza. We found a strong association between the development of a severe outcome and both co-existing illnesses (adjusted odds ratio [OR], 5.1; 95% confidence interval [CI], 2.2-11.8) and a delay in oseltamivir treatment after the onset of symptoms (>3 or 5 days) (adjusted OR, 4.8; 95% CI, 1.9-12.1 and 61.2, 95% CI; 14.4-261.3, respectively). Among the 140 deliveries after 22 weeks of gestation known to date, 19 neonates (14%) were admitted to a neonatal intensive care unit, mainly for preterm delivery, and two neonates died. None of these neonates developed 2009 A/H1N1v infection. This series confirms the high incidence of complications in pregnant women infected with pandemic A/H1N1v observed in other countries but depicts a lower overall maternal and neonatal mortality and morbidity than indicated in the USA or Australia. Moreover, our data demonstrate the benefit of early oseltamivir treatment in this specific population.

  6. French experience of 2009 A/H1N1v influenza in pregnant women.

    Directory of Open Access Journals (Sweden)

    Grégory Dubar

    Full Text Available BACKGROUND: The first reports on the pandemic influenza 2009 A/H1N1v from the USA, Mexico, and Australia indicated that this disease was associated with a high mortality in pregnant women. The aim of this study was to describe and compare the characteristics of severe critically ill and non-severe pregnant women with 2009 A/H1N1v-related illness in France. METHODOLOGY/PRINCIPAL FINDINGS: A national registry was created to screen pregnant women with laboratory-confirmed 2009 A/H1N1v influenza. Three hundred and fifteen patients from 46 French hospitals were included: 40 patients were admitted to intensive care units (severe outcomes, 111 were hospitalized in obstetric or medical wards (moderate outcomes, and 164 were outpatients (mild outcomes. The 2009 A/H1N1v influenza illness occurred during all pregnancy trimesters, but most women (54%, notably the severe patients (70%, were in the third trimester. Among the severe patients, twenty (50% underwent mechanical ventilation, and eleven (28% were treated with extracorporeal membrane oxygenation. Three women died from A/H1N1v influenza. We found a strong association between the development of a severe outcome and both co-existing illnesses (adjusted odds ratio [OR], 5.1; 95% confidence interval [CI], 2.2-11.8 and a delay in oseltamivir treatment after the onset of symptoms (>3 or 5 days (adjusted OR, 4.8; 95% CI, 1.9-12.1 and 61.2, 95% CI; 14.4-261.3, respectively. Among the 140 deliveries after 22 weeks of gestation known to date, 19 neonates (14% were admitted to a neonatal intensive care unit, mainly for preterm delivery, and two neonates died. None of these neonates developed 2009 A/H1N1v infection. CONCLUSIONS: This series confirms the high incidence of complications in pregnant women infected with pandemic A/H1N1v observed in other countries but depicts a lower overall maternal and neonatal mortality and morbidity than indicated in the USA or Australia. Moreover, our data demonstrate the

  7. Inside the outbreak of the 2009 influenza A (H1N1v virus in Mexico.

    Directory of Open Access Journals (Sweden)

    Hector M Zepeda-Lopez

    Full Text Available BACKGROUND: Influenza viruses pose a threat to human health because of their potential to cause global disease. Between mid March and mid April a pandemic influenza A virus emerged in Mexico. This report details 202 cases of infection of humans with the 2009 influenza A virus (H1N1v which occurred in Mexico City as well as the spread of the virus throughout the entire country. METHODOLOGY AND FINDINGS: From May 1st to May 5th nasopharyngeal swabs, derived from 751 patients, were collected at 220 outpatient clinics and 28 hospitals distributed throughout Mexico City. Analysis of samples using real time RT-PCR revealed that 202 patients out of the 751 subjects (26.9% were confirmed to be infected with the new virus. All confirmed cases of human infection with the strain influenza (H1N1v suffered respiratory symptoms. The greatest number of confirmed cases during the outbreak of the 2009 influenza A (H1N1v were seen in neighbourhoods on the northeast side of Mexico City including Iztapalapa, Gustavo A. Madero, Iztacalco, and Tlahuac which are the most populated areas in Mexico City. Using these data, together with data reported by the Mexican Secretariat of Health (MSH to date, we plot the course of influenza (H1N1v activity throughout Mexico. CONCLUSIONS: Our data, which is backed up by MSH data, show that the greatest numbers of the 2009 influenza A (H1N1 cases were seen in the most populated areas. We speculate on conditions in Mexico which may have sparked this flu pandemic, the first in 41 years. We accept the hypothesis that high population density and a mass gathering which took in Iztapalapa contributed to the rapid spread of the disease which developed in three peaks of activity throughout the Country.

  8. Inside the Outbreak of the 2009 Influenza A (H1N1)v Virus in Mexico

    Science.gov (United States)

    Zepeda-Lopez, Hector M.; Perea-Araujo, Lizbeth; Miliar-García, Angel; Dominguez-López, Aarón; Xoconostle-Cázarez, Beatriz; Lara-Padilla, Eleazar; Ramírez Hernandez, Jorge A.; Sevilla-Reyes, Edgar; Orozco, Maria Esther; Ahued-Ortega, Armando; Villaseñor-Ruiz, Ignacio; Garcia-Cavazos, Ricardo J.; Teran, Luis M.

    2010-01-01

    Background Influenza viruses pose a threat to human health because of their potential to cause global disease. Between mid March and mid April a pandemic influenza A virus emerged in Mexico. This report details 202 cases of infection of humans with the 2009 influenza A virus (H1N1)v which occurred in Mexico City as well as the spread of the virus throughout the entire country. Methodology and Findings From May 1st to May 5th nasopharyngeal swabs, derived from 751 patients, were collected at 220 outpatient clinics and 28 hospitals distributed throughout Mexico City. Analysis of samples using real time RT-PCR revealed that 202 patients out of the 751 subjects (26.9%) were confirmed to be infected with the new virus. All confirmed cases of human infection with the strain influenza (H1N1)v suffered respiratory symptoms. The greatest number of confirmed cases during the outbreak of the 2009 influenza A (H1N1)v were seen in neighbourhoods on the northeast side of Mexico City including Iztapalapa, Gustavo A. Madero, Iztacalco, and Tlahuac which are the most populated areas in Mexico City. Using these data, together with data reported by the Mexican Secretariat of Health (MSH) to date, we plot the course of influenza (H1N1)v activity throughout Mexico. Conclusions Our data, which is backed up by MSH data, show that the greatest numbers of the 2009 influenza A (H1N1) cases were seen in the most populated areas. We speculate on conditions in Mexico which may have sparked this flu pandemic, the first in 41 years. We accept the hypothesis that high population density and a mass gathering which took in Iztapalapa contributed to the rapid spread of the disease which developed in three peaks of activity throughout the Country. PMID:20949040

  9. Seroprevalence study in Vojvodina (Serbia following 2009 pandemic influenza A(H1N1v

    Directory of Open Access Journals (Sweden)

    Petrović Vladimir

    2012-01-01

    Full Text Available Introduction. The seroprevalence study was performed in Vojvodina during May and June 2010 in order to asses the effects of the 2009 pandemic influenza A(H1N1v epidemic on herd immunity. It was a part of the Serbian Ministry of Health funded nationwide study. Objective. Prevalence of antibodies against 2009 pandemic influenza A(H1N1v was determined in a 1% sample of the population monitored for influenza-like illness and acute respiratory infections in Vojvodina through sentinel surveillance system. Methods. The study sample involved a total of 1004 inhabitants of Vojvodina. The control group consisted of randomly selected and age-adjusted 1054 sera collected in the pre-pandemic period. Sera were tested by the reaction of hemagglutination inhibition using influenza A/California/7/2009 (H1N1 antigen in dilution from 1:8 to 1:256. Antibody titers ≥1:32 and ≥1:8 were considered protective and diagnostic, respectively. Results. The differences between control and study sera in all age groups were significant for both diagnostic ≥1/8 and protective titres ≥1/32 of hemagglutination inhibition antibodies (chi square test, p<0.001. The highest percentage of seropositive subjects was registered in the age group 15-19 years followed by children aged 5-14 years. Both diagnostic and protective titres were about twice higher in the vaccinated as compared to the non-vaccinated group. There were no statistically significant differences in seroprevalence between seven districts of Vojvodina. Conclusion. The 2009 pandemic influenza A(H1N1v epidemic significantly influenced the herd immunity in our population regardless of low immunization coverage with highest immunity levels in adolescents aged 15-19 years and with similar herd immunity levels in all the regions in the province six months after the outbreak.

  10. [Influenza A H1N1v treated with extra-corporal membrane oxygenation.

    DEFF Research Database (Denmark)

    Jensen, Reinhold; Severinsen, Inge Krogh; Terp, Kim

    2010-01-01

    . Polymerase chain reaction test for H1N1v was positive until day ten. No mutations were found in the virus. The patient was given oseltamivir tablets and inhalable zanamivir as well as antibiotics. The patient was treated with extra-corporal membrane oxygenation (EcmO) for 12 days followed by ventilator...

  11. Inside the Outbreak of the 2009 Influenza A (H1N1)v Virus in Mexico

    OpenAIRE

    Zepeda-Lopez, Hector M.; Lizbeth Perea-Araujo; Angel Miliar-García; Aarón Dominguez-López; Beatriz Xoconostle-Cázarez; Eleazar Lara-Padilla; Jorge A Ramírez Hernandez; Edgar Sevilla-Reyes; Maria Esther Orozco; Armando Ahued-Ortega; Ignacio Villaseñor-Ruiz; Garcia-Cavazos, Ricardo J.; Luis M Teran

    2010-01-01

    BACKGROUND: Influenza viruses pose a threat to human health because of their potential to cause global disease. Between mid March and mid April a pandemic influenza A virus emerged in Mexico. This report details 202 cases of infection of humans with the 2009 influenza A virus (H1N1)v which occurred in Mexico City as well as the spread of the virus throughout the entire country. METHODOLOGY AND FINDINGS: From May 1st to May 5th nasopharyngeal swabs, derived from 751 patients, were collected at...

  12. Acute Acalculous Cholecystitis due to Salmonella Enteritidis in a Child with Influenza A (H1N1)v

    OpenAIRE

    Regala, J.; Gouveia, C.; Brito, MJ

    2014-01-01

    A colecistite aguda acalculosa é uma entidade pouco frequente na idade pediátrica e uma complicação rara da enterocolite por salmonelas não tifóides. A co-infecçãocom o virus influenza A (H1N1)v nunca foi previamente descrita. Caso Clinico: Rapaz de 10 anos de idade, previamente saudável, com febre elevada, cefaleias , mialgias, vómitos e diarreia. a RT-PCR para virus influenza A, subtipo H1N1v foi postiva no exsudado nasofaríngeo mas não foi prescrito oseltamivir. Ao quinto dia da doença por...

  13. Epidemiological and transmissibility analysis of influenza A(H1N1)v in a southern hemisphere setting: Peru.

    Science.gov (United States)

    Munayco, C V; Gomez, J; Laguna-Torres, V A; Arrasco, J; Kochel, T J; Fiestas, V; Garcia, J; Perez, J; Torres, I; Condori, F; Nishiura, H; Chowell, G

    2009-08-13

    We present a preliminary analysis of 1,771 confirmed cases of influenza A(H1N1)v reported in Peru by 17 July including the frequency of the clinical characteristics, the spatial and age distribution of the cases and the estimate of the transmission potential. Age-specific frequency of cases was highest among school age children and young adults, with the lowest frequency of cases among seniors, a pattern that is consistent with reports from other countries. Estimates of the reproduction number lie in the range of 1.2 to 1.7, which is broadly consistent with previous estimates for this pandemic in other regions. Validation of these estimates will be possible as additional data become available.

  14. High burden of non-influenza viruses in influenza-like illness in the early weeks of H1N1v epidemic in France.

    Directory of Open Access Journals (Sweden)

    Nathalie Schnepf

    Full Text Available BACKGROUND: Influenza-like illness (ILI may be caused by a variety of pathogens. Clinical observations are of little help to recognise myxovirus infection and implement appropriate prevention measures. The limited use of molecular tools underestimates the role of other common pathogens. OBJECTIVES: During the early weeks of the 2009-2010 flu pandemic, a clinical and virological survey was conducted in adult and paediatric patients with ILI referred to two French University hospitals in Paris and Tours. Aims were to investigate the different pathogens involved in ILI and describe the associated symptoms. METHODS: H1N1v pandemic influenza diagnosis was performed with real time RT-PCR assay. Other viral aetiologies were investigated by the molecular multiplex assay RespiFinder19®. Clinical data were collected prospectively by physicians using a standard questionnaire. RESULTS: From week 35 to 44, endonasal swabs were collected in 413 patients. Overall, 68 samples (16.5% were positive for H1N1v. In 13 of them, other respiratory pathogens were also detected. Among H1N1v negative samples, 213 (61.9% were positive for various respiratory agents, 190 in single infections and 23 in mixed infections. The most prevalent viruses in H1N1v negative single infections were rhinovirus (62.6%, followed by parainfluenza viruses (24.2% and adenovirus (5.3%. 70.6% of H1N1v cases were identified in patients under 40 years and none after 65 years. There was no difference between clinical symptoms observed in patients infected with H1N1v or with other pathogens. CONCLUSION: Our results highlight the high frequency of non-influenza viruses involved in ILI during the pre-epidemic period of a flu alert and the lack of specific clinical signs associated with influenza infections. Rapid diagnostic screening of a large panel of respiratory pathogens may be critical to define and survey the epidemic situation and to provide critical information for patient management.

  15. Robust reconstruction and analysis of outbreak data: influenza A(H1N1)v transmission in a school-based population.

    Science.gov (United States)

    Hens, Niel; Calatayud, Laurence; Kurkela, Satu; Tamme, Teele; Wallinga, Jacco

    2012-08-01

    The rapid spread of the new influenza virus A(H1N1)v in young age groups in 2009 has been partly attributed to a high transmission intensity in schools. However, detailed characterization of the spread of influenza in school populations has been difficult to obtain, simply because it is very hard to identify who infected whom in a large outbreak. Data collected in large outbreak investigations typically miss many transmission events, and some reported transmission events will be incorrect. Here the authors present robust likelihood-based methods that can be used to analyze outbreak data while explicitly accounting for both missing data and erroneous data. They apply this method to a school-based outbreak of pandemic influenza A(H1N1)v that occurred in London, United Kingdom, in April 2009. The authors show that the generation interval in this school-based population was 2.20 days and that the reproduction number declined coincident with school closure, from 1.33 secondary cases per primary case to 0.43 secondary cases per primary case. These results provide quantitative evidence for the change in influenza transmission that is to be expected from school closure.

  16. Alteraciones morfológicas en pulmón por la influenza A H1N1/v09 en autopsias, Colombia, 2009

    Directory of Open Access Journals (Sweden)

    Jorge Rivera

    2011-03-01

    Conclusión. El porcentaje bajo de infección bacteriana concomitante observado en los casos de influenza A H1N1/ v09 en este estudio, es una característica sobresaliente que sugiere que el resultado fatal de la infección, probablemente no esté asociado a una enfermedad bacteriana secundaria, como se ha sugerido en reportes previos. Es probable que las lesiones observadas se puedan atribuir al daño tisular en la respuesta inflamatoria celular y humoral asociada a la infiltración por células poliformonucleares y macrófagos en el intersticio y la luz alveolares, como también por la lesión viral.

  17. The impact of communications about swine flu (influenza A H1N1v) on public responses to the outbreak: results from 36 national telephone surveys in the UK.

    Science.gov (United States)

    Rubin, G J; Potts, H W W; Michie, S

    2010-07-01

    To assess the association between levels of worry about the possibility of catching swine flu and the volume of media reporting about it; the role of psychological factors in predicting likely uptake of the swine flu vaccine; and the role of media coverage and advertising in predicting other swine flu-related behaviours. Data from a series of random-digit-dial telephone surveys were analysed. A time series analysis tested the association between levels of worry and the volume of media reporting on the start day of each survey. Cross-sectional regression analyses assessed the relationships between likely vaccine uptake or behaviour and predictor variables. Thirty-six surveys were run at, on average, weekly intervals across the UK between 1 May 2009 and 10 January 2010. Five surveys (run between 14 August and 13 September) were used to assess likely vaccine uptake. Five surveys (1-17 May) provided data relating to other behaviours. Between 1047 and 1173 people aged 16 years or over took part in each survey: 5175 participants provided data about their likely uptake of the swine flu vaccine; 5419 participants provided data relating to other behaviours. All participants were asked to state how worried they were about the possibility of personally catching swine flu. Subsets were asked how likely they were to take up a swine flu vaccination if offered it and whether they had recently carried tissues with them, bought sanitising hand gel, avoided using public transport or had been to see a general practitioner, visited a hospital or called NHS Direct for a flu-related reason. The percentage of 'very' or 'fairly' worried participants fluctuated between 9.6% and 32.9%. This figure was associated with the volume of media reporting, even after adjusting for the changing severity of the outbreak [chi2(1) = 6.6, p = 0.010, coefficient for log-transformed data = 2.6]. However, this effect only occurred during the UK's first summer wave of swine flu. In total, 56.1% of

  18. [Developments in HPV vaccination].

    Science.gov (United States)

    de Melker, Hester; Kenter, Gemma; van Rossum, Tekla; Conyn-van Spaendonck, Marina

    2012-01-01

    Vaccination against the human papilloma virus (HPV) has been included in the national Vaccination Programme of the Netherlands for 12-year-old girls since 2010. Vaccination coverage for the birth cohort of 1997 was 56.; there is a gradual increase in uptake. Continuous safety monitoring brought no new unknown serious side effects to light; many girls suffered from transient symptoms such as painful arm, fatigue and headache. After the current vaccines that protect against HPV types 2 and 4 types, respectively and induce some cross protection, vaccines are being developed that can induce broader protection. HPV vaccination of 12-year-old girls is cost-effective, even for relatively low vaccination coverage. The potential protection of HPV vaccination extends beyond prevention of cervical cancer by preventing other oncological manifestations of HPV infection in women as well as men and genital warts. The preventive HPV vaccines do not appear to be effective in treating existing abnormalities.

  19. Поствакцинальный иммунитет к вирусу гриппа A/California/7/2009(H1N1)v у иммунизированных беременных

    OpenAIRE

    Костинов, М.; Кусельман, А.; Дагиль, Ю.; Сависько, А.; Черданцев, Александр

    2012-01-01

    В слепом, плацебо-контролируемом исследовании изучали иммунологическую эффективность вакцинации против гриппа A/California/7/2009(H1N1)v у женщин на 2-м триместре физиологической беременности. I гр. 30 беременных, которым вводилась моновалентная субъединичная вакцина «МоноГриппол плюс», II гр. 37 беременных, получившие трехвалентную вакцину «Гриппол плюс», III гр. 31 беременная, которым вводился плацебо-препарат, IV гр. небеременные женщины, получившие «МоноГриппол плюс» В динамике наблюдения...

  20. Vaccine development for syphilis.

    Science.gov (United States)

    Lithgow, Karen V; Cameron, Caroline E

    2017-01-01

    Syphilis, caused by the spirochete Treponema pallidum subspecies pallidum, continues to be a globally prevalent disease despite remaining susceptible to penicillin treatment. Syphilis vaccine development is a viable preventative approach that will serve to complement public health-oriented syphilis prevention, screening and treatment initiatives to deliver a two-pronged approach to stemming disease spread worldwide. Areas covered: This article provides an overview of the need for development of a syphilis vaccine, summarizes significant information that has been garnered from prior syphilis vaccine studies, discusses the critical aspects of infection that would have to be targeted by a syphilis vaccine, and presents the current understanding within the field of the correlates of protection needed to be achieved through vaccination. Expert commentary: Syphilis vaccine development should be considered a priority by industry, regulatory and funding agencies, and should be appropriately promoted and supported.

  1. Efficacy of a pandemic (H1N1) 2009 virus vaccine in pigs against the pandemic influenza virus is superior to commercially available swine influenza vaccines.

    NARCIS (Netherlands)

    Loeffen, W.L.A.; Stockhofe-Zurwieden, N.; Weesendorp, E.; Zoelen-Bos, van D.J.; Heutink, R.; Quak, J.; Goovaerts, D.; Heldens, J.; Maas, H.A.; Moormann, R.J.M.; Koch, G.

    2011-01-01

    In April 2009 a new influenza A/H1N1 strain, currently named “pandemic (H1N1) influenza 2009¿ (H1N1v), started the first official pandemic in humans since 1968. Several incursions of this virus in pig herds have also been reported from all over the world. Vaccination of pigs may be an option to

  2. Pandemic influenza A(H1N1) 2009 vaccines in the European Union.

    Science.gov (United States)

    Johansen, K; Nicoll, A; Ciancio, B C; Kramarz, P

    2009-10-15

    Pandemic vaccines from four manufacturers are now available for use within the European Union (EU). Use of these vaccines will protect individuals and reduce the impact on health services to more manageable levels. The majority of the severely ill will be from known risk groups and the best strategy will be to start vaccinating in line with the recommendation from the European Union Health Security Committee prioritizing adults and children with chronic conditions, pregnant women and healthcare workers. The composition of authorized vaccines is reviewed in this article. The vaccine strain in all authorized pandemic vaccines worldwide is based on the same initial isolate of influenza A/California/7/2009 (H1N1)v but the vaccines differ in conditions for virus propagation, antigen preparation, antigen content and whether they are adjuvanted or not. The vaccines are likely to be effective since no significant genetic or antigenic drift has occurred and there are already mechanisms for estimating clinical effectiveness. Influenza vaccines have good safety records and no safety concerns have so far been encountered with any of the vaccines developed. However, special mechanisms have been devised for the early detection and rigorous investigation of possible significant side effects in Europe through post-marketing surveillance and analysis. Delivery of the vaccines to the risk groups will pose difficulties where those with chronic illnesses are not readily identifiable to the healthcare services. There is considerable scope for European added value through Member States with excess vaccines making them available to other states.

  3. [Development of oral vaccines].

    Science.gov (United States)

    Matsubara, Akihiro; Shimizu, Yuya; Karamatsu, Katsuo; Yasutomi, Yasuhiro

    2008-10-01

    In the increasing crisis of pandemic of infectious diseases all over the world in recent years, it is the most necessary to develop readily available vaccines even in developing countries. Since many pathogens establish their initial infections through the mucosal surface in our bodies, the induction of mucosal immune responses by vaccines are thought to be important for the prevention of infectious diseases through mucosal site. Oral administration of vaccines has abilities to elicit mucosal immune responses at mucosal tissues with various advantages such as easy skill for administration, less stressful for vaccine recipients and safer than systemic injection. Here, we show our novel strategies for inducing mucosal immune responses by oral vaccine administration.

  4. [Development of new vaccines].

    Science.gov (United States)

    González-Romo, Fernando; Picazo, Juan J

    2015-10-01

    Recent and important advances in the fields of immunology, genomics, functional genomics, immunogenetics, immunogenomics, bioinformatics, microbiology, genetic engineering, systems biology, synthetic biochemistry, proteomics, metabolomics and nanotechnology, among others, have led to new approaches in the development of vaccines. The better identification of ideal epitopes, the strengthening of the immune response due to new adjuvants, and the search of new routes of vaccine administration, are good examples of advances that are already a reality and that will favour the development of more vaccines, their use in indicated population groups, or its production at a lower cost. There are currently more than 130 vaccines are under development against the more wished (malaria or HIV), difficult to get (CMV or RSV), severe re-emerging (Dengue or Ebola), increasing importance (Chagas disease or Leishmania), and nosocomial emerging (Clostridium difficile or Staphylococcus aureus) infectious diseases. Copyright © 2015. Published by Elsevier España, S.L.U.

  5. Efficacy of a pandemic (H1N1) 2009 virus vaccine in pigs against the pandemic influenza virus is superior to commercially available swine influenza vaccines.

    Science.gov (United States)

    Loeffen, W L A; Stockhofe, N; Weesendorp, E; van Zoelen-Bos, D; Heutink, R; Quak, S; Goovaerts, D; Heldens, J G M; Maas, R; Moormann, R J; Koch, G

    2011-09-28

    In April 2009 a new influenza A/H1N1 strain, currently named "pandemic (H1N1) influenza 2009" (H1N1v), started the first official pandemic in humans since 1968. Several incursions of this virus in pig herds have also been reported from all over the world. Vaccination of pigs may be an option to reduce exposure of human contacts with infected pigs, thereby preventing cross-species transfer, but also to protect pigs themselves, should this virus cause damage in the pig population. Three swine influenza vaccines, two of them commercially available and one experimental, were therefore tested and compared for their efficacy against an H1N1v challenge. One of the commercial vaccines is based on an American classical H1N1 influenza strain, the other is based on a European avian H1N1 influenza strain. The experimental vaccine is based on reassortant virus NYMC X179A (containing the hemagglutinin (HA) and neuraminidase (NA) genes of A/California/7/2009 (H1N1v) and the internal genes of A/Puerto Rico/8/34 (H1N1)). Excretion of infectious virus was reduced by 0.5-3 log(10) by the commercial vaccines, depending on vaccine and sample type. Both vaccines were able to reduce virus replication especially in the lower respiratory tract, with less pathological lesions in vaccinated and subsequently challenged pigs than in unvaccinated controls. In pigs vaccinated with the experimental vaccine, excretion levels of infectious virus in nasal and oropharyngeal swabs, were at or below 1 log(10)TCID(50) per swab and lasted for only 1 or 2 days. An inactivated vaccine containing the HA and NA of an H1N1v is able to protect pigs from an infection with H1N1v, whereas swine influenza vaccines that are currently available are of limited efficaciousness. Whether vaccination of pigs against H1N1v will become opportune remains to be seen and will depend on future evolution of this strain in the pig population. Close monitoring of the pig population, focussing on presence and evolution of

  6. HIV Vaccine Development

    African Journals Online (AJOL)

    Jos, Plateau State, Nigeria. E-Mail: j idoko@yahoo.com. COMMON VACCINE PREVENTABLE. DISEASES: Chicken pox. Hepatitis A. Hepatitis В. Influenza ... ally reversed economic and social development in several countries[3]. Current prevention efforts - including condom education, clean needle distribution, peer ...

  7. Developments in rabies vaccines.

    Science.gov (United States)

    Hicks, D J; Fooks, A R; Johnson, N

    2012-09-01

    The development of vaccines that prevent rabies has a long and distinguished history, with the earliest preceding modern understanding of viruses and the mechanisms of immune protection against disease. The correct application of inactivated tissue culture-derived vaccines is highly effective at preventing the development of rabies, and very few failures are recorded. Furthermore, oral and parenteral vaccination is possible for wildlife, companion animals and livestock, again using inactivated tissue culture-derived virus. However, rabies remains endemic in many regions of the world and causes thousands of human deaths annually. There also remain no means of prophylaxis for rabies once the virus enters the central nervous system (CNS). One reason for this is the poor immune response within the CNS to infection with rabies virus (RABV). New approaches to vaccination using modified rabies viruses that express components of the innate immune system are being applied to this problem. Preliminary reports suggest that direct inoculation of such viruses could trigger an effective anti-viral response and prevent a fatal outcome from RABV infection. © 2012 Crown copyright. Clinical and Experimental Immunology © 2012 British Society for Immunology.

  8. Tuberculosis vaccine development: recent progress.

    Science.gov (United States)

    Orme, I M; McMurray, D N; Belisle, J T

    2001-03-01

    Recent years have seen a renewed effort to develop new vaccines against tuberculosis. As a result, several promising avenues of research have developed, including the production of recombinant vaccines, auxotrophic vaccines, DNA vaccines and subunit vaccines. In this article we briefly review this work, as well as consider the pros and cons of the animal models needed to test these new vaccines. Screening to date has been carried out in mouse and guinea pig models, which have been used to obtain basic information such as the effect of the vaccine on bacterial load, and whether the vaccine can prevent or reduce lung pathology. The results to date lead us to be optimistic that new candidate vaccines could soon be considered for evaluation in clinical trials.

  9. The rotavirus vaccine development pipeline.

    Science.gov (United States)

    Kirkwood, Carl D; Ma, Lyou-Fu; Carey, Megan E; Steele, A Duncan

    2017-04-07

    Rotavirus disease is a leading global cause of mortality and morbidity in children under 5years of age. The effectiveness of the two globally used oral rotavirus vaccines quickly became apparent when introduced into both developed and developing countries, with significant reductions in rotavirus-associated mortality and hospitalizations. However, the effectiveness and impact of the vaccines is reduced in developing country settings, where the burden and mortality is highest. New rotavirus vaccines, including live oral rotavirus candidates and non-replicating approaches continue to be developed, with the major aim to improve the global supply of rotavirus vaccines and for local implementation, and to improve vaccine effectiveness in developing settings. This review provides an overview of the new rotavirus vaccines in development by developing country manufacturers and provides a rationale why newer candidates continue to be explored. It describes the new live oral rotavirus vaccine candidates as well as the non-replicating rotavirus vaccines that are furthest along in development. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  10. Evolutionary genomics of the pandemic 2009 H1N1 influenza viruses (pH1N 1v

    Directory of Open Access Journals (Sweden)

    Song Gang

    2011-05-01

    Full Text Available Abstract Background A new strain of human H1N1 influenza A viruses was broken out in the April 2009 and caused worldwide pandemic emergency. The present study is trying to estimate a temporal reassortment history of 2009 H1N1 viruses by phylogenetic analysis based on a total 394 sequences of H1N1viruses isolated from swine, human and avian. Results Phylogenetic trees of eight gene segments showed that viruses sampled from human formed a well-supported clade, whereas swine and avian lineages were intermixed together. A new divergence swine sublineage containing gene segments of 2009 H1N1 viruses was characterized, which were closely related with swine viruses collected from USA and South Korea during 2004 to 2007 in six segments (PB2, PB1, PA, HA, NP and NS, and to swine viruses isolated from Thailand during 2004 to 2005 in NA and M. Substitution rates were varied drastically among eight segments and the average substitution rate was generally higher in 2009 H1N1 than in swine and human viruses (F2,23 = 5.972, P dN/dS substitution ratios were identified in 2009 H1N1 than in swine and human viruses except M2 gene (F2, 25 = 3.779, P Conclusion Our results implied that at least four reassortments or transmissions probably occurred before 2009 H1N1 viruses. Initial reassortment arose in 1976 and avian-like Eurasian swine viruses emerged. The second transmission happened in Asia and North America between 1988 and 1992, and mostly influenced six segments (PB2, PB1, PA, HA, NP and NS. The third reassortment occurred between North American swine and avian viruses during 1998 to 2000, which involved PB2 and PA segments. Recent reassortments occurred among avian-to-swine reassortant, Eurasian and classical swine viruses during 2004 to 2005. South Korea, Thailand and USA, were identified as locations where reassortments most likely happened. The co-circulation of multiple swine sublineages and special lifestyle in Asia might have facilitated mixing of diverse influenza viruses, leading to generate a novel virus strain.

  11. Development of candidate rotavirus vaccines.

    Science.gov (United States)

    Bishop, R F

    1993-01-01

    Candidate rotavirus vaccines tested to date have been developed using a 'Jennerian' approach. Strains of bovine and simian rotaviruses that are naturally attenuated for humans have been assessed and found to confer immunity that is serotype specific in a varying proportion of recipients. The spectrum of protection has been widened by developing reassortants in which the bovine or simian gene coding for VP7 (the major outer capsid protein) has been replaced by the corresponding gene from human VP7 types 1, 2, 3 or 4. Once the protective antigen(s) are identified it may be possible to develop subunit vaccines that eliminate side effects sometimes observed with live vaccine candidates.

  12. Progress in Brucella vaccine development

    Science.gov (United States)

    YANG, Xinghong; SKYBERG, Jerod A.; CAO, Ling; CLAPP, Beata; THORNBURG, Theresa; PASCUAL, David W.

    2012-01-01

    Brucella spp. are zoonotic, facultative intracellular pathogens, which cause animal and human disease. Animal disease results in abortion of fetuses; in humans, it manifests flu-like symptoms with an undulant fever, with osteoarthritis as a common complication of infection. Antibiotic regimens for human brucellosis patients may last several months and are not always completely effective. While there are no vaccines for humans, several licensed live Brucella vaccines are available for use in livestock. The performance of these animal vaccines is dependent upon the host species, dose, and route of immunization. Newly engineered live vaccines, lacking well-defined virulence factors, retain low residual virulence, are highly protective, and may someday replace currently used animal vaccines. These also have possible human applications. Moreover, due to their enhanced safety and efficacy in animal models, subunit vaccines for brucellosis show great promise for their application in livestock and humans. This review summarizes the progress of brucellosis vaccine development and presents an overview of candidate vaccines. PMID:23730309

  13. Vaccine prophylaxis: achievements, problems, perspectives of development

    Directory of Open Access Journals (Sweden)

    Mavrutenkov V.V.

    2016-09-01

    Full Text Available The article presents medical and social aspects of immune prophylaxis of infectious diseases; the history of vaccines and vaccination is presented, as well as perspectives of development of vaccine prophylaxis.

  14. Clinical malaria vaccine development.

    NARCIS (Netherlands)

    Sauerwein, R.W.

    2009-01-01

    Malaria is a major economic and public health problem in mainly sub-Saharan Africa. Globally 300-500 million new infections occur each year with 1-3 million fatal cases in particular young children. The most effective way to reduce disease and death from infectious diseases is to vaccinate

  15. European Vaccine Initiative: lessons from developing malaria vaccines.

    Science.gov (United States)

    Geels, Mark J; Imoukhuede, Egeruan B; Imbault, Nathalie; van Schooten, Harry; McWade, Terry; Troye-Blomberg, Marita; Dobbelaer, Roland; Craig, Alister G; Leroy, Odile

    2011-12-01

    For over 10 years, the European Vaccine Initiative (EVI; European Malaria Vaccine Initiative until 2009) has contributed to the development of 24 malaria candidate vaccine antigens with 13 vaccine candidates being advanced into Phase I clinical trials, two of which have been transitioned for further clinical development in sub-Saharan Africa. Since its inception the EVI organization has operated as a funding agency, but with a clear service-oriented strategy. The scientific successes and difficulties encountered during these years and how these efforts have led to standardization and harmonization in vaccine development through large-scale European consortia are discussed. In the future, the EVI will remain instrumental in the pharmaceutical and clinical development of vaccines against 'diseases of poverty' with a continued focus on malaria. EVI will continue to focus on funding and managing preclinical evaluation up to Phase I/II clinical trials and strengthening the vaccine-development infrastructure in Europe, albeit with a global orientation.

  16. Vaccine development against Leishmania donovani

    Directory of Open Access Journals (Sweden)

    Amrita eDas

    2012-05-01

    Full Text Available Visceral leishmaniasis (VL caused by Leishmania donovani and Leishmania infantum/ chagasi represents the second most challenging infectious disease worldwide, affecting nearly 500,000 people and 60,000 deaths annually. Zoonotic VL (ZVL caused by L. infantum is re-emergent canid zoonoses which represents a complex epidemiological cycle in New world where domestic dogs serve as reservoir host responsible for potentially fatal human infection where dog culling is the only control measure for eliminating reservoir host. Lifelong immunity in human against reinfection has motivated several attempts in developing prophylactic vaccines against the disease but very few have progressed beyond experimental stage. Absence of any licensed vaccine along with high toxicity and increasing resistance to the current chemotherapeutic drugs has further complicated the situation in endemic regions of the world. Advances in vaccinology, including recombinant proteins, novel antigen-delivery systems/adjuvants, heterologous prime-boost regimens and strategies for intracellular antigen presentation, have contributed to recent advances in vaccine development against VL. Attempts to develop an effective vaccine for use in domestic dogs in areas of canine VL should be pursued for preventing human infection. Studies in animal models and human patients have revealed the pathogenic mechanisms of disease progression and features of protective immunity. This review will summarize the accumulated knowledge about pathogenesis, immune response and prerequisites for protective immunity against human VL. Authors will discuss promising vaccine targets, their developmental status and future prospects in a quest for rational vaccine development against VL. In addition, several challenges such as safety issues, a renewed and coordinated commitment to basic research, preclinical studies and trial design will be addressed to overcome the problems faced in developing effective vaccines

  17. Respiratory syncytial virus vaccine development

    Science.gov (United States)

    Hurwitz, Julia L

    2011-01-01

    Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract viral disease in infants and young children. Presently, there are no explicit recommendations for RSV treatment apart from supportive care. The virus is therefore responsible for an estimated 160,000 deaths per year worldwide. Despite half a century of dedicated research, there remains no licensed vaccine product. Herein are described past and current efforts to harness innate and adaptive immune potentials to combat RSV. A plethora of candidate vaccine products and strategies are reviewed. The development of a successful RSV vaccine may ultimately stem from attention to historical lessons, in concert with an integral partnering of immunology and virology research fields. PMID:21988307

  18. Influenza Vaccines: Unmet Needs and Recent Developments

    Science.gov (United States)

    Noh, Ji Yun

    2013-01-01

    Influenza is a worldwide public health concern. Since the introduction of trivalent influenza vaccine in 1978, vaccination has been the primary means of prevention and control of influenza. Current influenza vaccines have moderate efficacy, good safety, and acceptable tolerability; however, they have unsatisfactory efficacy in older adults, are dependent on egg supply for production, and are time-consuming to manufacture. This review outlines the unmet medical needs of current influenza vaccines. Recent developments in influenza vaccines are also described. PMID:24475351

  19. Development and impact of human papillomavirus vaccines.

    Science.gov (United States)

    Darus, Christopher J; Mueller, Jennifer J

    2013-03-01

    Cervical cancer is a global health crisis that disproportionately affects developing nations and underserved populations. Two vaccines targeting HPV-16 and 18, which account for 70% of invasive cervical carcinomas, are licensed in the United States and numerous countries worldwide. Both vaccine formulations have shown excellent efficacy with minimal toxicity. Numerous questions remain, including cost-effectiveness, vaccination of males, societal acceptance of HPV vaccination, and cervical dysplasia screening in the HPV-immunized population. Access to vaccination for underserved populations both in developed and resource-poor nations remains an issue. Multivalent vaccines that encompass additional oncogenic HPV strains are under development.

  20. Development and trial of vaccines against Brucella

    Science.gov (United States)

    Lalsiamthara, Jonathan

    2017-01-01

    The search for ideal brucellosis vaccines remains active today. Currently, no licensed human or canine anti-brucellosis vaccines are available. In bovines, the most successful vaccine (S19) is only used in calves, as adult vaccination results in orchitis in male, prolonged infection, and possible abortion complications in pregnant female cattle. Another widely deployed vaccine (RB51) has a low protective efficacy. An ideal vaccine should exhibit a safe profile as well as enhance protective efficacy. However, currently available vaccines exhibit one or more major drawbacks. Smooth live attenuated vaccines suffer shortcomings such as residual virulence and serodiagnostic interference. Inactivated vaccines, in general, confer relatively low levels of protection. Recent developments to improve brucellosis vaccines include generation of knockout mutants by targeting genes involved in metabolism, virulence, and the lipopolysaccharide synthesis pathway, as well as generation of DNA vaccines, mucosal vaccines, and live vectored vaccines, have all produced varying degrees of success. Herein, we briefly review the bacteriology, pathogenesis, immunological implications, candidate vaccines, vaccinations, and models related to Brucella. PMID:28859268

  1. Progress in HIV vaccine development.

    Science.gov (United States)

    Hsu, Denise C; O'Connell, Robert J

    2017-05-04

    An HIV-1 vaccine is needed to curtail the HIV epidemic. Only one (RV144) out of the 6 HIV-1 vaccine efficacy trials performed showed efficacy. A potential mechanism of protection is the induction of functional antibodies to V1V2 region of HIV envelope. The 2 main current approaches to the generation of protective immunity are through broadly neutralizing antibodies (bnAb) and induction of functional antibodies (non-neutralizing Abs with other potential anti-viral functions). Passive immunization using bnAb has advanced into phase II clinical trials. The induction of bnAb using mimics of the natural Env trimer or B-cell lineage vaccine design is still in pre-clinical phase. An attempt at optimization of protective functional antibodies will be assessed next with the efficacy trial (HVTN702) about to start. With on-going optimization of prime/boost strategies, the development of mosaic immunogens, replication competent vectors, and emergence of new strategies designed to induce bnAb, the prospects for a preventive HIV vaccine have never been more promising.

  2. [Development of current smallpox vaccines].

    Science.gov (United States)

    Maksiutov, R A; Gavrilova, E V; Shchelkunov, S N

    2011-01-01

    The review gives data on the history of smallpox vaccination and shows the high topicality of designing the current safe vaccines against orthopoxviruses. Four generations of live smallpox, protein subunit, and DNA vaccines are considered. Analysis of the data published leads to the conclusion that it is promising to use the up-to-date generations of safe smallpox subunit or DNA vaccines for mass primary immunization with possible further revaccination with classical live vaccine.

  3. Risk in vaccine research and development quantified.

    Directory of Open Access Journals (Sweden)

    Esther S Pronker

    Full Text Available To date, vaccination is the most cost-effective strategy to combat infectious diseases. Recently, a productivity gap affects the pharmaceutical industry. The productivity gap describes the situation whereby the invested resources within an industry do not match the expected product turn-over. While risk profiles (combining research and development timelines and transition rates have been published for new chemical entities (NCE, little is documented on vaccine development. The objective is to calculate risk profiles for vaccines targeting human infectious diseases. A database was actively compiled to include all vaccine projects in development from 1998 to 2009 in the pre-clinical development phase, clinical trials phase I, II and III up to Market Registration. The average vaccine, taken from the preclinical phase, requires a development timeline of 10.71 years and has a market entry probability of 6%. Stratification by disease area reveals pandemic influenza vaccine targets as lucrative. Furthermore, vaccines targeting acute infectious diseases and prophylactic vaccines have shown to have a lower risk profile when compared to vaccines targeting chronic infections and therapeutic applications. In conclusion; these statistics apply to vaccines targeting human infectious diseases. Vaccines targeting cancer, allergy and autoimmune diseases require further analysis. Additionally, this paper does not address orphan vaccines targeting unmet medical needs, whether projects are in-licensed or self-originated and firm size and experience. Therefore, it remains to be investigated how these - and other - variables influence the vaccine risk profile. Although we find huge differences between the risk profiles for vaccine and NCE; vaccines outperform NCE when it comes to development timelines.

  4. Status of vaccine research and development of vaccines for malaria.

    Science.gov (United States)

    Birkett, Ashley J

    2016-06-03

    Despite recent progress in reducing deaths attributable to malaria, it continues to claim approximately 500,000 lives per year and is associated with approximately 200 million infections. New tools, including safe and effective vaccines, are needed to ensure that the gains of the last 15 years are leveraged toward achieving the ultimate goal of malaria parasite eradication. In 2015, the European Medicines Agency announced the adoption of a positive opinion for the malaria vaccine candidate most advanced in development, RTS,S/AS01, which provides modest protection against clinical malaria; in early 2016, WHO recommended large-scale pilot implementations of RTS,S in settings of moderate-to-high malaria transmission. In alignment with these advancements, the community goals and preferred product characteristics for next-generation vaccines have been updated to inform the development of vaccines that are highly efficacious in preventing clinical malaria, and those needed to accelerate parasite elimination. Next-generation vaccines, targeting all stages of the parasite lifecycle, are in early-stage development with the most advanced in Phase 2 trials. Importantly, progress is being made in the definition of feasible regulatory pathways to accelerate timelines, including for vaccines designed to interrupt transmission of parasites from humans to mosquitoes. The continued absence of financially lucrative, high-income markets to drive investment in malaria vaccine development points to continued heavy reliance on public and philanthropic funding. Copyright © 2016 World Health Organization. Published by Elsevier Ltd.. All rights reserved.

  5. Conjugate Meningococcal Vaccines Development: GSK Biologicals Experience

    Directory of Open Access Journals (Sweden)

    Jacqueline M. Miller

    2011-01-01

    Full Text Available Meningococcal diseases are serious threats to global health, and new vaccines specifically tailored to meet the age-related needs of various geographical areas are required. This paper focuses on the meningococcal conjugate vaccines developed by GSK Biologicals. Two combined conjugate vaccines were developed to help protect infants and young children in countries where the incidence of meningococcal serogroup C or serogroup C and Y disease is important: Hib-MenC-TT vaccine, which offers protection against Haemophilus influenzae type b and Neisseria meningitidis serogroup C diseases, is approved in several countries; and Hib-MenCY-TT vaccine, which adds N. meningitidis serogroup Y antigen, is currently in the final stages of development. Additionally, a tetravalent conjugate vaccine (MenACWY-TT designed to help protect against four meningococcal serogroups is presently being evaluated for global use in all age groups. All of these vaccines were shown to be highly immunogenic and to have clinically acceptable safety profiles.

  6. Recent developments in leishmaniasis vaccine delivery systems.

    Science.gov (United States)

    Bhowmick, Sudipta; Ali, Nahid

    2008-07-01

    The observation that recovery from infection with Leishmania confers immunity to reinfection suggests that control of leishmaniasis by vaccination may be possible. New generation vaccines, particularly those based on recombinant proteins and DNA, are found to be less immunogenic. There is an urgent need for the development of new and improved vaccine adjuvants. Based on their principal mechanisms of action, adjuvants can be broadly separated into two classes: immunostimulatory adjuvants and vaccine delivery systems. Vaccine delivery systems can carry both antigen and adjuvant for effective delivery to the antigen-presenting cells (APCs). In this article, we review the adjuvants, the delivery systems and their combinations used in the search of an effective vaccine against leishmaniasis. Based on current knowledge, cationic liposomes appear to have better prospects as effective delivery systems for developing a vaccine for leishmaniasis.

  7. IMMUNOGENICITY OF ADJUVANT INFLUENZA VACCINE FOR PREGNANT WOMEN

    Directory of Open Access Journals (Sweden)

    M. P. Kostinov

    2017-01-01

    Full Text Available Recent epidemiological events showed that pregnant women are the most vulnerable part of population if there is the flu in the country and they die much more often than the rest part of people. That is why influenza vaccination of population including pregnant women is one of the priorities of public health service in our state. Worldwide experience of influenza vaccination of either adults or children by new adjuvant vaccine has caused our research of its efficiency among pregnant women. The aim of the study was to investigate the level of antibodies to influenza virus strain A/H1N1/v, A/H3N2 and B in pregnant women vaccinated adjuvant trivalent subunit vaccine. Our research is randomized and comparative on parallel groups. It was carried out within the demands of Russian Federation and International ethic norms adapted to such kind of researches. Evaluation of the immunogenicity of the vaccine was conducted in 27 pregnant women in the II trimester of gestation, and in 23 pregnant women in the III trimester of gestation, 19 non-pregnant women was in the control group. The level of antibodies in the serum was determined using a reaction of hemagglutination inhibition before and 1, 3, 6, 9 and 12 months after the vaccination. Revealed that influenza vaccination of pregnant women in the II and III trimester, causes the increase in titers of antibodies to vaccine influenza strains A and B, to fully meet the required criteria CPMP, and does not differ from the nonpregnant group. In a month after vaccination the level of seroprotective against A/H1N1/v was 77.0%, A/H3N2 — 88.9%, B — 85.2% after vaccination in II trimester, and 87.0; 87.0; 91.35% in III trimester of gestation. The factor of seroconversion after vaccination in II trimester for A/H1N1/v was equal to 6.5, A/H3N2 — 7.2, B — 6.5, after vaccination in III trimester of pregnancy: 7.1, 6.5 and 5.1 correspondingly. At the same time revealed accelerated decline in antibody titer against

  8. Nanovaccines: recent developments in vaccination

    Indian Academy of Sciences (India)

    Prakash

    2009-12-04

    Dec 4, 2009 ... of the major binding proteins, and reported that this vaccine could induce mucosal and cellular immunity, and neutralize antibody to various isolates of HIV. These exploratory studies may have implications for viral vaccines. Intranasal delivery of vaccines poses two major challenges: the first is accurate and ...

  9. Vaccine requirements and priorities for developing countries.

    Science.gov (United States)

    Thongcharoen, P

    1986-09-01

    The situation of viral vaccines used in Asian countries is reviewed, focusing on the following vaccines: smallpox, rabies, polio, measles, rubella, mumps, influenza, Japanese encephalitis, hepatitis B, varicella, dengue, and rotavirus. Vaccinations are among the most important strategies to combat communicable diseases caused by bacteria, fungi, parasites, and viruses. Active immunizations are more preferable in most instances than passive ones. It has taken almost 2 centuries to eradicate the highly contagious infection of smallpox from the world. In 1979 the World Health Organization (WHO) announced the global eradication of smallpox. Smallpox vaccination was 1st practiced in 1840 by Dr. Dan Beach Bradley, with the last 2 cases of smallpox reported in Thailand in 1962. Despite the achievement for many years of more ideal rabies vaccine, Semple vaccine continues to be used in developing countries. Attempts should be intensified to produce newer tissue culture vaccines in developing countries themselves and to eradicate vectors. Instances of poliomyelitis were reported in Indonesia, the Philippines, Sri Lanka, India, and Thailand as late as 1983-84, but only a few sporadic cases have occurred in Malaysia since 1980. This mixed record results from polio vaccine having been incorporated into national Expanded Program on Immunization (EPI) programs in many countries. Measles remains 1 of the most common viral infections in children in most developing nations, but morbidity and mortality rates are not accurately obtainable in these countries. Rubella outbreaks have been reported from many countries in Southeast Asia with congenital rubella syndromes due to maternal rubella on the increase in many countries, including Thailand. Children who receive the mumps vaccination are those receiving the combined MMR vaccines. Monovalent mumps vaccine is not obtainable in developing countries. Influenza vaccine is impracticable in most developing countries. Japanese encephalitis

  10. Status of vaccine research and development of vaccines for leishmaniasis.

    Science.gov (United States)

    Gillespie, Portia M; Beaumier, Coreen M; Strych, Ulrich; Hayward, Tara; Hotez, Peter J; Bottazzi, Maria Elena

    2016-06-03

    A number of leishmaniasis vaccine candidates are at various stages of pre-clinical and clinical development. Leishmaniasis is a vector-borne neglected tropical disease (NTD) caused by a protozoan parasite of the genus Leishmania and transmitted to humans by the bite of a sand fly. Visceral leishmaniasis (VL, kala-azar) is a high mortality NTD found mostly in South Asia and East Africa, while cutaneous leishmaniasis (CL) is a disfiguring NTD highly endemic in the Middle East, Central Asia, North Africa, and the Americas. Estimates attribute 50,000 annual deaths and 3.3 million disability-adjusted life years to leishmaniasis. There are only a few approved drug treatments, no prophylactic drug and no vaccine. Ideally, an effective vaccine against leishmaniasis will elicit long-lasting immunity and protect broadly against VL and CL. Vaccines such as Leish-F1, F2 and F3, developed at IDRI and designed based on selected Leishmania antigen epitopes, have been in clinical trials. Other groups, including the Sabin Vaccine Institute in collaboration with the National Institutes of Health are investigating recombinant Leishmania antigens in combination with selected sand fly salivary gland antigens in order to augment host immunity. To date, both VL and CL vaccines have been shown to be cost-effective in economic modeling studies. Copyright © 2016 World Health Organization. Published by Elsevier Ltd.. All rights reserved.

  11. Pharmaceutical companies pledge vaccines for developing countries.

    Science.gov (United States)

    Rovner, J

    2000-03-11

    After the opening of the Millennium Vaccine Initiative (MVI), a program which aims to help lower the toll of infectious disease, four pharmaceutical companies pledge to develop vaccines to fight infectious diseases in the developing world. The agreement by Merck, American Home Products, SmithKline Beecham, and Aventis Pharma came as President Clinton continued to advance the MVI program. Merck announced that it would give 5 million doses of its hepatitis B vaccine over the next 5 years; American Home Products stated that it would donate 10 million doses of its Hemophilus influenzae type b vaccine. Moreover, SmithKline Beecham announced it would do pediatric trials of its malaria vaccine in Africa and renewed a pledge made in 1998 to work with WHO to donate 5 billion doses of albendazole over the next 20 years to eradicate lymphatic filariasis. In addition, Aventis Pharma promised 50 million doses of its polio vaccine for ¿war-torn nations in Africa¿.

  12. The development of flavivirus vaccines | Pulmanausahakul | African ...

    African Journals Online (AJOL)

    Vaccine development to eliminate flaviviral infections has been marked by uneven progress and a large number of setbacks. To date, no single approach has proved successful in leading to vaccine development against a wide range of flaviviruses, but the application of modern techniques to the problem is opening up new ...

  13. Development of Novel Vaccines against Enterovirus-71

    Directory of Open Access Journals (Sweden)

    Pinn Tsin Isabel Yee

    2015-12-01

    Full Text Available The hand, foot and mouth disease is caused by a group of Enteroviruses such as Enterovirus 71 (EV-A71 and Coxsackievirus CV-A5, CV-A8, and CV-A16. Mild symptoms of EV-A71 infection in children range from high fever, vomiting, rashes and ulcers in mouth but can produce more severe symptoms such as brainstem and cerebellar encephalitis, leading up to cardiopulmonary failure and death. The lack of vaccines and antiviral drugs against EV-A71 highlights the urgency of developing preventive and treatment agents against EV-A71 to prevent further fatalities. Research groups have developed experimental inactivated vaccines, recombinant Viral Protein 1 (VP1 vaccine and virus-like particles (VLPs. The inactivated EV-A71 vaccine is considered the safest viral vaccine, as there will be no reversion to the infectious wild type strain. The recombinant VP1 vaccine is a cost-effective immunogen, while VLPs contain an arrangement of epitopes that can elicit neutralizing antibodies against the virus. As each type of vaccine has its advantages and disadvantages, increased studies are required in the development of such vaccines, whereby high efficacy, long-lasting immunity, minimal risk to those vaccinated, safe and easy production, low cost, dispensing the need for refrigeration and convenient delivery are the major goals in their design.

  14. Nanovaccines: recent developments in vaccination

    Indian Academy of Sciences (India)

    In the past 100 years, vaccination has contributed immensely to public health by preventing a number of infectious diseases. Attenuated, killed or part of the microorganism is employed to stimulate the immune system against it. Progress in biotechnology has provided protective immunity through DNA vaccines. In recent ...

  15. DENGUE VACCINE, CHALLENGES, DEVELOPMENT AND STRATEGIES

    Directory of Open Access Journals (Sweden)

    Dewi Marbawati

    2014-08-01

    Full Text Available ABSTRAKPenyakit demam Dengue endemik di lebih dari 100 negara di dunia. Obat anti virus Dengue efektif belum ditemukan danpengendalian vektor dinilai kurang efektif, sehingga diperlukan upaya pencegahan dengan vaksinasi. Vaksin Dengue yangideal adalah murah, mencakup 4 serotipe, efektif dalam memberikan kekebalan, cukup diberikan sekali seumur hidup, aman,memberi kekebalan jangka panjang, stabil dalam penyimpanan dan stabil secara genetis (tidak bermutasi. Beberapakandidat vaksin yang telah dan sedang dikembangkan oleh para peneliti di seluruh dunia adalah tetravalent live attenuatedvaccine, vaksin Chimera (ChimeriVax, vaksin subunit dan vaksin DNA. Vaksin Dengue dipandang sebagai pendekatan yangefektif dan berkesinambungan dalam mengendalikan penyakit Dengue. Tahun 2003 telah terbentuk Pediatric DengueVaccine Initiative (PDVI, yaitu sebuah konsorsium internasional yang bergerak dalam advokasi untuk meyakinkanmasyarakat internasional akan penting dan mendesaknya vaksin Dengue. Konsorsium vaksin Dengue Indonesia saat iniberupaya mengembangkan vaksin Dengue dengan menggunakan strain virus lokal.Kata kunci: Dengue, virus, vaksinABSTRACTDengue fever is endemic in more than 100 countries in the world. The effective dengue antiviral drug has not been found yet,and vector control is considered less effective. Prevention program by vaccination is needed. An ideal dengue vaccine shouldbe inexpensive, covering four serotypes (tetravalent, effective in providing immunity, given once a lifetime, safe, stable instorage and genetically. Several vaccine candidates have been and are being developed included attenuated tetravalentvaccine, ChimeriVax, sub- unit vaccines and DNA vaccines. Dengue vaccine is seen as an effective and sustainable approachto controll Dengue infection. In 2003, Pediatric Dengue Vaccine Initiative (PDVI has been formed as an internationalconsortium involved in advocacy to convince the international community about the essence and urgency

  16. Human capital gaps in vaccine development: an issue for global vaccine development and global health.

    Science.gov (United States)

    Cawein, Andrea; Emini, Emilio; Watson, Michael; Dailey, Joanna; Donnelly, John; Tresnan, Dina; Evans, Tom; Plotkin, Stanley; Gruber, William

    2017-05-01

    Despite the success of vaccines in reducing the morbidity and mortality associated with infectious diseases, many infectious diseases, both newly emerging and well known, lack vaccines. The global capability for beginning-to-end vaccine development has become limited, primarily owing to a scarcity of human capital necessary to guide the development of novel vaccines from the laboratory to the marketplace. Here, we identify and discuss the gaps in human capital necessary for robust vaccine development and make recommendations to begin to address these deficiencies. © 2017 New York Academy of Sciences.

  17. A history of hookworm vaccine development.

    Science.gov (United States)

    Schneider, Brent; Jariwala, Amar R; Periago, Maria Victoria; Gazzinelli, Maria Flávia; Bose, Swaroop N; Hotez, Peter J; Diemert, David J; Bethony, Jeffrey M

    2011-11-01

    The human hookworms Necator americanus and Ancylostoma duodenale remain among the most common infections of humans in areas of rural poverty in the developing regions of the world, with an estimated 1 billion people infected with one or more of these parasites. Herein, we review the nearly 100 years of research, development, animal testing, and fieldwork that have led to our current progress in recombinant hookworm vaccines. We begin with the identification of hookworm at the start of the 20th century in Southern US, then discuss the progress in developed countries to eliminate human hookworm infection, and then the industrial development and field use in the 1970s a canine hookworm vaccine(Ancylostoma caninum), and finally our progress to date in the development and clinical testing of an array of recombinant antigens to prevent human hookworm disease from N. americanus infection. Special attention is given to the challenges faced in the development of a vaccine against a blood-feeding nematode, including the epidemiology of infection (high prevalence of infection), pathogenesis (chronic infection that increases with the age of the host), and a robust immune response that fails to confer the protection in the host and a concomitant absence of correlates of protection by a successful vaccine could be developed and tested. Finally, we provide the optimal and acceptable profiles of a human hookworm vaccine, including the proposed indication, target population, and route of administration, as developed by the Human Hookworm Vaccine Initiative, the only group currently working on vaccines targeting this parasite.

  18. Nonclinical Development of BCG Replacement Vaccine Candidates

    Directory of Open Access Journals (Sweden)

    Bernd Eisele

    2013-04-01

    Full Text Available The failure of current Mycobacterium bovis bacille Calmette–Guérin (BCG vaccines, given to neonates to protect against adult tuberculosis and the risk of using these live vaccines in HIV-infected infants, has emphasized the need for generating new, more efficacious and safer replacement vaccines. With the availability of genetic techniques for constructing recombinant BCG (rBCG strains containing well-defined gene deletions or insertions, new vaccine candidates are under evaluation at both the preclinical and clinical stages of development. Since most BCG vaccines in use today were evaluated in clinical trials decades ago and are produced by outdated processes, the development of new BCG vaccines offers a number of advantages that include a modern well-defined manufacturing process along with state-of-the-art evaluation of safety and efficacy in target populations. We provide a description of the preclinical development of two novel rBCGs, VPM1002 that was constructed by adding a modified hly gene coding for the protein listeriolysin O (LLO from Listeria monocytogenes and AERAS-422, which carries a modified pfoA gene coding for the protein perfringolysin O (PFO from Clostridium perfringens, and three genes from Mycobacterium tuberculosis. Novel approaches like these should be helpful in generating stable and effective rBCG vaccine candidates that can be better characterized than traditional BCG vaccines.

  19. Nonclinical Development of BCG Replacement Vaccine Candidates.

    Science.gov (United States)

    Velmurugan, Kamalakannan; Grode, Leander; Chang, Rosemary; Fitzpatrick, Megan; Laddy, Dominick; Hokey, David; Derrick, Steven; Morris, Sheldon; McCown, David; Kidd, Reginald; Gengenbacher, Martin; Eisele, Bernd; Kaufmann, Stefan H E; Fulkerson, John; Brennan, Michael J

    2013-04-16

    The failure of current Mycobacterium bovis bacille Calmette-Guérin (BCG) vaccines, given to neonates to protect against adult tuberculosis and the risk of using these live vaccines in HIV-infected infants, has emphasized the need for generating new, more efficacious and safer replacement vaccines. With the availability of genetic techniques for constructing recombinant BCG (rBCG) strains containing well-defined gene deletions or insertions, new vaccine candidates are under evaluation at both the preclinical and clinical stages of development. Since most BCG vaccines in use today were evaluated in clinical trials decades ago and are produced by outdated processes, the development of new BCG vaccines offers a number of advantages that include a modern well-defined manufacturing process along with state-of-the-art evaluation of safety and efficacy in target populations. We provide a description of the preclinical development of two novel rBCGs, VPM1002 that was constructed by adding a modified hly gene coding for the protein listeriolysin O (LLO) from Listeria monocytogenes and AERAS-422, which carries a modified pfoA gene coding for the protein perfringolysin O (PFO) from Clostridium perfringens, and three genes from Mycobacterium tuberculosis. Novel approaches like these should be helpful in generating stable and effective rBCG vaccine candidates that can be better characterized than traditional BCG vaccines.

  20. Progress and controversies in developing cancer vaccines

    Directory of Open Access Journals (Sweden)

    Speiser Daniel E

    2005-04-01

    Full Text Available Abstract Immunotherapy has become a standard approach for cancer management, through the use of cytokines (eg: interleukin-2 and monoclonal antibodies. Cancer vaccines hold promise as another form of immunotherapy, and there has been substantial progress in identifying shared antigens recognized by T cells, in developing vaccine approaches that induce antigen-specific T cell responses in cancer patients, and in developing new technology for monitoring immune responses in various human tissue compartments. Dramatic clinical regressions of human solid tumors have occurred with some cancer vaccines, but the rate of those responses remains low. This article is part of a 2-part point:counterpoint series on peptide vaccines and adoptive therapy approaches for cancer. The current status of cancer vaccination, and associated challenges, are discussed. Emphasis is placed on the need to increase our knowledge of cancer immunobiology, as well as to improve monitoring of cellular immune function after vaccination. Progress in both areas will facilitate development of effective cancer vaccines, as well as of adoptive therapy. Effective cancer vaccines promise to be useful for treatment and prevention of cancer at low cost and with low morbidity.

  1. Malnutrition and vaccination in developing countries

    Science.gov (United States)

    Prendergast, Andrew J.

    2015-01-01

    Malnutrition contributes to an estimated 45% of deaths among children under 5 years of age in developing countries, predominantly due to infections. Malnourished children therefore stand to benefit hugely from vaccination, but malnutrition has been described as the most common immunodeficiency globally, suggesting that they may not be able to respond effectively to vaccines. The immunology of malnutrition remains poorly characterized, but is associated with impairments in mucosal barrier integrity, and innate and adaptive immune dysfunction. Despite this, the majority of malnourished children can mount a protective immune response following vaccination, although the timing, quality and duration of responses may be impaired. This paper reviews the evidence for vaccine immunogenicity in malnourished children, discusses the importance of vaccination in prevention of malnutrition and highlights evidence gaps in our current knowledge. PMID:25964453

  2. Recombinant vaccines and the development of new vaccine strategies

    Energy Technology Data Exchange (ETDEWEB)

    Nascimento, I.P.; Leite, L.C.C. [Centro de Biotecnologia, Instituto Butantan, São Paulo, SP (Brazil)

    2012-09-07

    Vaccines were initially developed on an empirical basis, relying mostly on attenuation or inactivation of pathogens. Advances in immunology, molecular biology, biochemistry, genomics, and proteomics have added new perspectives to the vaccinology field. The use of recombinant proteins allows the targeting of immune responses focused against few protective antigens. There are a variety of expression systems with different advantages, allowing the production of large quantities of proteins depending on the required characteristics. Live recombinant bacteria or viral vectors effectively stimulate the immune system as in natural infections and have intrinsic adjuvant properties. DNA vaccines, which consist of non-replicating plasmids, can induce strong long-term cellular immune responses. Prime-boost strategies combine different antigen delivery systems to broaden the immune response. In general, all of these strategies have shown advantages and disadvantages, and their use will depend on the knowledge of the mechanisms of infection of the target pathogen and of the immune response required for protection. In this review, we discuss some of the major breakthroughs that have been achieved using recombinant vaccine technologies, as well as new approaches and strategies for vaccine development, including potential shortcomings and risks.

  3. Recombinant vaccines and the development of new vaccine strategies

    Directory of Open Access Journals (Sweden)

    I.P. Nascimento

    2012-12-01

    Full Text Available Vaccines were initially developed on an empirical basis, relying mostly on attenuation or inactivation of pathogens. Advances in immunology, molecular biology, biochemistry, genomics, and proteomics have added new perspectives to the vaccinology field. The use of recombinant proteins allows the targeting of immune responses focused against few protective antigens. There are a variety of expression systems with different advantages, allowing the production of large quantities of proteins depending on the required characteristics. Live recombinant bacteria or viral vectors effectively stimulate the immune system as in natural infections and have intrinsic adjuvant properties. DNA vaccines, which consist of non-replicating plasmids, can induce strong long-term cellular immune responses. Prime-boost strategies combine different antigen delivery systems to broaden the immune response. In general, all of these strategies have shown advantages and disadvantages, and their use will depend on the knowledge of the mechanisms of infection of the target pathogen and of the immune response required for protection. In this review, we discuss some of the major breakthroughs that have been achieved using recombinant vaccine technologies, as well as new approaches and strategies for vaccine development, including potential shortcomings and risks.

  4. Mucosal Vaccine Development Based on Liposome Technology.

    Science.gov (United States)

    Bernasconi, Valentina; Norling, Karin; Bally, Marta; Höök, Fredrik; Lycke, Nils Y

    2016-01-01

    Immune protection against infectious diseases is most effective if located at the portal of entry of the pathogen. Hence, there is an increasing demand for vaccine formulations that can induce strong protective immunity following oral, respiratory, or genital tract administration. At present, only few mucosal vaccines are found on the market, but recent technological advancements and a better understanding of the principles that govern priming of mucosal immune responses have contributed to a more optimistic view on the future of mucosal vaccines. Compared to live attenuated vaccines, subcomponent vaccines, most often protein-based, are considered safer, more stable, and less complicated to manufacture, but they require the addition of nontoxic and clinically safe adjuvants to be effective. In addition, another limiting factor is the large antigen dose that usually is required for mucosal vaccines. Therefore, the combination of mucosal adjuvants with the recent progress in nanoparticle technology provides an attractive solution to these problems. In particular, the liposome technology is ideal for combining protein antigen and adjuvant into an effective mucosal vaccine. Here, we describe and discuss recent progress in nanoparticle formulations using various types of liposomes that convey strong promise for the successful development of the next generation of mucosal vaccines.

  5. Vaccines in development against West Nile virus.

    Science.gov (United States)

    Brandler, Samantha; Tangy, Frederic

    2013-09-30

    West Nile encephalitis emerged in 1999 in the United States, then rapidly spread through the North American continent causing severe disease in human and horses. Since then, outbreaks appeared in Europe, and in 2012, the United States experienced a new severe outbreak reporting a total of 5,387 cases of West Nile virus (WNV) disease in humans, including 243 deaths. So far, no human vaccine is available to control new WNV outbreaks and to avoid worldwide spreading. In this review, we discuss the state-of-the-art of West Nile vaccine development and the potential of a novel safe and effective approach based on recombinant live attenuated measles virus (MV) vaccine. MV vaccine is a live attenuated negative-stranded RNA virus proven as one of the safest, most stable and effective human vaccines. We previously described a vector derived from the Schwarz MV vaccine strain that stably expresses antigens from emerging arboviruses, such as dengue, West Nile or chikungunya viruses, and is strongly immunogenic in animal models, even in the presence of MV pre-existing immunity. A single administration of a recombinant MV vaccine expressing the secreted form of WNV envelope glycoprotein elicited protective immunity in mice and non-human primates as early as two weeks after immunization, indicating its potential as a human vaccine.

  6. The Development of an AIDS Mucosal Vaccine

    Directory of Open Access Journals (Sweden)

    Xian Tang

    2010-01-01

    Full Text Available It is well known that mucosal tissues contain the largest surface area of the human body and are the front line of natural host defense against various pathogens. In fact, more than 80% of infectious disease pathogens probably gain entry into the susceptible human hosts through open mucosal surfaces. Human immunodeficiency virus type one (HIV-1, a mainly sexually transmitted virus, also primarily targets the vaginal and gastrointestinal mucosa as entry sites for viral transmission, seeding, replication and amplification. Since HIV-1 establishes its early replication in vaginal or rectal mucosal tissues, the induction of sufficient mucosal immunity at the initial site of HIV-1 transmission becomes essential for a protective vaccine. However, despite the fact that current conventional vaccine strategies have remained unsuccessful in preventing HIV-1 infection, sufficient financial support and resources have yet to be given to develop a vaccine able to elicit protective mucosal immunity against sexual transmissions. Interestingly, Chinese ancestors invented variolation through intranasal administration about one thousand years ago, which led to the discovery of a successful smallpox vaccine and the final eradication of the disease. It is the hope for all mankind that the development of a mucosal AIDS vaccine will ultimately help control the AIDS pandemic. In order to discover an effective mucosal AIDS vaccine, it is necessary to have a deep understanding of mucosal immunology and to test various mucosal vaccination strategies.

  7. New approaches to HIV vaccine development.

    Science.gov (United States)

    Haynes, Barton F

    2015-08-01

    Development of a safe and effective vaccine for HIV is a major global priority. However, to date, efforts to design an HIV vaccine with methods used for development of other successful viral vaccines have not succeeded due to HIV diversity, HIV integration into the host genome, and ability of HIV to consistently evade anti-viral immune responses. Recent success in isolation of potent broadly neutralizing antibodies (bnAbs), in discovery of mechanisms of bnAb induction, and in discovery of atypical mechanisms of CD8T cell killing of HIV-infected cells, have opened new avenues for strategies for HIV vaccine design. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Development of Globo-H cancer vaccine.

    Science.gov (United States)

    Danishefsky, Samuel J; Shue, Youe-Kong; Chang, Michael N; Wong, Chi-Huey

    2015-03-17

    The development of anticancer vaccines requires the identification of unique epitope markers, preferably expressed exclusively on the surface of cancer cells. This Account describes the path of development of a carbohydrate-based vaccine for metastatic breast cancer, including the selection and synthesis of Globo-H as the target, the development of the vaccine conjugate and adjuvant design, the study of the immune response and consideration of class switch, and the analysis of Globo-H distribution on the surface of various cancer cells, cancer stem cells, and normal cells. The first synthesis of Globo-H was accomplished through the use of glycal chemistry; this approach delivered sufficient material for evaluation in phase I human trials. The development of a programmable one-pot synthesis method rendered the synthesis more practical and enabled the midstage proof-of-concept phase II trial and late-stage phase III trial. Finally, enzymatic synthesis of Globo-H coupled with cofactor regeneration was used for the late-stage multicenter trials and manufacture of the product. Along this path of development, it was discovered that the vaccine induced antibodies to target not only Globo-H, but also SSEA3 and SSEA4. Moreover, these three glycolipids were found to be uniquely expressed not only on the cell surface of breast cancer but on 15 additional cancer types, suggesting the broad application of this vaccine in cancer treatment and perhaps cancer prevention. In addition, a new glycolipid adjuvant was designed to target the CD1d receptor on dendritic cells and B cells for presentation to and activation of T cells to modulate the immune response and induce a class switch from IgM to IgG, thereby overcoming the common problem of carbohydrate-based vaccines that often induce mainly IgM antibodies. As demonstrated in this vaccine development, the chemical approach to the synthesis and conjugation of carbohydrate-based immunogens provides the flexibility for access to

  9. Non-influenza viruses in acute respiratory infections among young children. High prevalence of HMPV during the H1N1V.2009 pandemic in Poland.

    Science.gov (United States)

    Pancer, Katarzyna W; Gut, Włodzimierz; Abramczuk, Edyta; Lipka, Bożena; Litwińska, Bogumiła

    2014-01-01

    In Poland the majority of hospitalized cases of pneumonia (annually more than 70000) were reported without determination of an aetiological agent (J18 of ICD-10), also because diagnosis of viral ARTI is limited to identification of influenza viruses or sometimes RSV. For determination the contribution of non-influenza viruses in ARTI among children, 381 nasopharyngeal swabs from hospitalized in period X.2008-IV.2011y. children (aged 1 day - 5 y.o.) were tested for RSV, HMPV, HEV/HRV, HPIV 1-3, HAdV, HBoV. At least one viral agent was detected in 72.7% of patients. The most predominant was RSV infection (49%), followed by HEV/HRV (15.5%); HMPV (8.7%), Adenoviruses (7.4%), HPIVt.1-3 (5.8%) and HBoV (5.5%). Seven periods based on the median of examined children/month were determined: 3 with increased number of ARTI. RSV infections, diagnosed in all periods, were predominate in five periods, mainly in LRTI cases. In the 3th period - HMPV was predominant, in the 5th - HEV/HRV. It was found that clinical manifestation of HMPV infections varied depending on the period. Relatively high prevalence of HBoV or HMPV cases of ARTI, especially different clinical picture in some periods (ARTI without pneumonia or bronchiolitis), indicated necessary of more detailed molecular and epidemiological studies. Also our results indicate the need for improved diagnostic capabilities of virological tests in acute upper and lower respiratory tract infections in children.

  10. Zika Vaccine Development: Flavivirus Foils

    Science.gov (United States)

    2016-09-01

    be transmitted sexually and its association with microcephaly 25-27. Methodical evaluation and open discourse regarding potential safety risks is... disease associated with it are significantly more problematic for the vast majority of infected patients than is Zika virus infection. Infection with...imperative, particularly considering that women of child-bearing age and pregnant women may be primary recipients of the vaccine. In this

  11. Liposomal adjuvant development for leishmaniasis vaccines.

    Science.gov (United States)

    Askarizadeh, Anis; Jaafari, Mahmoud Reza; Khamesipour, Ali; Badiee, Ali

    2017-08-01

    Leishmaniasis is a parasitic disease that ranges in severity from skin lesions to fatality. Since long-lasting protection is induced upon recovery from cutaneous leishmaniasis, development of an effective vaccine is promising. However, there is no vaccine for use in humans yet. It seems limited efficacy in leishmaniasis vaccines is due to lack of an appropriate adjuvant or delivery system. Hence, the use of particulate adjuvants such as liposomes for effective delivery to the antigen presenting cells (APCs) is a valuable strategy to enhance leishmaniasis vaccine efficacy. The extraordinary versatility of liposomes because of their unique amphiphilic and biphasic nature allows for using antigens or immunostimulators within the core, on the surface or within the bilayer, and modulates both the magnitude and the T-helper bias of the immune response. In this review article, we attempt to summarize the role of liposomal adjuvants in the development of Leishmania vaccines and describe the main physicochemical properties of liposomes like phospholipid composition, surface charge, and particle size during formulation design. We also suggest potentially useful formulation strategies in order for future experiments to have a chance to succeed as liposomal vaccines against leishmaniasis.

  12. Development of Stable Influenza Vaccine Powder Formulations: Challenges and Possibilities

    Science.gov (United States)

    Amorij, J-P.; Huckriede, A.; Wilschut, J.; Frijlink, H. W.

    2008-01-01

    Influenza vaccination represents the cornerstone of influenza prevention. However, today all influenza vaccines are formulated as liquids that are unstable at ambient temperatures and have to be stored and distributed under refrigeration. In order to stabilize influenza vaccines, they can be brought into the dry state using suitable excipients, stabilizers and drying processes. The resulting stable influenza vaccine powder is independent of cold-chain facilities. This can be attractive for the integration of the vaccine logistics with general drug distribution in Western as well as developing countries. In addition, a stockpile of stable vaccine formulations of potential vaccines against pandemic viruses can provide an immediate availability and simple distribution of vaccine in a pandemic outbreak. Finally, in the development of new needle-free dosage forms, dry and stable influenza vaccine powder formulations can facilitate new or improved targeting strategies for the vaccine compound. This review represents the current status of dry stable inactivated influenza vaccine development. Attention is given to the different influenza vaccine types (i.e. whole inactivated virus, split, subunit or virosomal vaccine), the rationale and need for stabilized influenza vaccines, drying methods by which influenza vaccines can be stabilized (i.e. lyophilization, spray drying, spray-freeze drying, vacuum drying or supercritical fluid drying), the current status of dry influenza vaccine development and the challenges for ultimate market introduction of a stable and effective dry-powder influenza vaccine. PMID:18338241

  13. Development of vaccines for Plasmodium vivax malaria.

    Science.gov (United States)

    Mueller, Ivo; Shakri, Ahmad Rushdi; Chitnis, Chetan E

    2015-12-22

    Plasmodium vivax continues to cause significant morbidity outside Africa with more than 50% of malaria cases in many parts of South and South-east Asia, Pacific islands, Central and South America being attributed to P. vivax infections. The unique biology of P. vivax, including its ability to form latent hypnozoites that emerge months to years later to cause blood stage infections, early appearance of gametocytes before clinical symptoms are apparent and a shorter development cycle in the vector makes elimination of P. vivax using standard control tools difficult. The availability of an effective vaccine that provides protection and prevents transmission would be a valuable tool in efforts to eliminate P. vivax. Here, we review the latest developments related to P. vivax malaria vaccines and discuss the challenges as well as directions toward the goal of developing highly efficacious vaccines against P. vivax malaria. Copyright © 2015. Published by Elsevier Ltd.

  14. Vaccine development for emerging virulent infectious diseases.

    Science.gov (United States)

    Maslow, Joel N

    2017-10-04

    The recent outbreak of Zaire Ebola virus in West Africa altered the classical paradigm of vaccine development and that for emerging infectious diseases (EIDs) in general. In this paper, the precepts of vaccine discovery and advancement through pre-clinical and clinical assessment are discussed in the context of the recent Ebola virus, Middle East Respiratory Syndrome coronavirus (MERS-CoV), and Zika virus outbreaks. Clinical trial design for diseases with high mortality rates and/or high morbidity in the face of a global perception of immediate need and the factors that drive design in the face of a changing epidemiology are presented. Vaccines for EIDs thus present a unique paradigm to standard development precepts. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Development of Vaccines for Chikungunya Fever.

    Science.gov (United States)

    Erasmus, Jesse H; Rossi, Shannan L; Weaver, Scott C

    2016-12-15

    Chikungunya fever, an acute and often chronic arthralgic disease caused by the mosquito-borne chikungunya virus (CHIKV), has reemerged since 2004 to cause millions of cases. Because CHIKV exhibits limited antigenic diversity and is not known to be capable of reinfection, a vaccine could serve to both prevent disease and diminish human amplification during epidemic circulation. Here, we review the many promising vaccine platforms and candidates developed for CHIKV since the 1970s, including several in late preclinical or clinical development. We discuss the advantages and limitations of each, as well as the commercial and regulatory challenges to bringing a vaccine to market. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  16. Development of Burkholderia mallei and pseudomallei vaccines.

    Science.gov (United States)

    Silva, Ediane B; Dow, Steven W

    2013-01-01

    Burkholderia mallei and Burkholderia pseudomallei are Gram-negative bacteria that cause glanders and melioidosis, respectively. Inhalational infection with either organism can result in severe and rapidly fatal pneumonia. Inoculation by the oral and cutaneous routes can also produce infection. Chronic infection may develop after recovery from acute infection with both agents, and control of infection with antibiotics requires prolonged treatment. Symptoms for both meliodosis and glanders are non-specific, making diagnosis difficult. B. pseudomallei can be located in the environment, but in the host, B. mallei and B. psedomallei are intracellular organisms, and infection results in similar immune responses to both agents. Effective early innate immune responses are critical to controlling the early phase of the infection. Innate immune signaling molecules such as TLR, NOD, MyD88, and pro-inflammatory cytokines such as IFN-γ and TNF-α play key roles in regulating control of infection. Neutrophils and monocytes are critical cells in the early infection for both microorganisms. Both monocytes and macrophages are necessary for limiting dissemination of B. pseudomallei. In contrast, the role of adaptive immune responses in controlling Burkholderia infection is less well understood. However, T cell responses are critical for vaccine protection from Burkholderia infection. At present, effective vaccines for prevention of glanders or meliodosis have not been developed, although recently development of Burkholderia vaccines has received renewed attention. This review will summarize current and past approaches to develop B. mallei and B. pseudomalllei vaccines, with emphasis on immune mechanisms of protection and the challenges facing the field. At present, immunization with live attenuated bacteria provides the most effective and durable immunity, and it is important therefore to understand the immune correlates of protection induced by live attenuated vaccines. Subunit

  17. Development of Burkholderia mallei and pseudomallei vaccines

    Science.gov (United States)

    Silva, Ediane B.; Dow, Steven W.

    2013-01-01

    Burkholderia mallei and Burkholderia pseudomallei are Gram-negative bacteria that cause glanders and melioidosis, respectively. Inhalational infection with either organism can result in severe and rapidly fatal pneumonia. Inoculation by the oral and cutaneous routes can also produce infection. Chronic infection may develop after recovery from acute infection with both agents, and control of infection with antibiotics requires prolonged treatment. Symptoms for both meliodosis and glanders are non-specific, making diagnosis difficult. B. pseudomallei can be located in the environment, but in the host, B. mallei and B. psedomallei are intracellular organisms, and infection results in similar immune responses to both agents. Effective early innate immune responses are critical to controlling the early phase of the infection. Innate immune signaling molecules such as TLR, NOD, MyD88, and pro-inflammatory cytokines such as IFN-γ and TNF-α play key roles in regulating control of infection. Neutrophils and monocytes are critical cells in the early infection for both microorganisms. Both monocytes and macrophages are necessary for limiting dissemination of B. pseudomallei. In contrast, the role of adaptive immune responses in controlling Burkholderia infection is less well understood. However, T cell responses are critical for vaccine protection from Burkholderia infection. At present, effective vaccines for prevention of glanders or meliodosis have not been developed, although recently development of Burkholderia vaccines has received renewed attention. This review will summarize current and past approaches to develop B. mallei and B. pseudomalllei vaccines, with emphasis on immune mechanisms of protection and the challenges facing the field. At present, immunization with live attenuated bacteria provides the most effective and durable immunity, and it is important therefore to understand the immune correlates of protection induced by live attenuated vaccines. Subunit

  18. Development of Vaccines Against Nocardiosis in Fishes.

    Science.gov (United States)

    Nayak, Sukanta K; Nakanishi, Teruyuki

    2016-01-01

    Nocardiosis, one of the most systemic and devastating diseases, is currently emerging as an important disease of cultured marine and freshwater fishes. The causative agent of this disease is Nocardia seriolae, a Gram-positive acid-fast bacterium. An effective vaccine/vaccination strategy against this pathogen is necessary to control the significant loss in aquaculture practices. In this chapter, we present the vaccination/immunization protocol in fish against both live (sublethal) and inactivated form of N. seriolae using ginbuna crucian carp (Carassius auratus langsdorfii) as a model. N. seriolae either in live (sublethal) form or inactivated antigenic form is found to elevate immunity in ginbuna and also can induce protective immunity upon challenge. In order to develop live vaccine, determination of sublethal dose is critical and needs to be established in the host fish species through pathogenicity and persistence studies. Herein for ginbuna, a sublethal dose of 10(6) CFU/mL was determined by pathogenicity study through a series of challenge doses followed by pathogen persistence study by microbiological and molecular techniques. On the other hand, for inactivated antigenic form, the concentration of the N. seriolae was approximately 10(8) CFU/mL. Although this study showed significant potential of both the forms of N. seriolae as candidate for vaccination, factors such as dose, duration and form need to be optimized in individual fish species.

  19. Bovine rotavirus pentavalent vaccine development in India.

    Science.gov (United States)

    Zade, Jagdish K; Kulkarni, Prasad S; Desai, Sajjad A; Sabale, Rajendra N; Naik, Sameer P; Dhere, Rajeev M

    2014-08-11

    A bovine rotavirus pentavalent vaccine (BRV-PV) containing rotavirus human-bovine (UK) reassortant strains of serotype G1, G2, G3, G4 and G9 has been developed by the Serum Institute of India Ltd, in collaboration with the National Institute of Allergy and Infectious Diseases (NIAID), USA. The vaccine underwent animal toxicity studies and Phase I and II studies in adults, toddlers and infants. It has been found safe and immunogenic and will undergo a large Phase III study to assess efficacy against severe rotavirus gastroenteritis. Copyright © 2014. Published by Elsevier Ltd.

  20. Impact of BRICS' investment in vaccine development on the global vaccine market.

    Science.gov (United States)

    Kaddar, Miloud; Milstien, Julie; Schmitt, Sarah

    2014-06-01

    Brazil, the Russian Federation, India, China and South Africa--the countries known as BRICS--have made considerable progress in vaccine production, regulation and development over the past 20 years. In 1993, all five countries were producing vaccines but the processes used were outdated and non-standardized, there was little relevant research and there was negligible international recognition of the products. By 2014, all five countries had strong initiatives for the development of vaccine technology and had greatly improved their national regulatory capacity. South Africa was then the only BRICS country that was not completely producing vaccines. South Africa is now in the process of re-establishing its own vaccine production and passing beyond the stage of simply importing, formulating and filling vaccine bulks. Changes in the public sector's price per dose of selected vaccines, the global market share represented by products from specific manufacturers, and the attractiveness, for multinational companies, of partnership and investment opportunities in BRICS companies have all been analysed. The results indicate that the BRICS countries have had a major impact on vaccine price and availability, with much of that impact attributable to the output of Indian vaccine manufacturers. China is expected to have a greater impact soon, given the anticipated development of Chinese vaccine manufacturers in the near future. BRICS' accomplishments in the field of vaccine development are expected to reshape the global vaccine market and accelerate access to vaccines in the developing world. The challenge is to turn these expectations into strategic actions and practical outcomes.

  1. Vaccine victory | IDRC - International Development Research Centre

    International Development Research Centre (IDRC) Digital Library (Canada)

    2017-05-31

    May 31, 2017 ... A Canadian virologist created a breakthrough five-in-one livestock vaccine that could transform the lives of millions in Africa and beyond. Part of an ongoing series of stories about innovative projects in the developing world, a partnership between IDRC and Canadian Geographic. Read the full story Visit ...

  2. Development of orphan vaccines: an industry perspective.

    Science.gov (United States)

    Lang, J; Wood, S C

    1999-01-01

    The development of vaccines against rare emerging infectious diseases is hampered by many disincentives. In the face of growing in-house expenditures associated with research and development projects in a complex legal and regulatory environment, most pharmaceutical companies prioritize their projects and streamline their product portfolio. Nevertheless, for humanitarian reasons, there is a need to develop niche vaccines for rare diseases not preventable or curable by other means. The U.S. Orphan Drug Act of 1983 and a similar proposal from the European Commission (currently under legislative approval) provide financial and practical incentives for the research and development of drugs to treat rare diseases. In addition, updated epidemiologic information from experts in the field of emerging diseases; increased disease awareness among health professionals, patients, and the general public; a list of priority vaccines; emergence of a dedicated organization with strong leadership; and the long-term pharmacoeconomic viability of orphan products will be key factors in overcoming the complexity of orphan status and the limited need for vaccine.

  3. Enhancing Malaria Vaccine Development by the Naval Medical Research Center

    National Research Council Canada - National Science Library

    Hile, David

    2001-01-01

    A priority of DoD is to develop effective vaccines for preventing malaria. Developing malaria vaccines is complicated by the complexity of the parasite and of the human host's response to the infection...

  4. Recent progress in mucosal vaccine development: potential and limitations.

    Science.gov (United States)

    Lycke, Nils

    2012-07-25

    Most pathogens access the body through the mucosal membranes. Therefore, effective vaccines that protect at these sites are much needed. However, despite early success with the live attenuated oral polio vaccine over 50 years ago, only a few new mucosal vaccines have been subsequently launched. This is partly due to problems with developing safe and effective mucosal adjuvants. In the past decade, however, the successful development of live attenuated mucosal vaccines against influenza virus and rotavirus infections has boosted interest in this field, and great expectations for new mucosal vaccines lie ahead. Here, I discuss the expanding knowledge and strategies used in the development of mucosal vaccines.

  5. AIDS vaccine for Asia Network (AVAN: expanding the regional role in developing HIV vaccines.

    Directory of Open Access Journals (Sweden)

    Stephen J Kent

    2010-09-01

    Full Text Available The HIV/AIDS pandemic continues to spread and an AIDS vaccine is urgently needed. Regional alliances and international collaborations can foster the development and evaluation of the next generation of AIDS vaccine candidates. The importance of coordinating and harmonizing efforts across regional alliances has become abundantly clear. We recently formed the AIDS Vaccine for Asia Network (AVAN to help facilitate the development of a regional AIDS vaccine strategy that accelerates research and development of an AIDS vaccine through government advocacy, improved coordination, and harmonization of research; develops clinical trial and manufacturing capacity; supports ethical and regulatory frameworks; and ensures community participation.

  6. [Current progress in the development of mucosal vaccines].

    Science.gov (United States)

    Takeyama, Natsumi; Yuki, Yoshikazu; Kiyono, Hiroshi

    2011-09-01

    Mucosal vaccination has several advantages compared with that of injection-type vaccination. Secretory IgA(SIgA) produced at mucosal surface plays a key role for inactivation of toxins and inhibition of pathogen invasion. Although oral or nasal vaccination with attenuated live microorganisms have been shown to be effective in the induction of protective immunity, these types of vaccine have the ability to infect transiently to the host. For the development of safe and effective mucosal vaccine, an obvious strategy is the preparation of inactivated subunit-type mucosal vaccine. Here we introduce our frontier technology for the development of rice-based oral vaccines, as a new generation of mucosal vaccine. Further, we also discuss recent progress in the development of other types of mucosal vaccine and adjuvant.

  7. Development of Burkholderia mallei and pseudomallei vaccines

    Directory of Open Access Journals (Sweden)

    Ediane Batista Silva

    2013-03-01

    Full Text Available B. mallei and B. pseudomallei are Gram-negative bacteria that cause glanders and melioidosis, respectively. Inhalational infection with either organism can result in severe and rapidly fatal pneumonia. Inoculation by the oral and cutaneous routes can also produce infection. chronic infection develops after recovery from acute infection with both agents, and control of infection with antibiotics requires prolonged treatment. Symptoms for both meliodosis and glanders are non-specific, making diagnosis difficult.B. pseudomallei can be located in the environment, but in the host, B. mallei and B. psedomallei are intracellular organisms. Thefection results in similar immune responses to both agents. Effective early innate immune responses are critical to controlling the early phase of the infection. Innate immune signaling molecules such as TLR, NOD, MyD88 and pro-inflammatory cytokines such as IFN- and TNF-α play key roles in regulating control of infection. Neutrophils and monocytes are critical cells in the early infection for these microorganisms. Both monocytes and macrophages are necessary for limiting dissemination of B. pseudomallei. In contrast, the role of adaptive immune responses in controlling Burkholderia infection is less well understood. However, T cell responses are critical for vaccine protection from Burkholderia infection. At present, effective vaccines for prevention of glanders or meliodosis have not been developed, although recently progress of Burkholderia vaccines has received renewed attention.This review will summarize current and past approaches to develop Burkholderia mallei and pseudomalllei vaccines, with emphasis on immune mechanisms of protection and the challenges facing the field. At present, immunization with live attenuated bacteria provides the most effective and durable immunity, and it is important therefore to understand the immune correlates of protection induced by live attenuated vaccines.

  8. Selected regulatory and scientific topics for candidate rotavirus vaccine development.

    Science.gov (United States)

    Henchal, L S; Midthun, K; Goldenthal, K L

    1996-09-01

    Various aspects of the development of rotavirus vaccine candidates are discussed. As is true with other vaccines, comprehensive testing must be done to detect the possible presence of adventitious agents in the vaccine and seed preparations. Consideration must also be given to other biologic materials that come in contact with the vaccine preparation during production to prevent the introduction of contaminants. The clinical testing of rotavirus vaccines from early safety and immunogenicity studies through final efficacy studies is also discussed. Issues surrounding coadministration of investigational rotavirus vaccines with US-licensed vaccines are ideally addressed before initiation of efficacy trials. Other subjects discussed are identification of correlates of protection, multivalent vaccines, foreign efficacy trials, safety data, and statistical considerations. Sponsors of investigational vaccines are urged to contact the Food and Drug Administration for guidance during the development process, especially before the investigational new drug application and pivotal efficacy trial stages.

  9. The Importance of Animal Models in Tuberculosis Vaccine Development

    OpenAIRE

    Acosta, Armando; Norazmi, Mohd Nor; Hernandez-Pando, Rogelio; Alvarez, Nadine; Borrero, Reinier; Infante, Juan F; Sarmiento, Maria E

    2011-01-01

    Research, development, and production of vaccines are still highly dependent on the use of animal models in the various evaluation steps. Despite this fact, there are strong interests and ongoing efforts to reduce the use of animals in vaccine development. Tuberculosis vaccine development is one important example of the complexities involved in the use of animal models for the production of new vaccines. This review summarises some of the general aspects related with the use of animals in vac...

  10. Obstacles and advances in SARS vaccine development.

    Science.gov (United States)

    Taylor, Deborah R

    2006-02-13

    The emergence of the severe acute respiratory syndrome (SARS) that resulted in a pandemic in 2003 spurred a flurry of interest in the development of vaccines to prevent and treat the potentially deadly viral infection. Researchers around the world pooled their scientific resources and shared early data in an unprecedented manner in light of the impending public health crisis. There are still large gaps in knowledge about the pathogenesis of this virus. While significant advances have been made in the development of animal models, the practicality of their use may be hampered by a lack of pathological similarity with human disease. Described here are issues related to progress in vaccine development and the obstacles that lie ahead for both researchers and regulatory agencies.

  11. Development of thermostable lyophilized inactivated polio vaccine.

    Science.gov (United States)

    Kraan, Heleen; van Herpen, Paul; Kersten, Gideon; Amorij, Jean-Pierre

    2014-10-01

    The aim of current study was to develop a dried inactivated polio vaccine (IPV) formulation with minimal loss during the drying process and improved stability when compared with the conventional liquid IPV. Extensive excipient screening was combined with the use of a Design of Experiment (DoE) approach in order to achieve optimal results with high probability. Although it was shown earlier that the lyophilization of a trivalent IPV while conserving its antigenicity is challenging, we were able to develop a formulation that showed minimal loss of potency during drying and subsequent storage at higher temperatures. This study showed the potential of a highly stable and safe lyophilized polio vaccine, which might be used in developing countries without the need of a cold-chain.

  12. Update on the Clinical Development of Candidate Malaria Vaccines

    National Research Council Canada - National Science Library

    Ballou, W. R; Arevalo-Herrera, Myriam; Carucci, Daniel; Richie, Thomas L; Corradin, Giampietro; Diggs, Carter; Druilhe, Pierre; Giersing, Birgitte K; Saul, Allan; Heppner, D. G

    2004-01-01

    ... powerful driver for stimulating clinical development of candidate vaccines for malaria. This new way forward promises to greatly increase the likelihood of bringing a safe and effective vaccine to licensure...

  13. A history of the development of Brucella vaccines.

    Science.gov (United States)

    Avila-Calderón, Eric Daniel; Lopez-Merino, Ahidé; Sriranganathan, Nammalwar; Boyle, Stephen M; Contreras-Rodríguez, Araceli

    2013-01-01

    Brucellosis is a worldwide zoonosis affecting animal and human health. In the last several decades, much research has been performed to develop safer Brucella vaccines to control the disease mainly in animals. Till now, no effective human vaccine is available. The aim of this paper is to review and discuss the importance of methodologies used to develop Brucella vaccines in pursuing this challenge.

  14. Advances in molecular biology: impact on rotavirus vaccine development.

    Science.gov (United States)

    Estes, M K

    1996-09-01

    The first candidate rotavirus vaccine was a live attenuated oral vaccine made by the classical empirical method of serial passage of virus in tissue culture cells. Current tetravalent vaccine candidates that are in the final stages of efficacy testing in the United States were made by genetic reassortment. This article briefly highlights how advances in the basic understanding of the molecular biology of rotaviruses have facilitated vaccine development. New approaches for second-generation vaccines and improvements in vaccine efficacy based on further exploitation of the tools and knowledge of rotavirus molecular biology and pathogenesis are discussed.

  15. Accelerating vaccine development for African swine fever virus ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    2018-01-12

    Jan 12, 2018 ... Expected results. By adopting this cutting-edge approach to the development of African swine fever vaccines, the overall expected result is the generation of a vaccine candidate that will undergo further testing and if successful, be produced as a new vaccine for ASF.

  16. Challenges and opportunities for meningococcal vaccination in the developing world.

    Science.gov (United States)

    Shaker, Rouba; Fayad, Danielle; Dbaibo, Ghassan

    2018-02-02

    Meningococcal disease continues to be a life threatening infection with high morbidity and mortality even in appropriately treated patients. Meningococcal vaccination plays a major role in the control of the disease; however, implementing vaccination remains problematic in the developing world. The objective of this review is to identify the challenges facing the use of meningococcal vaccines in the developing world in order to discuss the opportunities and available solutions to improve immunization in these countries. Inadequate epidemiologic information necessary to implement vaccination and financial challenges predominate. Multiple measures are needed to achieve the successful implementation of meningococcal conjugate vaccination programs that protect against circulating serogroups in developing countries including enhanced surveillance systems, financial support and aid through grants, product development partnerships that are the end result of effective collaboration and communication between different interdependent stakeholders to develop affordable vaccines, and demonstration of the cost-effectiveness of new meningococcal vaccines.

  17. [Rabies vaccines: Current status and prospects for development].

    Science.gov (United States)

    Starodubova, E S; Preobrazhenskaia, O V; Kuzmenko, Y V; Latanova, A A; Yarygina, E I; Karpov, V L

    2015-01-01

    Rabies is an infectious disease among humans and animals that remains incurable, despite its longstanding research history. The only way to prevent the disease is prompt treatment, including vaccination as an obligatory component and administration of antirabies immunoglobulin as a supplement. Since the first antirabies vaccination performed in the 19th century, a large number of different rabies vaccines have been developed. Progress in molecular biology and biotechnology enabled the development of effective and safe technologies of vaccine production. Currently, new-generation vaccines are being developed based on recombinant rabies virus strains or on the production of an individual recombinant rabies antigen-glycoprotein (G protein), either as a component of nonpathogenic viruses, or in plants, or in the form of DNA vaccines. In this review, the main modern trends in the development of rabies vaccines have been discussed.

  18. Immunoinformatics of Placental Malaria Vaccine Development

    DEFF Research Database (Denmark)

    Jessen, Leon Eyrich

    Malaria is an infectious disease caused by a protozoan parasite of the genus Plasmodium, which is transferred by female Anopheles mosquitos. WHO estimates that in 2012 there were 207 million cases of malaria, of which 627,000 were fatal. People living in malaria-endemic areas, gradually acquire...... immunity with multiple infections. Placental malaria (PM) is caused by P. falciparum sequestering in the placenta of pregnant women due to the presence of novel receptors in the placenta. An estimated 200,000 infants die a year as a result of PM. In 2004 the specific protein responsible...... and development in the field of placental malaria vaccine development....

  19. Impact of BRICS’ investment in vaccine development on the global vaccine market

    Science.gov (United States)

    Milstien, Julie; Schmitt, Sarah

    2014-01-01

    Abstract Brazil, the Russian Federation, India, China and South Africa – the countries known as BRICS – have made considerable progress in vaccine production, regulation and development over the past 20 years. In 1993, all five countries were producing vaccines but the processes used were outdated and non-standardized, there was little relevant research and there was negligible international recognition of the products. By 2014, all five countries had strong initiatives for the development of vaccine technology and had greatly improved their national regulatory capacity. South Africa was then the only BRICS country that was not completely producing vaccines. South Africa is now in the process of re-establishing its own vaccine production and passing beyond the stage of simply importing, formulating and filling vaccine bulks. Changes in the public sector’s price per dose of selected vaccines, the global market share represented by products from specific manufacturers, and the attractiveness, for multinational companies, of partnership and investment opportunities in BRICS companies have all been analysed. The results indicate that the BRICS countries have had a major impact on vaccine price and availability, with much of that impact attributable to the output of Indian vaccine manufacturers. China is expected to have a greater impact soon, given the anticipated development of Chinese vaccine manufacturers in the near future. BRICS’ accomplishments in the field of vaccine development are expected to reshape the global vaccine market and accelerate access to vaccines in the developing world. The challenge is to turn these expectations into strategic actions and practical outcomes. PMID:24940018

  20. Research progress in live attenuated Brucella vaccine development.

    Science.gov (United States)

    Wang, Zhen; Wu, Qingmin

    2013-01-01

    Brucella spp. are facultative intracellular bacteria that cause brucellosis, which is a globally occurring zoonotic disease that is characterized by abortion in domestic animals and undulant fever, arthritis, endocarditis, and meningitis in humans. There are currently no licensed vaccines against brucellosis for human use, and only a few licensed live Brucella vaccines are available for use in animals. However, the available animal vaccines may cause abortion and are associated with lower protection rates in animals and higher virulence in humans. Much research has been performed recently to develop novel Brucella vaccines for the prevention and control of animal brucellosis. This article discusses the approaches and strategies for novel live attenuated vaccine development.

  1. Review: New Vaccine Against Tuberculosis: Current Developments and Future Challenges

    Science.gov (United States)

    Liu, Jun

    2009-04-01

    Tuberculosis (TB) continues to be a global health threat. BCG was developed as an attenuated live vaccine for tuberculosis control nearly a century ago. Despite being the most widely used vaccine in human history, BCG is not an ideal vaccine and has two major limitations: its poor efficacy against adult pulmonary TB and its disconcerting safety in immunocompromised individuals. A safer and more effective TB vaccine is urgently needed. This review article discusses current strategies to develop the next generation of TB vaccines to replace BCG. While some progresses have been made in the past decade, significant challenges lie ahead.

  2. Vaxjo: A Web-Based Vaccine Adjuvant Database and Its Application for Analysis of Vaccine Adjuvants and Their Uses in Vaccine Development

    Directory of Open Access Journals (Sweden)

    Samantha Sayers

    2012-01-01

    Full Text Available Vaccine adjuvants are compounds that enhance host immune responses to co-administered antigens in vaccines. Vaxjo is a web-based central database and analysis system that curates, stores, and analyzes vaccine adjuvants and their usages in vaccine development. Basic information of a vaccine adjuvant stored in Vaxjo includes adjuvant name, components, structure, appearance, storage, preparation, function, safety, and vaccines that use this adjuvant. Reliable references are curated and cited. Bioinformatics scripts are developed and used to link vaccine adjuvants to different adjuvanted vaccines stored in the general VIOLIN vaccine database. Presently, 103 vaccine adjuvants have been curated in Vaxjo. Among these adjuvants, 98 have been used in 384 vaccines stored in VIOLIN against over 81 pathogens, cancers, or allergies. All these vaccine adjuvants are categorized and analyzed based on adjuvant types, pathogens used, and vaccine types. As a use case study of vaccine adjuvants in infectious disease vaccines, the adjuvants used in Brucella vaccines are specifically analyzed. A user-friendly web query and visualization interface is developed for interactive vaccine adjuvant search. To support data exchange, the information of vaccine adjuvants is stored in the Vaccine Ontology (VO in the Web Ontology Language (OWL format.

  3. Hepatitis A in the US Army: epidemiology and vaccine development.

    Science.gov (United States)

    Hoke, C H; Binn, L N; Egan, J E; DeFraites, R F; MacArthy, P O; Innis, B L; Eckels, K H; Dubois, D; D'Hondt, E; Sjogren, M H

    1992-01-01

    Control of hepatitis A has been an important concern for US military forces in war and peace. Immune serum globulin, although effective, is exceedingly cumbersome to use. The prevalence of antibody against hepatitis A is decreasing in young American soldiers, putting them at risk of hepatitis A during deployment. The US Army has been an active participant in development of hepatitis A vaccine. The first successful cell-culture-derived, formalin-inactivated hepatitis A vaccine was developed at the Walter Reed Army Institute of Research. This prototype vaccine was shown, in 1986, to be safe and immunogenic for humans. Since then we have evaluated the following issues related to the use of inactivated hepatitis A vaccines in military populations. Immunogenicity of vaccine derived from the CLF and HM175 strains; immunogenicity of hepatitis A vaccine given by jet injector; immunogenicity of hepatitis A vaccine when given with hepatitis B vaccine; immunogenicity when given in shortened schedules; safety and immunogenicity in Thai children; and efficacy under field conditions in the tropics. The hepatitis A vaccines which we tested are safe and highly immunogenic. Immunization by jet gun confers immunity equivalent to immunization by needle. Hepatitis A vaccine is equally potent when given with hepatitis B vaccine. Data on rapid immunization schedules and efficacy are under evaluation. We conclude that hepatitis A vaccine is a major improvement in our ability to prevent hepatitis A in soldiers.

  4. Reverse Vaccinology: Developing Vaccines in the Era of Genomics

    Science.gov (United States)

    Sette, Alessandro; Rappuoli, Rino

    2012-01-01

    The sequence of microbial genomes made all potential antigens of each pathogen available for vaccine development. This increased by orders of magnitude potential vaccine targets in bacteria, parasites, and large viruses and revealed virtually all their CD4+ and CD8+ T cell epitopes. The genomic information was first used for the development of a vaccine against serogroup B meningococcus, and it is now being used for several other bacterial vaccines. In this review, we will first summarize the impact that genome sequencing has had on vaccine development, and then we will analyze how the genomic information can help further our understanding of immunity to infection or vaccination and lead to the design of better vaccines by diving into the world of T cell immunity. PMID:21029963

  5. Vaccine Development for Zika Virus-Timelines and Strategies.

    Science.gov (United States)

    Durbin, Anna P

    2016-09-01

    Zika virus is a mosquito-borne Flavivirus that spread rapidly through South and Central America in 2015 to 2016. Microcephaly has been causally associated with Zika virus infection during pregnancy and the World Health Organization declared Zika virus as a Public Health Emergency of International Concern. To address this crisis, many groups have expressed their commitment to developing a Zika virus vaccine. Different strategies for Zika virus vaccine development are being considered including recombinant live attenuated vaccines, purified inactivated vaccines (PIVs), DNA vaccines, and viral vectored vaccines. Important to Zika virus vaccine development will be the target group chosen for vaccination and which end point(s) is chosen for efficacy determination. The first clinical trials of Zika virus vaccine candidates will begin in Q3/4 2016 but the pathway to licensure for a Zika virus vaccine is expected to take several years. Efforts are ongoing to accelerate Zika virus vaccine development and evaluation with the ultimate goal of reducing time to licensure. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  6. Development of an HIV vaccine attitudes scale to predict HIV vaccine acceptability among vulnerable populations: L.A. VOICES

    OpenAIRE

    Lee, SJ; Newman, PA; Duan, N.; Cunningham, WE

    2014-01-01

    Background: Decade-long delays in successful implementation of Hepatitis B vaccines and ongoing obstacles in HPV vaccine roll-out suggest the importance of an implementation science approach to prepare for the effective translation of future HIV vaccines from clinical trials into routine practice. The objective of this study was to test HIV vaccine attitude items to develop reliable scales and to examine their association with HIV vaccine acceptability. Methods: HIV vaccine attitude items wer...

  7. Vaccines to prevent pneumonia in children - a developing country perspective.

    Science.gov (United States)

    Oliwa, Jacquie N; Marais, Ben J

    2017-03-01

    Pneumonia accounted for 15% of the 6.3 million deaths among children younger than five years in 2013, a total of approximately 935,000 deaths worldwide. Routine vaccination against common childhood illnesses has been identified as one of the most cost-effective strategies to prevent death from pneumonia. Vaccine-preventable or potentially preventable diseases commonly linked with respiratory tract infections include Streptococcus pneumoniae, Haemophilus influenza type-b (Hib), pertussis, influenza, measles, and tuberculosis. Although here have been great strides in the development and administration of effective vaccines, the countries that carry the largest disease burdens still struggle to vaccinate their children and newer conjugated vaccines remain out of reach for many. The Global Vaccine Action Plan (GVAP) has identified priority areas for innovation in research in all aspects of immunisation development and delivery to ensure equitable access to vaccines for all. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Guiding dengue vaccine development using knowledge gained from the success of the yellow fever vaccine.

    Science.gov (United States)

    Liang, Huabin; Lee, Min; Jin, Xia

    2016-01-01

    Flaviviruses comprise approximately 70 closely related RNA viruses. These include several mosquito-borne pathogens, such as yellow fever virus (YFV), dengue virus (DENV), and Japanese encephalitis virus (JEV), which can cause significant human diseases and thus are of great medical importance. Vaccines against both YFV and JEV have been used successfully in humans for decades; however, the development of a DENV vaccine has encountered considerable obstacles. Here, we review the protective immune responses elicited by the vaccine against YFV to provide some insights into the development of a protective DENV vaccine.

  9. Recent update in HIV vaccine development

    National Research Council Canada - National Science Library

    Shin, So Youn

    2016-01-01

    .... Disappointing results from previous clinical trials of VaxGen's AIDSVAXgp120 vaccine and MRKAd5 HIV-1 Gag/Pol/Nef vaccine emphasize that understanding the correlates of immune protection in HIV...

  10. Nonclinical Development of BCG Replacement Vaccine Candidates

    OpenAIRE

    Bernd Eisele; Martin Gengenbacher; Reginald Kidd; David McCown; Sheldon Morris; Steven Derrick; David Hokey; Dominick Laddy; Rosemary Chang; Megan Fitzpatrick; Leander Grode; Kamalakannan Velmurugan; Kaufmann,Stefan H. E.; John Fulkerson; Brennan, Michael J.

    2013-01-01

    The failure of current Mycobacterium bovis bacille Calmette–Guérin (BCG) vaccines, given to neonates to protect against adult tuberculosis and the risk of using these live vaccines in HIV-infected infants, has emphasized the need for generating new, more efficacious and safer replacement vaccines. With the availability of genetic techniques for constructing recombinant BCG (rBCG) strains containing well-defined gene deletions or insertions, new vaccine candidates are under evaluation at both ...

  11. Leishmaniasis vaccine candidates for development: a global overview.

    Science.gov (United States)

    Khamesipour, Ali; Rafati, Sima; Davoudi, Noushin; Maboudi, Fereidoun; Modabber, Farrokh

    2006-03-01

    A vaccine against different forms of leishmaniasis should be feasible considering the wealth of information on genetics and biology of the parasite, clinical and experimental immunology of leishmaniasis, and the availability of vaccines that can protect experimental animals against challenge with different Leishmania species. However, there is no vaccine against any form of leishmaniasis for general human use. One major factor is the lack of a conceived market for human leishmaniasis vaccines. Hence pharmaceutical industries involved in vaccine development are not interested in investing millions of dollars and a decade that is required for developing a new vaccine. Besides, leishmaniasis is a local/regional problem and not a global one. According to the estimates of the World Health Organization, 90 per cent of visceral leishmaniasis occurs in five countries (Bangladesh, Brazil, India, Nepal and Sudan). Those in need are amongst the poorest people in these countries. It should therefore be the objectives of these countries to develop a vaccine. Fortunately, both Brazil and India have designated the control of visceral leishmaniasis as a top priority for their respective Ministries of Health. The purpose of this review is to present only the vaccines in use and those in development for use in dogs or humans. This is not an exhaustive review of vaccine discovery or the principles of clinical immunology underlying vaccine development.

  12. HIV-1 Polymorphism: a Challenge for Vaccine Development - A Review

    Directory of Open Access Journals (Sweden)

    Morgado MG

    2002-01-01

    Full Text Available The perspective for the development of anti-HIV/AIDS vaccines became a target sought by several research groups and pharmaceutical companies. However, the complex virus biology in addition to a striking genetic variability and the limited understanding of the immunological correlates of protection have made this an enormous scientific challenge not overcome so far. In this review we presented an updating of HIV-1 subtypes and recombinant viruses circulating in South American countries, focusing mainly on Brazil, as one of the challenges for HIV vaccine development. Moreover, we discussed the importance of stimulating developing countries to participate in the process of vaccine evaluation, not only testing vaccines according to already defined protocols, but also working together with them, in order to take into consideration their local information on virus diversity and host genetic background relevant for the vaccine development and testing, as well as including local virus based reagents to evaluate the immunogenicity of the candidate vaccines.

  13. Progress in Developing Virus-like Particle Influenza Vaccines

    Science.gov (United States)

    Quan, Fu-Shi; Lee, Young-Tae; Kim, Ki-Hye; Kim, Min-Chul; Kang, Sang-Moo

    2016-01-01

    Summary Recombinant vaccines based on virus-like particles (VLPs) or nanoparticles have been successful in their safety and efficacy in preclinical and clinical studies. The technology of expressing enveloped VLP vaccines has combined with molecular engineering of proteins in membrane-anchor and immunogenic forms mimicking the native conformation of surface proteins on the enveloped viruses. This review summarizes recent developments in influenza VLP vaccines against seasonal, pandemic, and avian influenza viruses from the perspective of use in humans. The immunogenicity and efficacies of influenza VLP vaccine in the homologous and cross-protection were reviewed. Discussions include limitations of current influenza vaccination strategies and future directions to confer broadly cross protective new influenza vaccines as well as vaccination. PMID:27058302

  14. Current Trends in West Nile Virus Vaccine Development

    Science.gov (United States)

    Amanna, Ian J.; Slifka, Mark K.

    2014-01-01

    West Nile virus (WNV) is a mosquito-borne flavivirus that has become endemic in the United States. From 1999-2012, there have been 37,088 reported cases of WNV and 1,549 deaths, resulting in a 4.2% case-fatality rate. Despite development of effective WNV vaccines for horses, there is no vaccine to prevent human WNV infection. Several vaccines have been tested in preclinical studies and to date there have been 8 clinical trials, with promising results in terms of safety and induction of antiviral immunity. Although mass vaccination is unlikely to be cost-effective, implementation of a targeted vaccine program may be feasible if a safe and effective vaccine can be brought to market. Further evaluation of new and advanced vaccine candidates is strongly encouraged. PMID:24689659

  15. A History of the Development of Brucella Vaccines

    OpenAIRE

    Eric Daniel Avila-Calderón; Ahidé Lopez-Merino; Nammalwar Sriranganathan; Boyle, Stephen M; Araceli Contreras-Rodríguez

    2013-01-01

    Brucellosis is a worldwide zoonosis affecting animal and human health. In the last several decades, much research has been performed to develop safer Brucella vaccines to control the disease mainly in animals. Till now, no effective human vaccine is available. The aim of this paper is to review and discuss the importance of methodologies used to develop Brucella vaccines in pursuing this challenge. CONACYT CB-2011-01, 169259 SIP-IPN 20110891, 20134610 ICYTDF-IPN (Project of Investiga...

  16. A History of the Development of Brucella Vaccines

    Directory of Open Access Journals (Sweden)

    Eric Daniel Avila-Calderón

    2013-01-01

    Full Text Available Brucellosis is a worldwide zoonosis affecting animal and human health. In the last several decades, much research has been performed to develop safer Brucella vaccines to control the disease mainly in animals. Till now, no effective human vaccine is available. The aim of this paper is to review and discuss the importance of methodologies used to develop Brucella vaccines in pursuing this challenge.

  17. Prospects and Challenges in the Development of a Norovirus Vaccine.

    Science.gov (United States)

    Cortes-Penfield, Nicolas W; Ramani, Sasirekha; Estes, Mary K; Atmar, Robert L

    2017-08-01

    Norovirus is the leading cause of acute epidemic gastroenteritis among children under the age of 5 years and adults in the United States and in adults worldwide, accounting for an estimated 20% of episodes of acute gastroenteritis across all ages. No effective vaccine is presently available. This article provides an overview of the current state of norovirus vaccine development, emphasizing barriers and challenges in the development of an effective vaccine, correlates of protection used to assess vaccine efficacy, and the results of clinical trials of the major candidate vaccines. We performed an unstructured literature review of published articles listed in PubMed in the field of norovirus vaccine development, with an emphasis on studies in humans. Two candidate vaccines have reached clinical trials, and a number of other candidates are in the preclinical stages of development. Multivalent vaccination may be effective in inducing broadly neutralizing antibodies protective against challenge with novel and heterologous norovirus strains. Most identified correlates of protection have not been validated in large-scale challenge studies, nor have the degrees to which these correlates covary been assessed. Immune correlates of protection against norovirus infection need to be further developed to facilitate additional studies of the tolerability and efficacy of candidate norovirus vaccines in humans. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

  18. Vaccines against enteric infections for the developing world

    Science.gov (United States)

    Czerkinsky, Cecil; Holmgren, Jan

    2015-01-01

    Since the first licensure of the Sabin oral polio vaccine more than 50 years ago, only eight enteric vaccines have been licensed for four disease indications, and all are given orally. While mucosal vaccines offer programmatically attractive tools for facilitating vaccine deployment, their development remains hampered by several factors: —limited knowledge regarding the properties of the gut immune system during early life;—lack of mucosal adjuvants, limiting mucosal vaccine development to live-attenuated or killed whole virus and bacterial vaccines;—lack of correlates/surrogates of mucosal immune protection; and—limited knowledge of the factors contributing to oral vaccine underperformance in children from developing countries.There are now reasons to believe that the development of safe and effective mucosal adjuvants and of programmatically sound intervention strategies could enhance the efficacy of current and next-generation enteric vaccines, especially in lesser developed countries which are often co-endemic for enteric infections and malnutrition. These vaccines must be safe and affordable for the world's poorest, confer long-term protection and herd immunity, and must be able to contain epidemics. PMID:25964464

  19. An intensive 5-year-long influenza vaccination campaign is effective among doctors but not nurses.

    Science.gov (United States)

    Friedl, A; Aegerter, C; Saner, E; Meier, D; Beer, J H

    2012-02-01

    To double the vaccination rates of hospital employees from 20 to 40% by specific interventions over a 5-year period (2003-2007). The secondary endpoint was to compare the effects of the avian influenza in 2005 (intervention period) and the H1N1 influenza pandemic in 2009 (follow-up period, 2008-2009) on vaccination rates. Free vaccination and its intensive propagation from 2003-2007 in a 400-bed teaching hospital with 1,687 hospital employees. Annual vaccination rates were obtained from 2003 through 2009. Yearly vaccination rates for the intervention period from 2003-2007 and the observational follow-up period of 2008-2009. The overall rate for seasonal influenza vaccination changed non-significantly during the intervention period from 20% in 2003 to 27% in 2007. At the end of the follow-up period in 2009, the vaccination rate was 26%, which was not significantly higher compared with that in 2003. Physicians interestingly increased from 34% in 2003 to 62% in 2007 and to 66% in 2009 (p vaccination. The difference between nurses and doctors in 2007 is highly significant (p vaccine uptake was 33% (p vaccine in 2003). Overall, the vaccination rates did not increase over the 7-year study period. Interventions were successful for physicians but not for nurses. The vaccine uptake was significantly higher during the threat of avian influenza and the influenza A/H1N1v pandemic.

  20. Advancements in the development of subunit influenza vaccines

    Science.gov (United States)

    Zhang, Naru; Zheng, Bo-Jian; Lu, Lu; Zhou, Yusen; Jiang, Shibo; Du, Lanying

    2014-01-01

    The ongoing threat of influenza epidemics and pandemics has emphasized the importance of developing safe and effective vaccines against infections from divergent influenza viruses. In this review, we first introduce the structure and life cycle of influenza A viruses, describing major influenza A virus-caused pandemics. We then compare different types of influenza vaccines and discuss current advancements in the development of subunit influenza vaccines, particularly those based on nucleoprotein (NP), extracellular domain of matrix protein 2 (M2e) and hemagglutinin (HA) proteins. We also illustrate potential strategies for improving the efficacy of subunit influenza vaccines. PMID:25529753

  1. Vaccines against Toxoplasma gondii: new developments and perspectives.

    Science.gov (United States)

    Zhang, Nian-Zhang; Chen, Jia; Wang, Meng; Petersen, Eskild; Zhu, Xing-Quan

    2013-11-01

    Toxoplasmosis caused by the protozoan Toxoplasma gondii is a major public health problem, infecting one-third of the world human beings, and leads to abortion in domestic animals. A vaccine strategy would be an ideal tool for improving disease control. Many efforts have been made to develop vaccines against T. gondii to reduce oocyst shedding in cats and tissue cyst formation in mammals over the last 20 years, but only a live-attenuated vaccine based on the S48 strain has been licensed for veterinary use. Here, the authors review the recent development of T. gondii vaccines in cats, food-producing animals and mice, and present its future perspectives. However, a single or only a few antigen candidates revealed by various experimental studies are limited by only eliciting partial protective immunity against T. gondii. Future studies of T. gondii vaccines should include as many CTL epitopes as the live attenuated vaccines.

  2. [Development of transcutaneous vaccination system for infectious disease countermeasure].

    Science.gov (United States)

    Matsuo, Kazuhiko

    2012-01-01

    The recent vigorous transnational migration of people and materials reflecting the development of transportation facilities, changes in social structure, and war disasters has increased the global spread of emerging and re-emerging infections. Once, as the 2009 pandemic influenza A (H1N1) virus, person-to-person transmission was achieved, the spread of pandemic cannot be contained in reality. Thus enhancement of the crisis-management structure against pandemic is critically important to maintain national function. On the basis of this social background, the development of vaccination, which is the only fundamental prophylaxis, is in attention, and earliest possible establishment of system that supply mass-vaccines in a short time is required. Even if, however, rapid manufacture of vaccine antigen is actualized, there are several problems that vaccine is not easily spread across the developing country and mass vaccination is not performed immediately at the time of the crisis, because conventional vaccination is performed mainly by injection. Our research group developed transcutaneous vaccine devices; a hydrogel patch and a dissolving microneedle array which delivered antigens to antigen-presenting cells in the epidermal layer. Our transcutaneous vaccination system receives a high evaluation as novel, easy-to-use, and less-invasive vaccination method against infections from home and abroad. In this review, we introduce the research progress resulted from our basic, preclinical, and clinical study for practical use.

  3. Strategic priorities for respiratory syncytial virus (RSV) vaccine development

    Science.gov (United States)

    Anderson, L.J.; Dormitzer, P.R.; Nokes, D.J.; Rappuoli, R.; Roca, A.; Graham, B.S.

    2013-01-01

    Although RSV has been a high priority for vaccine development, efforts to develop a safe and effective vaccine have yet to lead to a licensed product. Clinical and epidemiologic features of RSV disease suggest there are at least 4 distinct target populations for vaccines, the RSV naïve young infant, the RSV naïve child ≥6 months of age, pregnant women (to provide passive protection to newborns), and the elderly. These target populations raise different safety and efficacy concerns and may require different vaccination strategies. The highest priority target population is the RSV naïve child. The occurrence of serious adverse events associated with the first vaccine candidate for young children, formalin inactivated RSV (FI-RSV), has focused vaccine development for the young RSV naïve child on live virus vaccines. Enhanced disease is not a concern for persons previously primed by a live virus infection. A variety of live-attenuated viruses have been developed with none yet achieving licensure. New live-attenuated RSV vaccines are being developed and evaluated that maybe sufficiently safe and efficacious to move to licensure. A variety of subunit vaccines are being developed and evaluated primarily for adults in whom enhanced disease is not a concern. An attenuated parainfluenza virus 3 vector expressing the RSV F protein was evaluated in RSV naïve children. Most of these candidate vaccines have used the RSV F protein in various vaccine platforms including virus-like particles, nanoparticles, formulated with adjuvants, and expressed by DNA or virus vectors. The other surface glycoprotein, the G protein, has also been used in candidate vaccines. We now have tools to make and evaluate a wide range of promising vaccines. Costly clinical trials in the target population are needed to evaluate and select candidate vaccines for advancement to efficacy trials. Better data on RSV-associated mortality in developing countries, better estimates of the risk of long term

  4. Current and Novel Approaches to Vaccine Development Against Tuberculosis

    OpenAIRE

    Mark eCayabyab; Lilia eMacovei; Antonio eCampos-Neto

    2012-01-01

    Antibiotics and vaccines are the two most successful medical countermeasures that humans have created against a number of pathogens. However a select few e.g., Mycobacterium tuberculosis, the causative agent of tuberculosis (TB) have evaded eradication by vaccines and therapeutic approaches. TB is a global public health problem that kills 1.4 million people per year. The past decade has seen significant progress in developing new vaccine candidates, but the most fundamental questions in under...

  5. Antimicrobial Carbohydrate Vaccines: Development of Burkholderia pseudomallei immunogens

    OpenAIRE

    Donaldson, Matthew

    2013-01-01

    The potential bio-terror threat posed by Burkholderia pseudomallei highlights the need for an effective vaccine. Immunisation and challenge experiments in mice have demonstrated that the capsular polysaccharide (CPS-1) of B. pseudomallei, which is composed of β-1,3-linked 6-deoxy-D-manno-heptopyranose residues, is a promising candidate for vaccine development. This thesis set out to explore routes to potential vaccine candidates for Burkholderia pseudomallei infection based on ...

  6. New developments and concepts related to biomarker application to vaccines

    Science.gov (United States)

    Ahmed, S. Sohail; Black, Steve; Ulmer, Jeffrey

    2012-01-01

    Summary This minireview will provide a perspective on new developments and concepts related to biomarker applications for vaccines. In the context of preventive vaccines, biomarkers have the potential to predict adverse events in select subjects due to differences in genetic make‐up/underlying medical conditions or to predict effectiveness (good versus poor response). When expanding them to therapeutic vaccines, their utility in identification of patients most likely to respond favourably (or avoid potentially negative effects of treatment) becomes self‐explanatory. Despite the progress made so far on dissection of various pathways of biological significance in humans, there is still plenty to unravel about the mysteries related to the quantitative and qualitative aspects of the human host response. This review will provide a focused overview of new concepts and developments in the field of vaccine biomarkers including (i) vaccine‐dependent signatures predicting subject response and safety, (ii) predicting therapeutic vaccine efficacy in chronic diseases, (iii) exploring the genetic make‐up of the host that may modulate subject‐specific adverse events or affect the quality of immune responses, and (iv) the topic of volunteer stratification as a result of biomarker screening (e.g. for therapeutic vaccines but also potentially for preventive vaccines) or as a reflection of an effort to compare select groups (e.g. vaccinated subjects versus patients recovering from infection) to enable the discovery of clinically relevant biomarkers for preventive vaccines. PMID:21895991

  7. Killed oral cholera vaccines: history, development and implementation challenges.

    Science.gov (United States)

    Lopez, Anna Lena; Gonzales, Maria Liza Antoinette; Aldaba, Josephine G; Nair, G Balakrish

    2014-09-01

    Cholera is still a major global health problem, affecting mainly people living in unsanitary conditions and who are at risk for outbreaks of cholera. During the past decade, outbreaks are increasingly reported from more countries. From the early killed oral cholera vaccine, rapid improvements in vaccine development occurred as a result of a better understanding of the epidemiology of the disease, pathogenesis of cholera infection and immunity. The newer-generation oral killed cholera vaccines have been shown to be safe and effective in field trials conducted in cholera endemic areas. Likewise, they have been shown to be protective when used during outbreak settings. Aside from providing direct protection to vaccinated individuals, recent studies have demonstrated that these killed oral vaccines also confer indirect protection through herd immunity. Although new-generation oral cholera vaccines should not be considered in isolation from other preventive approaches in countries where they are most needed, especially improved water quality and sanitation, these vaccines serve as immediately available public health tools for preventing further morbidity and mortality from cholera. However, despite its availability for more than two decades, use of these vaccines has not been optimized. Although there are limitations of the currently available oral cholera vaccines, recent data show that the vaccines are safe, feasible to use even in difficult circumstances and able to provide protection in various settings. Clear identification of the areas and target population groups who will benefit from the use of the cholera vaccines will be required and strategies to facilitate accessibility and usage of these vaccines in these areas and population groups will need to be developed.

  8. WHO policy development processes for a new vaccine: case study of malaria vaccines.

    Science.gov (United States)

    Milstien, Julie; Cárdenas, Vicky; Cheyne, James; Brooks, Alan

    2010-06-24

    Recommendations from the World Health Organization (WHO) are crucial to inform developing country decisions to use, or not, a new intervention. This article analysed the WHO policy development process to predict its course for a malaria vaccine. The decision-making processes for one malaria intervention and four vaccines were classified through (1) consultations with staff and expert advisors to WHO's Global Malaria Programme (GMP) and Immunization, Vaccines and Biologicals Department (IVB); (2) analysis of the procedures and recommendations of the major policy-making bodies of these groups; (3) interviews with staff of partnerships working toward new vaccine availability; and (4) review and analyses of evidence informing key policy decisions. WHO policy formulation related to use of intermittent preventive treatment in infancy (IPTi) and the following vaccine interventions: Haemophilus influenzae type b conjugate vaccine (Hib), pneumococcal conjugate vaccine (PCV), rotavirus vaccine (RV), and human papillomavirus vaccine (HPV), five interventions which had relatively recently been through systematic WHO policy development processes as currently constituted, was analysed. Required information was categorized in three areas defined by a recent WHO publication on development of guidelines: safety and efficacy in relevant populations, implications for costs and population health, and localization of data to specific epidemiological situations. Data needs for a malaria vaccine include safety; the demonstration of efficacy in a range of epidemiological settings in the context of other malaria prevention interventions; and information on potential rebound in which disease increases subsequent to the intervention. In addition, a malaria vaccine would require attention to additional factors, such as costs and cost-effectiveness, supply and demand, impact of use on other interventions, and distribution issues. Although policy issues may be more complex for future vaccines

  9. WHO policy development processes for a new vaccine: case study of malaria vaccines

    Directory of Open Access Journals (Sweden)

    Cheyne James

    2010-06-01

    Full Text Available Abstract Background Recommendations from the World Health Organization (WHO are crucial to inform developing country decisions to use, or not, a new intervention. This article analysed the WHO policy development process to predict its course for a malaria vaccine. Methods The decision-making processes for one malaria intervention and four vaccines were classified through (1 consultations with staff and expert advisors to WHO's Global Malaria Programme (GMP and Immunization, Vaccines and Biologicals Department (IVB; (2 analysis of the procedures and recommendations of the major policy-making bodies of these groups; (3 interviews with staff of partnerships working toward new vaccine availability; and (4 review and analyses of evidence informing key policy decisions. Case description WHO policy formulation related to use of intermittent preventive treatment in infancy (IPTi and the following vaccine interventions: Haemophilus influenzae type b conjugate vaccine (Hib, pneumococcal conjugate vaccine (PCV, rotavirus vaccine (RV, and human papillomavirus vaccine (HPV, five interventions which had relatively recently been through systematic WHO policy development processes as currently constituted, was analysed. Required information was categorized in three areas defined by a recent WHO publication on development of guidelines: safety and efficacy in relevant populations, implications for costs and population health, and localization of data to specific epidemiological situations. Discussion and evaluation Data needs for a malaria vaccine include safety; the demonstration of efficacy in a range of epidemiological settings in the context of other malaria prevention interventions; and information on potential rebound in which disease increases subsequent to the intervention. In addition, a malaria vaccine would require attention to additional factors, such as costs and cost-effectiveness, supply and demand, impact of use on other interventions, and

  10. Scaling up development, production of CBPP vaccine for cattle in ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Development of a Subunit Vaccine for Contagious Bovine Pleuropneumonia in Africa (CIFSRF Phase 2). This project will allow researchers from Canada and Kenya to field trial a vaccine for contagious bovine pleuropneumonia. This endemic livestock disease affects the livelihoods of more than 24 million cattle producers ...

  11. Development of new generation influenza vaccines: Recipes for success?

    NARCIS (Netherlands)

    Pronker, E.S.; Claassen, E.; Osterhaus, A.D.M.E.

    2012-01-01

    As infectious diseases cause approximately 25% of the annual global mortality, vaccines are found to be a time proven and promising response to infectious disease need. However, like for pharmaceutical small molecules, vaccine development is lengthy, risky and resource demanding. Faced with an

  12. Successes and failures in human tuberculosis vaccine development.

    Science.gov (United States)

    Zenteno-Cuevas, Roberto

    2017-12-01

    Tuberculosis (TB) is an infectious disease caused mainly by Mycobacterium tuberculosis. In 2016, the WHO estimated 10.5 million new cases and 1.8 million deaths, making this disease the leading cause of death by an infectious agent. The current and projected TB situation necessitates the development of new vaccines with improved attributes compared to the traditional BCG method. Areas covered: In this review, the authors describe the most promising candidate vaccines against TB and discuss additional key elements in vaccine development, such as animal models, new adjuvants and immunization routes and new strategies for the identification of candidate vaccines. Expert opinion: At present, around 13 candidate vaccines for TB are in the clinical phase of evaluation; however, there is still no substitute for the BCG vaccine. One major impediment to developing an effective vaccine is our lack of understanding of several of the mechanisms associated with infection and the immune response against TB. However, the recent implementation of an entirely new set of technological advances will facilitate the proposal of new candidates. Finally, development of a new vaccine will require a major coordination of effort in order to achieve its effective administration to the people most in need of it.

  13. Efforts Towards The Development Of Recombinant Vaccines Against

    African Journals Online (AJOL)

    ABSTRACT. Hemorrhagic septicemia is caused by gram-negative bacterium of Pasteurella multocida (P. multocida) strains. Most of the current vaccines against P. multocida have shortcomings. Presently, there is increasing efforts towards construction of recombinant clone for vaccine development against P. multocida.

  14. Efforts towards the development of recombinant Vaccines against ...

    African Journals Online (AJOL)

    Hemorrhagic septicemia is caused by gram-negative bacterium of Pasteurella multocida (P. multocida) strains. Most of the current vaccines against P. multocida have shortcomings. Presently, there is increasing efforts towards construction of recombinant clone for vaccine development against P. multocida. In this review an ...

  15. The path of malaria vaccine development: challenges and perspectives.

    Science.gov (United States)

    Arama, C; Troye-Blomberg, M

    2014-05-01

    Malaria is a life-threatening disease caused by parasites of the Plasmodium genus. In many parts of the world, the parasites have developed resistance to a number of antimalarial agents. Key interventions to control malaria include prompt and effective treatment with artemisinin-based combination therapies, use of insecticidal nets by individuals at risk and active research into malaria vaccines. Protection against malaria through vaccination was demonstrated more than 30 years ago when individuals were vaccinated via repeated bites by Plasmodium falciparum-infected and irradiated but still metabolically active mosquitoes. However, vaccination with high doses of irradiated sporozoites injected into humans has long been considered impractical. Yet, following recent success using whole-organism vaccines, the approach has received renewed interest; it was recently reported that repeated injections of irradiated sporozoites increased protection in 80 vaccinated individuals. Other approaches include subunit malaria vaccines, such as the current leading candidate RTS,S (consisting of fusion between a portion of the P. falciparum-derived circumsporozoite protein and the hepatitis B surface antigen), which has been demonstrated to induce reasonably good protection. Although results have been encouraging, the level of protection is generally considered to be too low to achieve eradication of malaria. There is great interest in developing new and better formulations and stable delivery systems to improve immunogenicity. In this review, we will discuss recent strategies to develop efficient malaria vaccines. © 2014 The Association for the Publication of the Journal of Internal Medicine.

  16. Edible vaccine: a new platform for the development of malaria vaccine.

    Science.gov (United States)

    Kumar, Choudhary Sudheer; Deepesh, Gupta; Mahavir, Yadav; Archana, Tiwari

    2012-01-01

    The plasmodium vivax is the most prevalent malaria parasite. The world essentially needs a malaria vaccine to alleviate the human suffering associated with the parasitic disease that kills more than one million people annually. The use of plants for the expression of the proteins of disease-causing vehicle in transgenic plants has been increasingly used in the development of experimental vaccines, largely oriented to the improvement of edible vaccines. Currently, through modern biotechnology, there has been a revival in obtaining a new edible vaccine against the malaria parasite from plant sources. Through genetic alteration, it is now recognized that plants are potentially a new source of recombinant proteins including vaccines, antibodies, blood substitutes, and other therapeutic entities. Plant-derived antibodies and other proteins are mostly valuable since they are free of mammalian viral vectors and human pathogens. Although significant progress has been achieved in the research for edible vaccine in Plasmodium falciparum, limited progress has been made in the Plasmodium vivax component that might be eligible for edible vaccine development. We describe the overall strategy recommended by plants, which include high biomass production and low cost of cultivation, relatively fast "gene to protein" time, low capital and operating costs, outstanding scalability, eukaryotic posttranslational modifications, and a relatively high protein yield.

  17. Large animal models for vaccine development and testing.

    Science.gov (United States)

    Gerdts, Volker; Wilson, Heather L; Meurens, Francois; van Drunen Littel-van den Hurk, Sylvia; Wilson, Don; Walker, Stewart; Wheler, Colette; Townsend, Hugh; Potter, Andrew A

    2015-01-01

    The development of human vaccines continues to rely on the use of animals for research. Regulatory authorities require novel vaccine candidates to undergo preclinical assessment in animal models before being permitted to enter the clinical phase in human subjects. Substantial progress has been made in recent years in reducing and replacing the number of animals used for preclinical vaccine research through the use of bioinformatics and computational biology to design new vaccine candidates. However, the ultimate goal of a new vaccine is to instruct the immune system to elicit an effective immune response against the pathogen of interest, and no alternatives to live animal use currently exist for evaluation of this response. Studies identifying the mechanisms of immune protection; determining the optimal route and formulation of vaccines; establishing the duration and onset of immunity, as well as the safety and efficacy of new vaccines, must be performed in a living system. Importantly, no single animal model provides all the information required for advancing a new vaccine through the preclinical stage, and research over the last two decades has highlighted that large animals more accurately predict vaccine outcome in humans than do other models. Here we review the advantages and disadvantages of large animal models for human vaccine development and demonstrate that much of the success in bringing a new vaccine to market depends on choosing the most appropriate animal model for preclinical testing. © The Author 2015. Published by Oxford University Press on behalf of the Institute for Laboratory Animal Research. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  18. Zika Virus: Immunity and Vaccine Development

    National Research Council Canada - National Science Library

    Pierson, Theodore C; Graham, Barney S

    2016-01-01

    The emergence of Zika virus in the Americas and Caribbean created an urgent need for vaccines to reduce transmission and prevent disease, particularly the devastating neurodevelopmental defects that occur in utero...

  19. Development of DNA vaccines for fish

    DEFF Research Database (Denmark)

    Heppell, Joël; Lorenzen, Niels; Armstrong, Neil K.

    1998-01-01

    Disease control is one of the major concerns in the aquaculture industry. However, there are no vaccines available for the prevention of many piscine infectious diseases, especially those of viral and parasitic origin. DNA-based vaccination could circumvent several problems associated...... no permanent tissue damage. To further investigate the ability of DNA-based vaccines to induce protective immunity in fish, viral haemorrhagic septicaemia virus G and N genes were cloned individually into an expression plasmid. Both G and N proteins produced in transfected fish cells appeared identical...... protein, killing the transfected host cells and ablating further expression of G protein and luciferase. Finally, young rainbow trout injected with the G construct, alone or together with the N construct, were strongly protected against challenge with live virus. These results suggest that DNA vaccines...

  20. Preclinical and clinical development of DNA vaccines for prostate cancer.

    Science.gov (United States)

    Colluru, V T; Johnson, Laura E; Olson, Brian M; McNeel, Douglas G

    2016-04-01

    Prostate cancer is the most commonly diagnosed cancer in the United States. It is also the second leading cause of cancer-related death in men, making it one of the largest public health concerns today. Prostate cancer is an ideal disease for immunotherapies because of the generally slow progression, the dispensability of the target organ in the patient population, and the availability of several tissue-specific antigens. As such, several therapeutic vaccines have entered clinical trials, with one autologous cellular vaccine (sipuleucel-T) recently gaining Food and Drug Administration approval after demonstrating overall survival benefit in randomized phase III clinical trials. DNA-based vaccines are safe, economical, alternative "off-the-shelf" approaches that have undergone extensive evaluation in preclinical models. In fact, the first vaccine approved in the United States for the treatment of cancer was a DNA vaccine for canine melanoma. Several prostate cancer-specific DNA vaccines have been developed in the last decade and have shown promising results in early phase clinical trials. This review summarizes anticancer human DNA vaccine trials, with a focus on those conducted for prostate cancer. We conclude with an outline of special considerations important for the development and successful translation of DNA vaccines from the laboratory to the clinic. © 2013 Published by Elsevier Inc.

  1. Status of vaccine research and development of vaccines for herpes simplex virus.

    Science.gov (United States)

    Johnston, Christine; Gottlieb, Sami L; Wald, Anna

    2016-06-03

    Herpes simplex virus type-1 (HSV-1) and -2 (HSV-2) are highly prevalent global pathogens which commonly cause recurrent oral and genital ulcerations. Less common but more serious complications include meningitis, encephalitis, neonatal infection, and keratitis. HSV-2 infection is a significant driver of the HIV epidemic, increasing the risk of HIV acquisition 3 fold. As current control strategies for genital HSV-2 infection, including antiviral therapy and condom use, are only partially effective, vaccines will be required to reduce infection. Both preventive and therapeutic vaccines for HSV-2 are being pursued and are in various stages of development. We will provide an overview of efforts to develop HSV-2 vaccines, including a discussion of the clinical need for an HSV vaccine, and status of research and development with an emphasis on recent insights from trials of vaccine candidates in clinical testing. In addition, we will touch upon aspects of HSV vaccine development relevant to low and middle income countries. Copyright © 2016 World Health Organization. Published by Elsevier Ltd.. All rights reserved.

  2. Status of vaccine research and development for Shigella.

    Science.gov (United States)

    Mani, Sachin; Wierzba, Thomas; Walker, Richard I

    2016-06-03

    Shigella are gram-negative bacteria that cause severe diarrhea and dysentery. In 2013, Shigella infections caused an estimated 34,400 deaths in children less than five years old and, in 2010, an estimated 40,000 deaths in persons older than five years globally. New disease burden estimates from newly deployed molecular diagnostic assays with increased sensitivity suggest that Shigella-associated morbidity may be much greater than previous disease estimates from culture-based methods. Primary prevention of this disease should be based on universal provision of potable water and sanitation methods and improved personal and food hygiene. However, an efficacious and low-cost vaccine would complement and accelerate disease reduction while waiting for universal access to water, sanitation, and hygiene improvements. This review article provides a landscape of Shigella vaccine development efforts. No vaccine is yet available, but human and animal challenge-rechallenge trials with virulent Shigella as well as observational studies in Shigella-endemic areas have shown that the incidence of disease decreases following Shigella infection, pointing to biological feasibility of a vaccine. Immunity to Shigella appears to be strain-specific, so a vaccine that covers the most commonly detected strains (i.e., S. flexneri 2a, 3a, 6, and S. sonnei) or a vaccine using cross-species conserved antigens would likely be most effective. Vaccine development and testing may be accelerated by use of animal models, such as the guinea pig keratoconjunctivitis or murine pneumonia models. Because there is no correlate of protection, however, human studies will be necessary to evaluate vaccine efficacy prior to deployment. A diversity of Shigella vaccine constructs are under development, including live attenuated, formalin-killed whole-cell, glycoconjugate, subunit, and novel antigen vaccines (e.g., Type III secretion system and outer membrane proteins). Copyright © 2016 World Health Organization

  3. Use of nonhuman primate models to develop mucosal AIDS vaccines.

    Science.gov (United States)

    Genescà, Meritxell; Miller, Christopher J

    2010-02-01

    The HIV vaccines tested in the halted Step efficacy trial and the modestly successful phase 3 RV144 trial were designed to elicit strong systemic immune responses; therefore, strategies to direct immune responses into mucosal sites should be tested in an effort to improve AIDS vaccine efficacy. However, as increased CD4(+) T-cell activation and recruitment to mucosal sites have the potential to enhance HIV transmission, mucosal immune responses to HIV vaccines should primarily consist of effector CD8(+) T cells and plasma cells. Controlling the level of mucosal T-cell activation may be a critical factor in developing an effective mucosal AIDS vaccine. Immunization routes and adjuvants that can boost antiviral immunity in mucosal surfaces offer a reasonable opportunity to improve AIDS vaccine efficacy. Nonhuman primate models offer the best system for preclinical evaluation of these approaches.

  4. Vaccine procurement and self-sufficiency in developing countries.

    Science.gov (United States)

    Woodle, D

    2000-06-01

    This paper discusses the movement toward self-sufficiency in vaccine supply in developing countries (and countries in transition to new economic and political systems) and explains special supply concerns about vaccine as a product class. It traces some history of donor support and programmes aimed at self-financing, then continues with a discussion about self-sufficiency in terms of institutional capacity building. A number of deficiencies commonly found in vaccine procurement and supply in low- and middle-income countries are characterized, and institutional strengthening with procurement technical assistance is described. The paper also provides information about a vaccine procurement manual being developed by the United States Agency for International Development (USAID) and the World Health Organization (WHO) for use in this environment. Two brief case studies are included to illustrate the spectrum of existing capabilities and different approaches to technical assistance aimed at developing or improving vaccine procurement capability. In conclusion, the paper discusses the special nature of vaccine and issues surrounding potential integration and decentralization of vaccine supply systems as part of health sector reform.

  5. Challenges in the research and development of new human vaccines

    Directory of Open Access Journals (Sweden)

    T. Barbosa

    2013-02-01

    Full Text Available The field of vaccinology was born from the observations by the fathers of vaccination, Edward Jenner and Louis Pasteur, that a permanent, positive change in the way our bodies respond to life-threatening infectious diseases can be obtained by specific challenge with the inactivated infectious agent performed in a controlled manner, avoiding the development of clinical disease upon exposure to the virulent pathogen. Many of the vaccines still in use today were developed on an empirical basis, essentially following the paradigm established by Pasteur, “isolate, inactivate, and inject” the disease-causing microorganism, and are capable of eliciting uniform, long-term immune memory responses that constitute the key to their proven efficacy. However, vaccines for pathogens considered as priority targets of public health concern are still lacking. The literature tends to focus more often on vaccine research problems associated with specific pathogens, but it is increasingly clear that there are common bottlenecks in vaccine research, which need to be solved in order to advance the development of the field as a whole. As part of a group of articles, the objective of the present report is to pinpoint these bottlenecks, exploring the literature for common problems and solutions in vaccine research applied to different situations. Our goal is to stimulate brainstorming among specialists of different fields related to vaccine research and development. Here, we briefly summarize the topics we intend to deal with in this discussion.

  6. Advances in the development of vaccines for dengue fever

    Directory of Open Access Journals (Sweden)

    Simmons M

    2012-05-01

    Full Text Available Monika Simmons1, Nimfa Teneza-Mora1, Robert Putnak21Viral and Rickettsial Diseases Department, Naval Medical Research Center, 2Division of Viral Diseases, Walter Reed Army Institute of Research, Silver Spring, MD, USAAbstract: Dengue fever is caused by the mosquito-borne dengue virus (DENV serotypes 1–4, and is the most common arboviral infection of humans in subtropical and tropical regions of the world. There are currently no prophylaxis or treatment options in the form of vaccines or antivirals, leaving vector control the only method of prevention. A particular challenge with DENV is that a successful vaccine has to be effective against all four serotypes without predisposing for antibody-mediated enhanced disease. In this review, we discuss the current lead vaccine candidates in clinical trials, as well as some second-generation vaccine candidates undergoing preclinical evaluation. In addition, we discuss DENV epidemiology, clinical disease and strategies used for Flavivirus antivirals in the past, the development of new DENV therapeutics, and their potential usefulness for prophylaxis and treatment.Keywords: tetravalent dengue vaccine, live attenuated vaccine, purified inactivated vaccine, DNA vaccine, antibody-dependent enhancement, antivirals

  7. The impact of globalization on vaccine development and availability.

    Science.gov (United States)

    Milstien, Julie B; Kaddar, Miloud; Kieny, Marie Paule

    2006-01-01

    Globalization is likely to affect many aspects of public health, one of which is vaccine-preventable communicable diseases. Important forces include increased funding initiatives supporting immunization at the global level; regulatory harmonization; widespread intellectual property rights provisions through the World Trade Organization agreements; the emergence of developing-country manufacturers as major players in vaccine supply; and the appearance of new communicable disease threats, including those potentially linked to bioterrorism. All of these forces can affect, either positively and negatively, the development and availability of vaccines. Harnessing these will be a challenge for policymakers and immunization stakeholders.

  8. Possibilities and challenges for developing a successful vaccine for leishmaniasis.

    Science.gov (United States)

    Srivastava, Saumya; Shankar, Prem; Mishra, Jyotsna; Singh, Sarman

    2016-05-12

    Leishmaniasis is a vector-borne disease caused by different species of protozoan parasites of the genus Leishmania. It is a major health problem yet neglected tropical diseases, with approximately 350 million people worldwide at risk and more than 1.5 million infections occurring each year. Leishmaniasis has different clinical manifestations, including visceral (VL or kala-azar), cutaneous (CL), mucocutaneous (MCL), diffuse cutaneous (DCL) and post kala-azar dermal leishmaniasis (PKDL). Currently, the only mean to treat and control leishmaniasis is by rational medications and vector control. However, the number of available drugs is limited and even these are either exorbitantly priced, have toxic side effects or prove ineffective due to the emergence of resistant strains. On the other hand, the vector control methods are not so efficient. Therefore, there is an urgent need for developing a safe, effective, and affordable vaccine for the prevention of leishmaniasis. Although in recent years a large body of researchers has concentrated their efforts on this issue, yet only three vaccine candidates have gone for clinical trial, until date. These are: (i) killed vaccine in Brazil for human immunotherapy; (ii) live attenuated vaccine for humans in Uzbekistan; and (iii) second-generation vaccine for dog prophylaxis in Brazil. Nevertheless, there are at least half a dozen vaccine candidates in the pipeline. One can expect that, in the near future, the understanding of the whole genome of Leishmania spp. will expand the vaccine discovery and strategies that may provide novel vaccines. The present review focuses on the development and the status of various vaccines and potential vaccine candidates against leishmaniasis.

  9. Options for improving effectiveness of rotavirus vaccines in developing countries

    Science.gov (United States)

    Cowley, Daniel; Bogdanovic-Sakran, Nada; Hutton, Melanie L.; Lyras, Dena; Kirkwood, Carl D.; Buttery, Jim P.

    2017-01-01

    ABSTRACT Rotavirus gastroenteritis is a leading global cause of mortality and morbidity in young children due to diarrhea and dehydration. Over 85% of deaths occur in developing countries. In industrialised countries, 2 live oral rotavirus vaccines licensed in 2006 quickly demonstrated high effectiveness, dramatically reducing severe rotavirus gastroenteritis admissions in many settings by more than 90%. In contrast, the same vaccines reduced severe rotavirus gastroenteritis by only 30–60% in developing countries, but have been proven life-saving. Bridging this “efficacy gap” offers the possibility to save many more lives of children under the age of 5. The reduced efficacy of rotavirus vaccines in developing settings may be related to differences in transmission dynamics, as well as host luminal, mucosal and immune factors. This review will examine strategies currently under study to target the issue of reduced efficacy and effectiveness of oral rotavirus vaccines in developing settings. PMID:27835052

  10. Nanotechnology Laboratory Collaborates with Army to Develop Botulism Vaccine | FNLCR

    Science.gov (United States)

    The Nanotechnology Characterization Laboratory (NCL) is collaborating with the Army to develop a candidate vaccine against botulism. Under a collaboration agreement between the National Cancer Institute and the U.S. Army Medical Research Institute of

  11. Dengue, zika, chikungunya and the development of vaccines

    Directory of Open Access Journals (Sweden)

    Isabel N. Kantor

    2018-01-01

    Full Text Available Dengue (DENV, zika (ZIKV and chikungunya (CHIKV, three arbovirosis transmitted by Aedes mosquitoes, have spread in recent decades in humid tropical and subtropical zones. Dengue is epidemic in subtropical areas of Argentina. DENV infection confers lasting immunity against the infecting serotype but increases the risk of serious disease upon reinfection by any of the other three. The recombinant tetravalent vaccine Dengvaxia® prevents severe dengue and hospitalization in seropositive subjects. In 2017, Dengvaxia was approved in Argentina, for ages 9 to 45, but is not included in the national vaccination calendar. Two other vaccines are in Phase III evaluation: one developed by NIAID / Instituto Butantan and the other by Takeda. ZIKV, a virus associated with microcephaly in newborns in Brazil, circulates since 2016 in Argentina. There is still not effective treatment nor vaccine with proven activity against ZIKV. There has been no active circulation of CHIKV in Argentina in 2017. Outbreaks of CHIKV fever have a complication: the development of chronic post-disease rheumatism. There are not approved vaccines for humans nor effective antiviral therapies. The seriousness of these virosis has contributed to a rapid progress in the knowledge of the infection processes and the immune response. For now, Aedes aegypti and A. albopictus vectors continue to expand, suggesting that the vaccine will be the most effective means of controlling these viruses. Here we summarize information about these arbovirosis in Argentina and Brazil and describe advances in the development and evaluation of vaccines.

  12. Live attenuated hepatitis A vaccines developed in China.

    Science.gov (United States)

    Xu, Zhi-Yi; Wang, Xuan-Yi

    2014-01-01

    Two live, attenuated hepatitis A vaccines, H 2 and LA-1 virus strains, were developed through serial passages of the viruses in cell cultures at 32 °C and 35 °C respectively. Both vaccines were safe and immunogenic, providing protection against clinical hepatitis A in 95% of the vaccinees, with a single dose by subcutaneous injection. The vaccine recipients were not protected from asymptomatic, subclinical hepatitis A virus (HAV) infection, which induced a similar antibody response as for unvaccinated subjects. A second dose caused anamnestic response and can be used for boosting. Oral immunization of human with H 2 vaccine or of marmoset with LA-1 vaccine failed, and no evidence was found for person-to-person transmission of the H 2 strain or for marmoset-to-marmoset transmission of LA-1 strain, by close contact. H 2 strain was genetically stable when passaged in marmosets, humans or cell cultures at 37 °C; 3 consecutive passages of the virus in marmosets did not cause virulence mutation. The live vaccines offer the benefits of low cost, single dose injection, long- term protection, and increased duration of immunity through subclinical infection. Improved sanitation and administration of 150 million doses of the live vaccines to children had led to a 90% reduction in the annual national incidence rate of hepatitis A in China during the 16-year period, from 1991 to 2006. Hepatitis A immunization with both live and inactivated HA vaccines was implemented in the national routine childhood immunization program in 2008 and around 92% of the 16 million annual births received the affordable live, attenuated vaccines at 18 months of age. Near elimination of the disease was achieved in China for 14 years following introduction of the H 2 live vaccine into the Expanded Immunization Program (EPI) in 1992.

  13. Live attenuated hepatitis A vaccines developed in China

    Science.gov (United States)

    Xu, Zhi-Yi; Wang, Xuan-Yi

    2014-01-01

    Two live, attenuated hepatitis A vaccines, H2 and LA-1 virus strains, were developed through serial passages of the viruses in cell cultures at 32 °C and 35 °C respectively. Both vaccines were safe and immunogenic, providing protection against clinical hepatitis A in 95% of the vaccinees, with a single dose by subcutaneous injection. The vaccine recipients were not protected from asymptomatic, subclinical hepatitis A virus (HAV) infection, which induced a similar antibody response as for unvaccinated subjects. A second dose caused anamnestic response and can be used for boosting. Oral immunization of human with H2 vaccine or of marmoset with LA-1 vaccine failed, and no evidence was found for person-to-person transmission of H2 strain or for marmoset-to-marmoset transmission of LA-1 strain by close contact. H2 strain was genetically stable when passaged in marmosets, humans or cell cultures at 37 °C; 3 consecutive passages of the virus in marmosets did not cause virulence mutation. The live vaccines offer the benefits of low cost, single dose injection, long- term protection, and increased duration of immunity through subclinical infection. Improved sanitation and administration of 150 million doses of the live vaccines to children had led to a 90% reduction in the annual national incidence rate of hepatitis A in China during the 16-year period, from 1991 to 2006. Hepatitis A (HA) immunization with both live and inactivated HA vaccines was implemented in the national routine childhood immunization program in 2008 and around 92% of the 16 million annual births received the affordable live, attenuated vaccines at 18 months of age. Near elimination of the disease was achieved in a county of China for 14 years following introduction of the H2 live vaccine into the Expanded Immunization Program (EPI) in 1992. PMID:24280971

  14. Status of research and development of vaccines for Streptococcus pyogenes.

    Science.gov (United States)

    Steer, Andrew C; Carapetis, Jonathan R; Dale, James B; Fraser, John D; Good, Michael F; Guilherme, Luiza; Moreland, Nicole J; Mulholland, E Kim; Schodel, Florian; Smeesters, Pierre R

    2016-06-03

    Streptococcus pyogenes is an important global pathogen, causing considerable morbidity and mortality, especially in low and middle income countries where rheumatic heart disease and invasive infections are common. There is a number of promising vaccine candidates, most notably those based on the M protein, the key virulence factor for the bacterium. Vaccines against Streptococcus pyogenes are considered as impeded vaccines because of a number of crucial barriers to development. Considerable effort is needed by key players to bring current vaccine candidates through phase III clinical trials and there is a clear need to develop a roadmap for future development of current and new candidates. Copyright © 2016 World Health Organization. Published by Elsevier Ltd.. All rights reserved.

  15. Development and application of avian influenza vaccines in China.

    Science.gov (United States)

    Chen, Hualan; Bu, Zhigao

    2009-01-01

    Following the first detection of the highly pathogenic H5N1 avian influenza virus in sick geese in Guangdong Province in China in 1996, scientists began to develop vaccines in preparation for an avian influenza pandemic. An inactivated H5N2 vaccine was produced from a low pathogenic virus, A/turkey/England/N-28/73, and was used for buffer zone vaccination during H5N1 outbreaks in 2004 in China. We also generated a low pathogenic H5N1 reassortant virus (Re-1) that derives its HA and NA genes from the GS/GD/96 virus and six internal genes from the high-growth A/Puerto Rico/8/34 (PR8) virus using plasmid-based reverse genetics. The inactivated vaccine derived from the Re-1 strain could induce more than ten months of protective immunity in chickens after one-dose inoculation; most importantly, this vaccine is immunogenic for geese and ducks. We recently developed a Newcastle virus-vectored live vaccine that exhibits great promise for use in the field to prevent highly pathogenic avian influenza and Newcastle disease in chickens. Over 30 billion doses of these vaccines have been used in China and other countries, including Vietnam, Mongolia, and Egypt, and have played an important role in H5N1 avian influenza control in these countries.

  16. Ensuring the optimal safety of licensed vaccines: a perspective of the vaccine research, development, and manufacturing companies.

    Science.gov (United States)

    Kanesa-thasan, Niranjan; Shaw, Alan; Stoddard, Jeffrey J; Vernon, Thomas M

    2011-05-01

    Vaccine safety is increasingly a focus for the general public, health care providers, and vaccine manufacturers, because the efficacy of licensed vaccines is accepted as a given. Commitment to ensuring safety of all vaccines, including childhood vaccines, is addressed by the federal government, academia, and industry. Safety activities conducted by the vaccine research, development, and manufacturing companies occur at all stages of product development, from selection and formulation of candidate vaccines through postlicensure studies and surveillance of adverse-event reports. The contributions of multiple interacting functional groups are required to execute these tasks through the life cycle of a product. We describe here the safeguards used by vaccine manufacturers, including specific examples drawn from recent experience, and highlight some of the current challenges. Vaccine-risk communication becomes a critical area for partnership of vaccine companies with government, professional associations, and nonprofit advocacy groups to provide information on both benefits and risks of vaccines. The crucial role of the vaccine companies in ensuring the optimal vaccine-safety profile, often overlooked, will continue to grow with this dynamic arena.

  17. The moral case for the routine vaccination of children in developed and developing countries.

    Science.gov (United States)

    Dawson, Angus

    2011-06-01

    In developed countries some parents have decided not to provide routine vaccinations for their children, while in many developing countries there are inadequate rates of vaccination for various reasons. The consequences for children, and members of the community in which they live, can be significant and even tragic. Although some parents may worry that vaccines will harm their child, there is a broader moral case for vaccination that parents and policy makers should consider. This case has four components: benefits and harms, best interests, community benefits, and justice. This moral case should be central to deliberations about vaccination by parents and policy makers.

  18. IgE reactivity to vaccine components in dogs that developed immediate-type allergic reactions after vaccination.

    Science.gov (United States)

    Ohmori, Keitaro; Masuda, Kenichi; Maeda, Sadatoshi; Kaburagi, Yukiko; Kurata, Keigo; Ohno, Koichi; Deboer, Douglas J; Tsujimoto, Hajime; Sakaguchi, Masahiro

    2005-04-08

    Allergic reactions after vaccination are considered as an important practical problem in dogs; however, their immunological mechanism has not been well understood. The present study was designed to investigate the relationship between IgE reactivity to the vaccines and immediate-type allergic reactions after vaccination in dogs. Sera from 10 dogs that developed immediate-type allergic reactions such as circulatory collapse, cyanosis, dyspnea, facial edema, and vomiting within 1h after vaccination with non-rabies monovalent or combined vaccines and sera from 50 dogs that did not develop allergic reactions after vaccination were collected. Serum IgE reactivity to the injected vaccines was measured by fluorometric ELISA using a mouse monoclonal anti-dog IgE antibody. Then, IgE reactivity to fetal calf serum (FCS) and stabilizer proteins (gelatin, casein, and peptone) included in the vaccines was measured in sera that had high levels of IgE to the vaccines. Levels of serum specific IgE to the vaccines in dogs with immediate-type allergic reactions (59-4173 fluorescence units [FU], mean +/- S.D.: 992.5 +/- 1181.9 FU) were significantly higher than those in control dogs (38-192 FU, 92.4 +/- 43.3 FU) (P reactions and had high levels of serum specific IgE to the vaccines, seven had specific IgE directed to FCS. The IgE reactivity to the vaccines in sera from these dogs was almost completely inhibited by FCS. The other one dog had serum IgE directed to gelatin and casein included in the vaccine as stabilizers. The results obtained in this study suggest that immediate-type allergic reactions after vaccination in dogs were induced by type I hypersensitivity mediated by IgE directed to vaccine components. In addition, FCS, gelatin, and casein included in vaccines could be the causative allergens that induced immediate-type allergic reactions after vaccination in dogs.

  19. Risk in Vaccine Research and Development Quantified

    NARCIS (Netherlands)

    E.S. Pronker (Esther); T.C. Weenen (Tamar); H.R. Commandeur (Harry); H.J.H.M. Claassen (Eric); A.D.M.E. Osterhaus (Albert)

    2013-01-01

    textabstractTo date, vaccination is the most cost-effective strategy to combat infectious diseases. Recently, a productivity gap affects the pharmaceutical industry. The productivity gap describes the situation whereby the invested resources within an industry do not match the expected product

  20. Risk in vaccine research and development quantified

    NARCIS (Netherlands)

    Pronker, E.S.; Commandeur, H.R.; Weenen, van H.; Claassen, H.J.H.M.; Osterhaus, A.D.

    2013-01-01

    To date, vaccination is the most cost-effective strategy to combat infectious diseases. Recently, a productivity gap affects the pharmaceutical industry. The productivity gap describes the situation whereby the invested resources within an industry do not match the expected product turn-over. While

  1. Clinical development of placental malaria vaccines and immunoassays harmonization

    DEFF Research Database (Denmark)

    Chêne, Arnaud; Houard, Sophie; Nielsen, Morten A

    2016-01-01

    Placental malaria caused by Plasmodium falciparum infection constitutes a major health problem manifesting as severe disease and anaemia in the mother, impaired fetal development, low birth weight or spontaneous abortion. Prevention of placental malaria currently relies on two key strategies...... that are losing efficacy due to spread of resistance: long-lasting insecticide-treated nets and intermittent preventive treatment during pregnancy. A placental malaria vaccine would be an attractive, cost-effective complement to the existing control tools. Two placental malaria vaccine candidates are currently...... in Phase Ia/b clinical trials. During two workshops hosted by the European Vaccine Initiative, one in Paris in April 2014 and the other in Brussels in November 2014, the main actors in placental malaria vaccine research discussed the harmonization of clinical development plans and of the immunoassays...

  2. Access to vaccine technologies in developing countries: Brazil and India.

    Science.gov (United States)

    Milstien, Julie B; Gaulé, Patrick; Kaddar, Miloud

    2007-11-01

    This study, conducted by visits, interviews, and literature search, analyzes how vaccine manufacturers in Brazil and India access technologies for innovative vaccines: through collaborations with academia and research institutions, technology transfer agreements with multinational corporations, public sector, or developing country organizations, or by importation and finishing of bulk products. Each has advantages and disadvantages in terms of speed, market, and ability to independently produce the product. Most manufacturers visited are very concerned about avoiding patent infringement, which might result in undeveloped or delayed products because of a lack of mastery of the patent landscape. Disregarding the patent picture could also threaten the market of a potential product. Although it is too soon to assess the effects of TRIPS on vaccine technology access in Brazil and India, a good understanding of intellectual property management will be useful. A case study on development of a new combination vaccine illustrates these findings.

  3. [Advances in the development of vaccines for bovine neosporosis].

    Science.gov (United States)

    Hecker, Yanina P; Venturini, María C; Campero, Carlos M; Odeón, Anselmo C; Moore, Dadín P

    2012-01-01

    Neosporosis, a disease caused by the obligate intracellular protozoan Neospora caninum, produces abortions in cattle. The severe economic losses in cattle industry justify the need to develop control measures for preventing bovine abortion. Apicomplexan parasitic resistance is associated with T helper 1 immune response mediated by CD4 cytotoxic T lymphocytes, the production of interferon-gamma, interleukin-12, tumor necrosis factor and immunoglobulin G2. The reduction of vertical transmission in subsequent pregnancies and the low levels of abortion repetition suggests the existence of protective immune mechanisms. Inoculation with live tachyzoites before mating protects against infection and abortion. Antecedents of the development of live vaccines against other protozoa stimulate research to develop a live vaccine against N. caninum. On the other hand, an inactivated vaccine with low efficacy against neosporosis is useful in the prevention of abortion in farms with epizootic disease. A neosporosis vaccine should avoid abortion, transplacental transmission and infection persistence. In the present work, advances in vaccine development including lysate of tachyzoites, live parasites, recombinant antigens and vaccine vectors are reviewed.

  4. Platform for Plasmodium vivax vaccine discovery and development.

    Science.gov (United States)

    Valencia, Sócrates Herrera; Rodríguez, Diana Carolina; Acero, Diana Lucía; Ocampo, Vanessa; Arévalo-Herrera, Myriam

    2011-08-01

    Plasmodium vivax is the most prevalent malaria parasite on the American continent. It generates a global burden of 80-100 million cases annually and represents a tremendous public health problem, particularly in the American and Asian continents. A malaria vaccine would be considered the most cost-effective measure against this vector-borne disease and it would contribute to a reduction in malaria cases and to eventual eradication. Although significant progress has been achieved in the search for Plasmodium falciparum antigens that could be used in a vaccine, limited progress has been made in the search for P. vivax components that might be eligible for vaccine development. This is primarily due to the lack of in vitro cultures to serve as an antigen source and to inadequate funding. While the most advanced P. falciparum vaccine candidate is currently being tested in Phase III trials in Africa, the most advanced P. vivax candidates have only advanced to Phase I trials. Herein, we describe the overall strategy and progress in P. vivax vaccine research, from antigen discovery to preclinical and clinical development and we discuss the regional potential of Latin America to develop a comprehensive platform for vaccine development.

  5. Challenges and future in vaccines, drug development, and immunomodulatory therapy.

    Science.gov (United States)

    Kling, Heather M; Nau, Gerard J; Ross, Ted M; Evans, Thomas G; Chakraborty, Krishnendu; Empey, Kerry M; Flynn, JoAnne L

    2014-08-01

    Pulmonary diseases and infections are among the top contributors to human morbidity and mortality worldwide, and despite the successful history of vaccines and antimicrobial therapeutics, infectious disease still presents a significant threat to human health. Effective vaccines are frequently unavailable in developing countries, and successful vaccines have yet to be developed for major global maladies, such as tuberculosis. Furthermore, antibiotic resistance poses a growing threat to human health. The "Challenges and Future in Vaccines, Drug Development, and Immunomodulatory Therapy" session of the 2013 Pittsburgh International Lung Conference highlighted several recent and current studies related to treatment and prevention of antibiotic-resistant bacterial infections, highly pathogenic influenza, respiratory syncytial virus, and tuberculosis. Research presented here focused on novel antimicrobial therapies, new vaccines that are either in development or currently in clinical trials, and the potential for immunomodulatory therapies. These studies are making important contributions to the areas of microbiology, virology, and immunology related to pulmonary diseases and infections and are paving the way for improvements in the efficacy of vaccines and antimicrobials.

  6. Considerations for sustainable influenza vaccine production in developing countries.

    Science.gov (United States)

    Nannei, Claudia; Chadwick, Christopher; Fatima, Hiba; Goldin, Shoshanna; Grubo, Myriam; Ganim, Alexandra

    2016-10-26

    Through its Global Action Plan for Influenza Vaccines (GAP), the World Health Organization (WHO) in collaboration with the United States Department of Health and Human Services has produced a checklist to support policy-makers and influenza vaccine manufacturers in identifying key technological, political, financial, and logistical issues affecting the sustainability of influenza vaccine production. This checklist highlights actions in five key areas that are beneficial for establishing successful local vaccine manufacturing. These five areas comprise: (1) the policy environment and health-care systems; (2) surveillance systems and influenza evidence; (3) product development and manufacturing; (4) product approval and regulation; and (5) communication to support influenza vaccination. Incorporating the checklist into national vaccine production programmes has identified the policy gaps and next steps for countries involved in GAP's Technology Transfer Initiative. Lessons learnt from country experiences provide context and insight that complement the checklist's goal of simplifying the complexities of influenza prevention, preparedness, and vaccine manufacturing. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  7. Development of an HIV vaccine attitudes scale to predict HIV vaccine acceptability among vulnerable populations: L.A. VOICES.

    Science.gov (United States)

    Lee, Sung-Jae; Newman, Peter A; Duan, Naihua; Cunningham, William E

    2014-09-03

    Decade-long delays in successful implementation of Hepatitis B vaccines and ongoing obstacles in HPV vaccine roll-out suggest the importance of an implementation science approach to prepare for the effective translation of future HIV vaccines from clinical trials into routine practice. The objective of this study was to test HIV vaccine attitude items to develop reliable scales and to examine their association with HIV vaccine acceptability. HIV vaccine attitude items were assessed as part of the L.A. VOICES survey, a large-scale study conducted among underserved residents of Los Angeles, to identify factors that may influence HIV vaccine acceptability. Participants (n=1225) were randomly selected from public STD clinics, needle exchange sites and Latino community clinics using three-stage, venue-based time space sampling. Exploratory factor analysis across 20 items revealed four distinct factors - mistrust, HIV vaccine social concerns, risk compensation, and altruistic vaccination - with acceptable reliability coefficients for each subscale (Cronbach's α range 0.61-0.84). We found no significant differences in reliability by gender or by vaccine acceptability. Risk compensation (odds ratio (OR)=1.49; 95% CI=[1.18, 1.89]; p=0.001) and altruistic vaccination (OR=1.40; 95% CI=[1.14, 1.71]; p=0.001) were significantly and positively associated with HIV vaccine acceptability. We identified four HIV vaccine attitude scales with sound internal reliability parameters. In the aftermath of the first candidate vaccine to demonstrate efficacy against HIV infection, these scales may be helpful in bridging expectable research-to-practice gaps in future HIV vaccine dissemination among populations at risk. As HIV vaccine trials progress in the United States and globally, these measures also may be useful as a tool to assess and facilitate effective responses to community concerns about HIV vaccine trials and to target interventions to support recruitment and mitigate risk

  8. Ebola hemorrhagic Fever and the current state of vaccine development.

    Science.gov (United States)

    Hong, Joo Eun; Hong, Kee-Jong; Choi, Woo Young; Lee, Won-Ja; Choi, Yeon Hwa; Jeong, Chung-Hyeon; Cho, Kwang-Il

    2014-12-01

    Current Ebola virus outbreak in West Africa already reached the total number of 1,323 including 729 deaths by July 31st. the fatality is around 55% in the southeastern area of Guinea, Sierra Leone, Liberia, and Nigeria. The number of patients with Ebola Hemorrhagic Fever (EHF) was continuously increasing even though the any effective therapeutics or vaccines has not been developed yet. The Ebola virus in Guinea showed 98% homology with Zaire Ebola Virus. Study of the pathogenesis of Ebola virus infection and assess of the various candidates of vaccine have been tried for a long time, especially in United States and some European countries. Even though the attenuated live vaccine and DNA vaccine containing Ebola viral genes were tested and showed efficacy in chimpanzees, those candidates still need clinical tests requiring much longer time than the preclinical development to be approved for the practical treatment. It can be expected to eradicate Ebola virus by a safe and efficient vaccine development similar to the case of smallpox virus which was extinguished from the world by the variola vaccine.

  9. Novel vaccine development strategies for inducing mucosal immunity

    Science.gov (United States)

    Fujkuyama, Yoshiko; Tokuhara, Daisuke; Kataoka, Kosuke; Gilbert, Rebekah S; McGhee, Jerry R; Yuki, Yoshikazu; Kiyono, Hiroshi; Fujihashi, Kohtaro

    2012-01-01

    To develop protective immune responses against mucosal pathogens, the delivery route and adjuvants for vaccination are important. The host, however, strives to maintain mucosal homeostasis by responding to mucosal antigens with tolerance, instead of immune activation. Thus, induction of mucosal immunity through vaccination is a rather difficult task, and potent mucosal adjuvants, vectors or other special delivery systems are often used, especially in the elderly. By taking advantage of the common mucosal immune system, the targeting of mucosal dendritic cells and microfold epithelial cells may facilitate the induction of effective mucosal immunity. Thus, novel routes of immunization and antigen delivery systems also show great potential for the development of effective and safe mucosal vaccines against various pathogens. The purpose of this review is to introduce several recent approaches to induce mucosal immunity to vaccines, with an emphasis on mucosal tissue targeting, new immunization routes and delivery systems. Defining the mechanisms of mucosal vaccines is as important as their efficacy and safety, and in this article, examples of recent approaches, which will likely accelerate progress in mucosal vaccine development, are discussed. PMID:22380827

  10. Dengue human infection models to advance dengue vaccine development.

    Science.gov (United States)

    Larsen, Christian P; Whitehead, Stephen S; Durbin, Anna P

    2015-12-10

    Dengue viruses (DENV) currently infect approximately 400 million people each year causing millions to seek care and overwhelming the health care infrastructure in endemic areas. Vaccines to prevent dengue and therapeutics to treat dengue are not currently available. The efficacy of the most advanced candidate vaccine against symptomatic dengue in general and DENV-2 in particular was much lower than expected, despite the ability of the vaccine to induce neutralizing antibody against all four DENV serotypes. Because seroconversion to the DENV serotypes following vaccination was thought to be indicative of induced protection, these results have made it more difficult to assess which candidate vaccines should or should not be evaluated in large studies in endemic areas. A dengue human infection model (DHIM) could be extremely valuable to down-select candidate vaccines or therapeutics prior to engaging in efficacy trials in endemic areas. Two DHIM have been developed to assess the efficacy of live attenuated tetravalent (LATV) dengue vaccines. The first model, developed by the Laboratory of Infectious Diseases at the U. S. National Institutes of Health, utilizes a modified DENV-2 strain DEN2Δ30. This virus was derived from the DENV-2 Tonga/74 that caused only very mild clinical infection during the outbreak from which it was recovered. DEN2Δ30 induced viremia in 100%, rash in 80%, and neutropenia in 27% of the 30 subjects to whom it was given. The Walter Reed Army Institute of Research (WRAIR) is developing a DHIM the goal of which is to identify DENV that cause symptomatic dengue fever. WRAIR has evaluated seven viruses and has identified two that meet dengue fever criteria. Both of these models may be very useful in the evaluation and down-selection of candidate dengue vaccines and therapeutics. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  11. Design of clinical trials for therapeutic cancer vaccines development.

    Science.gov (United States)

    Mackiewicz, Jacek; Mackiewicz, Andrzej

    2009-12-25

    Advances in molecular and cellular biology as well as biotechnology led to definition of a group of drugs referred to as medicinal products of advanced technologies. It includes gene therapy products, somatic cell therapeutics and tissue engineering. Therapeutic cancer vaccines including whole cell tumor cells vaccines or gene modified whole cells belong to somatic therapeutics and/or gene therapy products category. The drug development is a multistep complex process. It comprises of two phases: preclinical and clinical. Guidelines on preclinical testing of cell based immunotherapy medicinal products have been defined by regulatory agencies and are available. However, clinical testing of therapeutic cancer vaccines is still under debate. It presents a serious problem since recently clinical efficacy of the number of cancer vaccines has been demonstrated that focused a lot of public attention. In general clinical testing in the current form is very expensive, time consuming and poorly designed what may lead to overlooking of products clinically beneficial for patients. Accordingly regulatory authorities and researches including Cancer Vaccine Clinical Trial Working Group proposed three regulatory solutions to facilitate clinical development of cancer vaccines: cost-recovery program, conditional marketing authorization, and a new development paradigm. Paradigm includes a model in which cancer vaccines are investigated in two types of clinical trials: proof-of-principle and efficacy. The proof-of-principle trial objectives are: safety; dose selection and schedule of vaccination; and demonstration of proof-of-principle. Efficacy trials are randomized clinical trials with objectives of demonstrating clinical benefit either directly or through a surrogate. The clinical end points are still under debate.

  12. Brucella abortus RB51: enhancing vaccine efficacy and developing multivalent vaccines.

    Science.gov (United States)

    Vemulapalli, Ramesh; He, Yongqun; Sriranganathan, Nammalwar; Boyle, Stephen M; Schurig, Gerhardt G

    2002-12-20

    Brucella abortus vaccine strain RB51 is an attenuated, stable rough mutant that is being used in many countries to control bovine brucellosis. Our earlier study demonstrated that the protective efficacy of strain RB51 can be significantly enhanced by overexpressing Cu-Zn superoxide dismutase (SOD), a homologous protective antigen. We have also previously demonstrated that strain RB51 can be engineered to express heterologous proteins and mice vaccinated with such recombinant RB51 strains develop a strong Th1 type of immune response to the foreign proteins. The present study is aimed at combining these two characteristics to generate new recombinant RB51 vaccines with enhanced abilities to protect against brucellosis and simultaneously able to protect against infections by Mycobacterium spp. We constructed two recombinant RB51 strains, RB51SOD/85A which overexpresses SOD with simultaneous expression of the 85A, a protective protein of Mycobacterium spp., and RB51ESAT which expresses ESAT-6, another protective protein of M. bovis, as a fusion protein with the signal sequence and few additional amino terminal amino acids of SOD. Mice vaccinated with these recombinant strains developed specific immune responses to the mycobacterial proteins and significantly enhanced protection against Brucella challenge compared to the mice vaccinated with strain RB51 alone. Copyright 2002 Elsevier Science B.V.

  13. Applying proteomics to tick vaccine development: where are we?

    Science.gov (United States)

    Villar, Margarita; Marina, Anabel; de la Fuente, José

    2017-03-01

    Ticks are second to mosquitoes as a vector of human diseases and are the first vector of animal diseases with a great impact on livestock farming. Tick vaccines represent a sustainable and effective alternative to chemical acaricides for the control of tick infestations and transmitted pathogens. The application of proteomics to tick vaccine development is a fairly recent area, which has resulted in the characterization of some tick-host-pathogen interactions and the identification of candidate protective antigens. Areas covered: In this article, we review the application and possibilities of various proteomic approaches for the discovery of tick and pathogen derived protective antigens, and the design of effective vaccines for the control of tick infestations and pathogen infection and transmission. Expert commentary: In the near future, the application of reverse proteomics, immunoproteomics, structural proteomics, and interactomics among other proteomics approaches will likely contribute to improve vaccine design to control multiple tick species with the ultimate goal of controlling tick-borne diseases.

  14. The search for animal models for Lassa fever vaccine development.

    Science.gov (United States)

    Lukashevich, Igor S

    2013-01-01

    Lassa virus (LASV) is the most prevalent arenavirus in West Africa and is responsible for several hundred thousand infections and thousands of deaths annually. The sizeable disease burden, numerous imported cases of Lassa fever (LF) and the possibility that LASV can be used as an agent of biological warfare make a strong case for vaccine development. Currently there is no licensed LF vaccine and research and devlopment is hampered by the high cost of nonhuman primate animal models and by biocontainment requirements (BSL-4). In addition, a successful LF vaccine has to induce a strong cell-mediated cross-protective immunity against different LASV lineages. All of these challenges will be addressed in this review in the context of available and novel animal models recently described for evaluation of LF vaccine candidates.

  15. [Prophylaxis of pertussis: development and use of acellular pertussis vaccine].

    Science.gov (United States)

    Chuprinina, R P; Alekseeva, I A; Ozeretskovskiĭ, N A

    2006-01-01

    Modern data substantiating the expediency of the use of acellular pertussis vaccine were analyzed. Serious postvaccinal complications caused by the action of the corpuscular pertussis component of adsorbed DPT vaccine served as the basis for the development of acellular pertussis vaccine (APV). During the period of 1990-1996 as many as 8 international field trials of the effectiveness of APV were carried out. The results of these trials and studies were evaluated in accordance with the unified programs and criteria. The vaccines under test differed by the composition of Bordetella pertussis purified antigens they contained, the methods of their purification and the detoxification of pertussis toxin. All tested APV, with the exception SKB-2, possessed pronounced prophylactic activity.

  16. Development of high-yield influenza A virus vaccine viruses.

    Science.gov (United States)

    Ping, Jihui; Lopes, Tiago J S; Nidom, Chairul A; Ghedin, Elodie; Macken, Catherine A; Fitch, Adam; Imai, Masaki; Maher, Eileen A; Neumann, Gabriele; Kawaoka, Yoshihiro

    2015-09-02

    Vaccination is one of the most cost-effective ways to prevent infection. Influenza vaccines propagated in cultured cells are approved for use in humans, but their yields are often suboptimal. Here, we screened A/Puerto Rico/8/34 (PR8) virus mutant libraries to develop vaccine backbones (defined here as the six viral RNA segments not encoding haemagglutinin and neuraminidase) that support high yield in cell culture. We also tested mutations in the coding and regulatory regions of the virus, and chimeric haemagglutinin and neuraminidase genes. A combination of high-yield mutations from these screens led to a PR8 backbone that improved the titres of H1N1, H3N2, H5N1 and H7N9 vaccine viruses in African green monkey kidney and Madin-Darby canine kidney cells. This PR8 backbone also improves titres in embryonated chicken eggs, a common propagation system for influenza viruses. This PR8 vaccine backbone thus represents an advance in seasonal and pandemic influenza vaccine development.

  17. Current and novel approaches to vaccine development against tuberculosis

    Science.gov (United States)

    Cayabyab, Mark J.; Macovei, Lilia; Campos-Neto, Antonio

    2012-01-01

    Antibiotics and vaccines are the two most successful medical countermeasures that humans have created against a number of pathogens. However a select few e.g., Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB) have evaded eradication by vaccines and therapeutic approaches. TB is a global public health problem that kills 1.4 million people per year. The past decade has seen significant progress in developing new vaccine candidates, but the most fundamental questions in understanding disease progression and protective host responses that are responsible for controlling Mtb infection still remain poorly resolved. Current TB treatment requires intense chemotherapy with several antimicrobials, while the only approved vaccine is the classical viable whole-cell based Bacille-Calmette-Guerin (BCG) that protects children from severe forms of TB, but fails to protect adults. Taken together, there is a growing need to conduct basic and applied research to develop novel vaccine strategies against TB. This review is focused on the discussion surrounding current strategies and innovations being explored to discover new protective antigens, adjuvants, and delivery systems in the hopes of creating an efficacious TB vaccine. PMID:23230563

  18. Developments in L2-based human papillomavirus (HPV) vaccines.

    Science.gov (United States)

    Schellenbacher, Christina; Roden, Richard B S; Kirnbauer, Reinhard

    2017-03-02

    Infections with sexually transmitted high-risk Human Papillomavirus (hrHPV), of which there are at least 15 genotypes, are responsible for a tremendous disease burden by causing cervical, and subsets of other ano-genital and oro-pharyngeal carcinomas, together representing 5% of all cancer cases worldwide. HPV subunit vaccines consisting of virus-like particles (VLP) self-assembled from major capsid protein L1 plus adjuvant have been licensed. Prophylactic vaccinations with the 2-valent (HPV16/18), 4-valent (HPV6/11/16/18), or 9-valent (HPV6/11/16/18/31/33/45/52/58) vaccine induce high-titer neutralizing antibodies restricted to the vaccine types that cause up to 90% of cervical carcinomas, a subset of other ano-genital and oro-pharyngeal cancers and 90% of benign ano-genital warts (condylomata). The complexity of manufacturing multivalent L1-VLP vaccines limits the number of included VLP types and thus the vaccines' spectrum of protection, leaving a panel of oncogenic mucosal HPV unaddressed. In addition, current vaccines do not protect against cutaneous HPV types causing benign skin warts, or against beta-papillomavirus (betaPV) types implicated in the development of non-melanoma skin cancer (NMSC) in immunosuppressed patients. In contrast with L1-VLP, the minor capsid protein L2 contains type-common epitopes that induce low-titer yet broadly cross-neutralizing antibodies to heterologous PV types and provide cross-protection in animal challenge models. Efforts to increase the low immunogenicity of L2 (poly)-peptides and thereby to develop broader-spectrum HPV vaccines are the focus of this review. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. TBVAC2020: Advancing Tuberculosis Vaccines from Discovery to Clinical Development

    Directory of Open Access Journals (Sweden)

    Stefan H. E. Kaufmann

    2017-10-01

    Full Text Available TBVAC2020 is a research project supported by the Horizon 2020 program of the European Commission (EC. It aims at the discovery and development of novel tuberculosis (TB vaccines from preclinical research projects to early clinical assessment. The project builds on previous collaborations from 1998 onwards funded through the EC framework programs FP5, FP6, and FP7. It has succeeded in attracting new partners from outstanding laboratories from all over the world, now totaling 40 institutions. Next to the development of novel vaccines, TB biomarker development is also considered an important asset to facilitate rational vaccine selection and development. In addition, TBVAC2020 offers portfolio management that provides selection criteria for entry, gating, and priority settings of novel vaccines at an early developmental stage. The TBVAC2020 consortium coordinated by TBVI facilitates collaboration and early data sharing between partners with the common aim of working toward the development of an effective TB vaccine. Close links with funders and other consortia with shared interests further contribute to this goal.

  20. Current status of syphilis vaccine development: need, challenges, prospects.

    Science.gov (United States)

    Cameron, Caroline E; Lukehart, Sheila A

    2014-03-20

    Syphilis is a multistage disease caused by the invasive spirochete Treponema pallidum subsp. pallidum. Despite inexpensive and effective antibiotic therapy, syphilis remains a prevalent disease in developing countries and has re-emerged as a public health threat in developed nations. In addition to the medical burden imparted by infectious syphilis, congenital syphilis is considered the most significant infectious disease affecting fetuses and newborns worldwide, and individuals afflicted with syphilis have an enhanced risk for HIV transmission and acquisition. The global disease burden of syphilis and failure of decades of public health efforts to stem the incidence of disease highlight the need for an effective syphilis vaccine. Although challenges associated with T. pallidum research have impeded understanding of this pathogen, the existence of a relevant animal model has enabled insight into the correlates of disease protection. Complete protection against infection has been achieved in the animal model using an extended immunization regimen of γ-irradiated T. pallidum, demonstrating the importance of treponemal surface components in generation of protective immunity and the feasibility of syphilis vaccine development. Syphilis is a prime candidate for development of a successful vaccine due to the (1) research community's accumulated knowledge of immune correlates of protection; (2) existence of a relevant animal model that enables effective pre-clinical analyses; (3) universal penicillin susceptibility of T. pallidum which enhances the attractiveness of clinical vaccine trials; and (4) significant public health benefit a vaccine would have on reduction of infectious/congenital syphilis and HIV rates. Critical personnel, research and market gaps need to be addressed before the goal of a syphilis vaccine can be realized, including recruitment of additional researchers to the T. pallidum research field with a proportional increase in research funding

  1. Cross-stage immunity for malaria vaccine development.

    Science.gov (United States)

    Nahrendorf, Wiebke; Scholzen, Anja; Sauerwein, Robert W; Langhorne, Jean

    2015-12-22

    A vaccine against malaria is urgently needed for control and eventual eradication. Different approaches are pursued to induce either sterile immunity directed against pre-erythrocytic parasites or to mimic naturally acquired immunity by controlling blood-stage parasite densities and disease severity. Pre-erythrocytic and blood-stage malaria vaccines are often seen as opposing tactics, but it is likely that they have to be combined into a multi-stage malaria vaccine to be optimally safe and effective. Since many antigenic targets are shared between liver- and blood-stage parasites, malaria vaccines have the potential to elicit cross-stage protection with immune mechanisms against both stages complementing and enhancing each other. Here we discuss evidence from pre-erythrocytic and blood-stage subunit and whole parasite vaccination approaches that show that protection against malaria is not necessarily stage-specific. Parasites arresting at late liver-stages especially, can induce powerful blood-stage immunity, and similarly exposure to blood-stage parasites can afford pre-erythrocytic immunity. The incorporation of a blood-stage component into a multi-stage malaria vaccine would hence not only combat breakthrough infections in the blood should the pre-erythrocytic component fail to induce sterile protection, but would also actively enhance the pre-erythrocytic potency of this vaccine. We therefore advocate that future studies should concentrate on the identification of cross-stage protective malaria antigens, which can empower multi-stage malaria vaccine development. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  2. Developing VISO: Vaccine Information Statement Ontology for patient education.

    Science.gov (United States)

    Amith, Muhammad; Gong, Yang; Cunningham, Rachel; Boom, Julie; Tao, Cui

    2015-01-01

    To construct a comprehensive vaccine information ontology that can support personal health information applications using patient-consumer lexicon, and lead to outcomes that can improve patient education. The authors composed the Vaccine Information Statement Ontology (VISO) using the web ontology language (OWL). We started with 6 Vaccine Information Statement (VIS) documents collected from the Centers for Disease Control and Prevention (CDC) website. Important and relevant selections from the documents were recorded, and knowledge triples were derived. Based on the collection of knowledge triples, the meta-level formalization of the vaccine information domain was developed. Relevant instances and their relationships were created to represent vaccine domain knowledge. The initial iteration of the VISO was realized, based on the 6 Vaccine Information Statements and coded into OWL2 with Protégé. The ontology consisted of 132 concepts (classes and subclasses) with 33 types of relationships between the concepts. The total number of instances from classes totaled at 460, along with 429 knowledge triples in total. Semiotic-based metric scoring was applied to evaluate quality of the ontology.

  3. Reverse Genetics Approaches for the Development of Influenza Vaccines

    Science.gov (United States)

    Nogales, Aitor; Martínez-Sobrido, Luis

    2016-01-01

    Influenza viruses cause annual seasonal epidemics and occasional pandemics of human respiratory disease. Influenza virus infections represent a serious public health and economic problem, which are most effectively prevented through vaccination. However, influenza viruses undergo continual antigenic variation, which requires either the annual reformulation of seasonal influenza vaccines or the rapid generation of vaccines against potential pandemic virus strains. The segmented nature of influenza virus allows for the reassortment between two or more viruses within a co-infected cell, and this characteristic has also been harnessed in the laboratory to generate reassortant viruses for their use as either inactivated or live-attenuated influenza vaccines. With the implementation of plasmid-based reverse genetics techniques, it is now possible to engineer recombinant influenza viruses entirely from full-length complementary DNA copies of the viral genome by transfection of susceptible cells. These reverse genetics systems have provided investigators with novel and powerful approaches to answer important questions about the biology of influenza viruses, including the function of viral proteins, their interaction with cellular host factors and the mechanisms of influenza virus transmission and pathogenesis. In addition, reverse genetics techniques have allowed the generation of recombinant influenza viruses, providing a powerful technology to develop both inactivated and live-attenuated influenza vaccines. In this review, we will summarize the current knowledge of state-of-the-art, plasmid-based, influenza reverse genetics approaches and their implementation to provide rapid, convenient, safe and more effective influenza inactivated or live-attenuated vaccines. PMID:28025504

  4. Accelerating Vaccine Formulation Development Using Design of Experiment Stability Studies.

    Science.gov (United States)

    Ahl, Patrick L; Mensch, Christopher; Hu, Binghua; Pixley, Heidi; Zhang, Lan; Dieter, Lance; Russell, Ryann; Smith, William J; Przysiecki, Craig; Kosinski, Mike; Blue, Jeffrey T

    2016-10-01

    Vaccine drug product thermal stability often depends on formulation input factors and how they interact. Scientific understanding and professional experience typically allows vaccine formulators to accurately predict the thermal stability output based on formulation input factors such as pH, ionic strength, and excipients. Thermal stability predictions, however, are not enough for regulators. Stability claims must be supported by experimental data. The Quality by Design approach of Design of Experiment (DoE) is well suited to describe formulation outputs such as thermal stability in terms of formulation input factors. A DoE approach particularly at elevated temperatures that induce accelerated degradation can provide empirical understanding of how vaccine formulation input factors and interactions affect vaccine stability output performance. This is possible even when clear scientific understanding of particular formulation stability mechanisms are lacking. A DoE approach was used in an accelerated 37(°)C stability study of an aluminum adjuvant Neisseria meningitidis serogroup B vaccine. Formulation stability differences were identified after only 15 days into the study. We believe this study demonstrates the power of combining DoE methodology with accelerated stress stability studies to accelerate and improve vaccine formulation development programs particularly during the preformulation stage. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  5. Development of high-yield influenza B virus vaccine viruses.

    Science.gov (United States)

    Ping, Jihui; Lopes, Tiago J S; Neumann, Gabriele; Kawaoka, Yoshihiro

    2016-12-20

    The burden of human infections with influenza A and B viruses is substantial, and the impact of influenza B virus infections can exceed that of influenza A virus infections in some seasons. Over the past few decades, viruses of two influenza B virus lineages (Victoria and Yamagata) have circulated in humans, and both lineages are now represented in influenza vaccines, as recommended by the World Health Organization. Influenza B virus vaccines for humans have been available for more than half a century, yet no systematic efforts have been undertaken to develop high-yield candidates. Therefore, we screened virus libraries possessing random mutations in the six "internal" influenza B viral RNA segments [i.e., those not encoding the major viral antigens, hemagglutinin (HA) and neuraminidase NA)] for mutants that confer efficient replication. Candidate viruses that supported high yield in cell culture were tested with the HA and NA genes of eight different viruses of the Victoria and Yamagata lineages. We identified combinations of mutations that increased the titers of candidate vaccine viruses in mammalian cells used for human influenza vaccine virus propagation and in embryonated chicken eggs, the most common propagation system for influenza viruses. These influenza B virus vaccine backbones can be used for improved vaccine virus production.

  6. Development of a Vaccine against Escherichia coli Urinary Tract Infections

    Directory of Open Access Journals (Sweden)

    Harry L. T. Mobley

    2015-12-01

    Full Text Available Urinary tract infection (UTI is the second most common infection in humans after those involving the respiratory tract. This results not only in huge annual economic costs, but in decreased workforce productivity and high patient morbidity. Most infections are caused by uropathogenic Escherichia coli (UPEC. Antibiotic treatment is generally effective for eradication of the infecting strain; however, documentation of increasing antibiotic resistance, allergic reaction to certain pharmaceuticals, alteration of normal gut flora, and failure to prevent recurrent infections represent significant barriers to treatment. As a result, approaches to prevent UTI such as vaccination represent a gap that must be addressed. Our laboratory has made progress toward development of a preventive vaccine against UPEC. The long-term research goal is to prevent UTIs in women with recurrent UTIs. Our objective has been to identify the optimal combination of protective antigens for inclusion in an effective UTI vaccine, optimal adjuvant, optimal dose, and optimal route of delivery. We hypothesized that a multi-subunit vaccine elicits antibody that protects against experimental challenge with UPEC strains. We have systematically identified four antigens that can individually protect experimentally infected mice from colonization of the bladder and/or kidneys by UPEC when administered intranasally with cholera toxin (CT as an adjuvant. To advance the vaccine for utility in humans, we will group the individual antigens, all associated with iron acquisition (IreA, Hma, IutA, FyuA, into an effective combination to establish a multi-subunit vaccine. We demonstrated for all four vaccine antigens that antigen-specific serum IgG represents a strong correlate of protection in vaccinated mice. High antibody titers correlate with low colony forming units (CFUs of UPEC following transurethral challenge of vaccinated mice. However, the contribution of cell-mediated immunity cannot

  7. Lock in, the state and vaccine development: lessons from the history of the polio vaccines

    NARCIS (Netherlands)

    Blume, S.S.

    2005-01-01

    Over the past two decades pharmaceutical industry interest in the development of vaccines against infectious diseases has grown. At the same time various partnerships and mechanisms have been established in order to reconcile the interests of private industry with the needs of public health systems

  8. MALVAC 2012 scientific forum: accelerating development of second-generation malaria vaccines

    Science.gov (United States)

    2012-01-01

    The World Health Organization (WHO) convened a malaria vaccines committee (MALVAC) scientific forum from 20 to 21 February 2012 in Geneva, Switzerland, to review the global malaria vaccine portfolio, to gain consensus on approaches to accelerate second-generation malaria vaccine development, and to discuss the need to update the vision and strategic goal of the Malaria Vaccine Technology Roadmap. This article summarizes the forum, which included reviews of leading Plasmodium falciparum vaccine candidates for pre-erythrocytic vaccines, blood-stage vaccines, and transmission-blocking vaccines. Other major topics included vaccine candidates against Plasmodium vivax, clinical trial site capacity development in Africa, trial design considerations for a second-generation malaria vaccine, adjuvant selection, and regulatory oversight functions including vaccine licensure. PMID:23140365

  9. Prevention and control of influenza and dengue through vaccine development.

    Science.gov (United States)

    Greenberg, David P; Robertson, Corwin A; Gordon, Daniel M

    2013-08-01

    Influenza and dengue are viral illnesses of global public health importance, especially among children. Accordingly, these diseases have been the focus of efforts to improve their prevention and control. Influenza vaccination offers the best protection against clinical disease caused by strains contained within the specific year's formulation. It is not uncommon for there to be a mismatch between vaccine strains and circulating strains, particularly with regards to the B lineages. For more than a decade, two distinct lineages of influenza B (Yamagata and Victoria) have co-circulated in the US with varying frequencies, but trivalent influenza vaccines contain only one B-lineage strain and do not offer adequate protection against the alternate B-lineage. Quadrivalent influenza vaccines (QIVs), containing two A strains (H1N1 and H3N2) and two B strains (one from each lineage) have been developed to help protect against the four strains predicted to be the most likely to be circulating. The QIV section of this article discusses epidemiology of pediatric influenza, importance of influenza B in children, potential benefits of QIV, and new quadrivalent vaccines. In contrast to influenza, a vaccine against dengue is not yet available in spite of many decades of research and development. A global increase in reports of dengue fever (DF) and its more severe presentations, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS), suggest that US physicians will increasingly encounter patients with this disease. Similarities of the early signs and symptoms of influenza and dengue and the differences in disease management necessitates a better understanding of the epidemiology, clinical presentation, management, and prevention of DF by US physicians, including pediatricians. The article also provides a brief overview of dengue and discusses dengue vaccine development. Copyright 2013, SLACK Incorporated.

  10. [Immunology of tuberculosis and current status of vaccine development].

    Science.gov (United States)

    Ulrichs, T

    2008-03-01

    Even 125 year after the discovery of Mycobacterium tuberculosis as the aetiological agent of tuberculosis by Robert Koch, tuberculosis is still a global health emergency according to WHO. The high infection rate with M. tuberculosis that persists in the human host until a weakened host immune system allows a reactivation and complicated and expensive antituberculous chemotherapy urgently demand the development of new vaccines. Increasing numbers of multidrug-resistant tuberculosis, especially in the successor states of the former Soviet Union and China, further complicate an efficient tuberculosis control. For decades, there was no new release of an antituberculous drug to efficiently fight tuberculosis. Hence, also drug development has to keep up with the development of resistance by the pathogen. The following review describes the immune response to M. tuberculosis infection and the deduction of strategies for novel vaccines. Thanks to international financial support, several new vaccine candidates are already in the pipeline and close to clinical testing phases.

  11. Development of an Alternative Modified Live Influenza B Virus Vaccine

    Science.gov (United States)

    Finch, Courtney; Sutton, Troy; Obadan, Adebimpe; Aguirre, Isabel; Wan, Zhimin; Lopez, Diego; Geiger, Ginger; Gonzalez-Reiche, Ana Silvia; Ferreri, Lucas

    2017-01-01

    ABSTRACT Influenza B virus (IBV) is considered a major human pathogen, responsible for seasonal epidemics of acute respiratory illness. Two antigenically distinct IBV hemagglutinin (HA) lineages cocirculate worldwide with little cross-reactivity. Live attenuated influenza virus (LAIV) vaccines have been shown to provide better cross-protective immune responses than inactivated vaccines by eliciting local mucosal immunity and systemic B cell- and T cell-mediated memory responses. We have shown previously that incorporation of temperature-sensitive (ts) mutations into the PB1 and PB2 subunits along with a modified HA epitope tag in the C terminus of PB1 resulted in influenza A viruses (IAV) that are safe and effective as modified live attenuated (att) virus vaccines (IAV att). We explored whether analogous mutations in the IBV polymerase subunits would result in a stable virus with an att phenotype. The PB1 subunit of the influenza B/Brisbane/60/2008 strain was used to incorporate ts mutations and a C-terminal HA tag. Such modifications resulted in a B/Bris att strain with ts characteristics in vitro and an att phenotype in vivo. Vaccination studies in mice showed that a single dose of the B/Bris att candidate stimulated sterilizing immunity against lethal homologous challenge and complete protection against heterologous challenge. These studies show the potential of an alternative LAIV platform for the development of IBV vaccines. IMPORTANCE A number of issues with regard to the effectiveness of the LAIV vaccine licensed in the United States (FluMist) have arisen over the past three seasons (2013–2014, 2014–2015, and 2015–2016). While the reasons for the limited robustness of the vaccine-elicited immune response remain controversial, this problem highlights the critical importance of continued investment in LAIV development and creates an opportunity to improve current strategies so as to develop more efficacious vaccines. Our laboratory has developed an

  12. Development of an Alternative Modified Live Influenza B Virus Vaccine.

    Science.gov (United States)

    Santos, Jefferson J S; Finch, Courtney; Sutton, Troy; Obadan, Adebimpe; Aguirre, Isabel; Wan, Zhimin; Lopez, Diego; Geiger, Ginger; Gonzalez-Reiche, Ana Silvia; Ferreri, Lucas; Perez, Daniel R

    2017-06-15

    Influenza B virus (IBV) is considered a major human pathogen, responsible for seasonal epidemics of acute respiratory illness. Two antigenically distinct IBV hemagglutinin (HA) lineages cocirculate worldwide with little cross-reactivity. Live attenuated influenza virus (LAIV) vaccines have been shown to provide better cross-protective immune responses than inactivated vaccines by eliciting local mucosal immunity and systemic B cell- and T cell-mediated memory responses. We have shown previously that incorporation of temperature-sensitive ( ts ) mutations into the PB1 and PB2 subunits along with a modified HA epitope tag in the C terminus of PB1 resulted in influenza A viruses (IAV) that are safe and effective as modified live attenuated ( att ) virus vaccines (IAV att ). We explored whether analogous mutations in the IBV polymerase subunits would result in a stable virus with an att phenotype. The PB1 subunit of the influenza B/Brisbane/60/2008 strain was used to incorporate ts mutations and a C-terminal HA tag. Such modifications resulted in a B/Bris att strain with ts characteristics in vitro and an att phenotype in vivo Vaccination studies in mice showed that a single dose of the B/Bris att candidate stimulated sterilizing immunity against lethal homologous challenge and complete protection against heterologous challenge. These studies show the potential of an alternative LAIV platform for the development of IBV vaccines. IMPORTANCE A number of issues with regard to the effectiveness of the LAIV vaccine licensed in the United States (FluMist) have arisen over the past three seasons (2013-2014, 2014-2015, and 2015-2016). While the reasons for the limited robustness of the vaccine-elicited immune response remain controversial, this problem highlights the critical importance of continued investment in LAIV development and creates an opportunity to improve current strategies so as to develop more efficacious vaccines. Our laboratory has developed an alternative

  13. Experimental animal modelling for TB vaccine development

    Directory of Open Access Journals (Sweden)

    Pere-Joan Cardona

    2017-03-01

    Full Text Available Research for a novel vaccine to prevent tuberculosis is an urgent medical need. The current vaccine, BCG, has demonstrated a non-homogenous efficacy in humans, but still is the gold standard to be improved upon. In general, the main indicator for testing the potency of new candidates in animal models is the reduction of the bacillary load in the lungs at the acute phase of the infection. Usually, this reduction is similar to that induced by BCG, although in some cases a weak but significant improvement can be detected, but none of candidates are able to prevent establishment of infection. The main characteristics of several laboratory animals are reviewed, reflecting that none are able to simulate the whole characteristics of human tuberculosis. As, so far, no surrogate of protection has been found, it is important to test new candidates in several models in order to generate convincing evidence of efficacy that might be better than that of BCG in humans. It is also important to investigate the use of “in silico” and “ex vivo” models to better understand experimental data and also to try to replace, or at least reduce and refine experimental models in animals.

  14. Evaluation of vaccines against enteric infections: a clinical and public health research agenda for developing countries

    Science.gov (United States)

    Clemens, John

    2011-01-01

    Enteric infections are a major cause of morbidity and mortality in developing countries. To date, vaccines have played a limited role in public health efforts to control enteric infections. Licensed vaccines exist for cholera and typhoid, but these vaccines are used primarily for travellers; and there are two internationally licensed vaccines for rotavirus, but they are mainly used in affluent countries. The reasons that enteric vaccines are little used in developing countries are multiple, and certainly include financial and political constraints. Also important is the need for more cogent evidence on the performance of enteric vaccines in developing country populations. A partial inventory of research questions would include: (i) does the vaccine perform well in the most relevant settings? (ii) does the vaccine perform well in all epidemiologically relevant age groups? (iii) is there adequate evidence of vaccine safety once the vaccines have been deployed in developing countries? (iv) how effective is the vaccine when given in conjunction with non-vaccine cointerventions? (v) what is the level of vaccine protection against all relevant outcomes? and (vi) what is the expected population level of vaccine protection, including both direct and herd vaccine protective effects? Provision of evidence addressing these questions will help expand the use of enteric vaccines in developing countries. PMID:21893543

  15. Development of replication-deficient adenovirus malaria vaccines.

    Science.gov (United States)

    Hollingdale, Michael R; Sedegah, Martha; Limbach, Keith

    2017-03-01

    Malaria remains a major threat to endemic populations and travelers, including military personnel to these areas. A malaria vaccine is feasible, as radiation attenuated sporozoites induce nearly 100% efficacy. Areas covered: This review covers current malaria clinical trials using adenoviruses and pre-clinical research. Heterologous prime-boost regimens, including replication-deficient human adenovirus 5 (HuAd5) carrying malaria antigens, are efficacious. However, efficacy appears to be adversely affected by pre-existing anti-HuAd5 antibodies. Current strategies focus on replacing HuAd5 with rarer human adenoviruses or adenoviruses isolated from non-human primates (NHPs). The chimpanzee adenovirus ChAd63 is undergoing evaluation in clinical trials including infants in malaria-endemic areas. Key antigens have been identified and are being used alone, in combination, or with protein subunit vaccines. Gorilla adenoviruses carrying malaria antigens are also currently being evaluated in preclinical models. These replacement adenovirus vectors will be successfully used to develop vaccines against malaria, as well as other infectious diseases. Expert commentary: Simplified prime-boost single shot regimens, dry-coated live vector vaccines or silicon microneedle arrays could be developed for malaria or other vaccines. Replacement vectors with similar or superior immunogenicity have rapidly advanced, and several are now in extensive Phase 2 and beyond in malaria as well as other diseases, notably Ebola.

  16. Overview of dendritic cell-based vaccine development for leishmaniasis.

    Science.gov (United States)

    Bagirova, M; Allahverdiyev, A M; Abamor, E S; Ullah, I; Cosar, G; Aydogdu, M; Senturk, H; Ergenoglu, B

    2016-11-01

    Leishmaniasis is one of the most serious vector-borne diseases in the world and is distributed over 98 countries. It is estimated that 350 million people are at risk for leishmaniasis. There are three different generation of vaccines that have been developed to provide immunity and protection against leishmaniasis. However, their use has been limited due to undesired side effects. These vaccines have also failed to provide effective and reliable protection and, as such, currently, there is no safe and effective vaccine for leishmaniasis. Dendritic cells (DCs) are a unique population of cells that come from bone marrow and become specialized to take up, process and present antigens to helper T cells in a mechanism similar to macrophages. By considering these significant features, DCs stimulated with different kinds of Leishmania antigens have been used in recent vaccine studies for leishmaniasis with promising results so far. In this review, we aim to review and combine the latest studies about this issue after defining potential problems in vaccine development for leishmaniasis and considering the importance of DCs in the immunopathogenesis of the disease. © 2016 John Wiley & Sons Ltd.

  17. Botulinum neurotoxin vaccines: Past history and recent developments.

    Science.gov (United States)

    Rusnak, Janice M; Smith, Leonard A

    2009-12-01

    Botulinum toxin may cause a neuroparalytic illness that may result in respiratory failure and require prolonged mechanical ventilation. As medical resources needed for supportive care of botulism in a bioterrorist event may quickly overwhelm the local healthcare systems, biodefense research efforts have been directed towards the development of a vaccine to prevent botulism. While human botulism has been caused only by toxin serotypes A, B, and E (rarely serotype F), all seven known immunologically distinct toxin serotypes (A - G) may potentially cause intoxication in humans from a bioterrorist event. A pentavalent (ABCDE) botulinum toxoid (PBT) has been administered as an investigation new drug (IND) to at-risk individuals for nearly 50 years. Due to declining immunogenicity of the PBT, research efforts have been directed at development of both improved (less local reactogenicity) botulinum toxoids and recombinant vaccines as potential vaccine candidates to replace the PBT.

  18. Development of Mucosal Vaccines Based on Lactic Acid Bacteria

    Science.gov (United States)

    Bermúdez-Humarán, Luis G.; Innocentin, Silvia; Lefèvre, Francois; Chatel, Jean-Marc; Langella, Philippe

    Today, sufficient data are available to support the use of lactic acid bacteria (LAB), notably lactococci and lactobacilli, as delivery vehicles for the development of new mucosal vaccines. These non-pathogenic Gram-positive bacteria have been safely consumed by humans for centuries in fermented foods. They thus constitute an attractive alternative to the attenuated pathogens (most popular live vectors actually studied) which could recover their pathogenic potential and are thus not totally safe for use in humans. This chapter reviews the current research and advances in the use of LAB as live delivery vectors of proteins of interest for the development of new safe mucosal vaccines. The use of LAB as DNA vaccine vehicles to deliver DNA directly to antigen-presenting cells of the immune system is also discussed.

  19. Respiratory Syncytial Virus: Current Progress in Vaccine Development

    Science.gov (United States)

    Rudraraju, Rajeev; Jones, Bart G.; Sealy, Robert; Surman, Sherri L.; Hurwitz, Julia L.

    2013-01-01

    Respiratory syncytial virus (RSV) is the etiological agent for a serious lower respiratory tract disease responsible for close to 200,000 annual deaths worldwide. The first infection is generally most severe, while re-infections usually associate with a milder disease. This observation and the finding that re-infection risks are inversely associated with neutralizing antibody titers suggest that immune responses generated toward a first RSV exposure can significantly reduce morbidity and mortality throughout life. For more than half a century, researchers have endeavored to design a vaccine for RSV that can mimic or improve upon natural protective immunity without adverse events. The virus is herein described together with the hurdles that must be overcome to develop a vaccine and some current vaccine development approaches. PMID:23385470

  20. Schistosomiasis vaccine development: progress and prospects

    Directory of Open Access Journals (Sweden)

    NR Bergquist

    1998-01-01

    Full Text Available The undisputed, worldwide success of chemotherapy notwithstanding, schistosomiasis continues to defy control efforts in as much rapid reinfection demands repeated treatment, sometimes as often as once a year. There is thus a need for a complementary tool with effect for the longer term, notably a vaccine. International efforts in this direction have been ongoing for several decades but, until the recombinant DNA techniques were introduced, antigen production remained an unsurmountable bottleneck. Although animal experiments have been highly productive and are still much needed, they probably do not reflect the human situation adequately and real progress can not be expected until more is known about human immune responses to schistosome infection. It is well-known that irradiated cercariae consistently produce high levels of protection in experimental animals but, for various reasons, this proof of principle cannot be directly exploited. Research has instead been focussed on the identification and testing of specific schistosome antigens. This work has been quite successful and is already at the stage where clinical trials are called for. Preliminary results from coordinated in vitro laboratory and field epidemiological studies regarding the protective potential of several antigens support the initiation of such trials. A series of meetings, organized earlier this year in Cairo, Egypt, reviewed recent progress, selecteded suitable vaccine candidates and made firm recommendations for future action including pledging support for large-scale production according to good manufacturing practice (GMP and Phase I trials. Scientists at the American Centers for Disease Control and Prevention (CDC have drawn up a detailed research plan. The major financial support will come from USAID, Cairo, which has established a scientific advisory group of Egyptian scientists and representatives from current and previous international donors such as WHO, NIAID, the

  1. Malaria Vaccine Development and How External Forces Shape It: An Overview

    Directory of Open Access Journals (Sweden)

    Veronique Lorenz

    2014-06-01

    Full Text Available The aim of this paper is to analyse the current status and scientific value of malaria vaccine approaches and to provide a realistic prognosis for future developments. We systematically review previous approaches to malaria vaccination, address how vaccine efforts have developed, how this issue may be fixed, and how external forces shape vaccine development. Our analysis provides significant information on the various aspects and on the external factors that shape malaria vaccine development and reveal the importance of vaccine development in our society.

  2. Status of vaccine research and development for Campylobacter jejuni.

    Science.gov (United States)

    Riddle, Mark S; Guerry, Patricia

    2016-06-03

    Campylobacter jejuni is one of the leading causes of bacterial diarrhea worldwide and is associated with a number of sequelae, including Guillain-Barre Syndrome, reactive arthritis, irritable bowel syndrome and growth stunting/malnutrition. Vaccine development against C. jejuni is complicated by its antigenic diversity, a lack of small animal models, and a poor understanding of the bacterium's pathogenesis. Vaccine approaches have been limited to recombinant proteins, none of which have advanced beyond Phase I testing. Genomic analyses have revealed the presence of a polysaccharide capsule on C. jejuni. Given the success of capsule-conjugate vaccines for other mucosal pathogens of global importance, efforts to evaluate this established approach for C. jejuni are also being pursued. A prototypical capsule-conjugate vaccine has demonstrated efficacy against diarrheal disease in non-human primates and is currently in Phase I testing. In addition to proof of concept studies, more data on the global prevalence of capsular types, and a better understanding of the acute and chronic consequences of C. jejuni are needed to inform investments for a globally relevant vaccine. Copyright © 2016 World Health Organization. Published by Elsevier Ltd.. All rights reserved.

  3. Recent advances in canine leptospirosis: focus on vaccine development

    Directory of Open Access Journals (Sweden)

    Klaasen HLBM

    2015-06-01

    Full Text Available Henricus LBM (Eric Klaasen,1 Ben Adler2 1Global Companion Animals Research and Development, Merck Sharp and Dohme Animal Health, Boxmeer, the Netherlands; 2Department of Microbiology, Monash University, Clayton, VIC, Australia Abstract: Leptospirosis is a global infection of humans and animals caused by pathogenic Leptospira spp. Leptospirosis is a major zoonosis, with infection acquired from wild and domestic animals. It is also a significant cause of morbidity, mortality, and economic loss in production and companion animals. Leptospirosis in dogs is prevalent worldwide and as well as a cause of canine disease, it presents a zoonotic risk to human contacts. Canine leptospirosis does not differ greatly from the syndromes seen in other animal species, with hepatic, renal, and pulmonary involvement being the main manifestations. While the pathogenesis of disease is well documented at the whole animal level, the cellular and molecular basis remains obscure. Killed, whole-cell bacterin vaccines are licensed worldwide and have not changed greatly over the past several decades. Vaccine-induced immunity is restricted to serologically related serovars and is generally short-lived, necessitating annual revaccination. The appearance of new serovars as causes of canine leptospirosis requires constant epidemiological surveillance and tailoring of vaccines to cover emerging serovars. At the present time, there is no realistic prospect of alternative, non-bacterin vaccines in the foreseeable future. Keywords: canine leptospirosis, vaccines, diagnosis, epidemiology, pathogenesis

  4. Clinical vaccine development for H5N1 influenza.

    Science.gov (United States)

    Clegg, Christopher H; Rininger, Joseph A; Baldwin, Susan L

    2013-07-01

    H5N1 is a highly pathogenic avian influenza virus that can cause severe disease and death in humans. H5N1 is spreading rapidly in bird populations and there is great concern that this virus will begin to transmit between people and cause a global crisis. Vaccines are the cornerstone strategy for combating avian influenza but there are complex challenges for pandemic preparedness including the unpredictability of the vaccine target and the manufacturing requirement for rapid deployment. The less-than-optimal response against the 2009 H1N1 pandemic unmasked the limitations associated with influenza vaccine production and in 2010, the President's Council of Advisors on Science and Technology re-emphasized the need for new recombinant-based vaccines and adjuvants that can shorten production cycles, maximize immunogenicity and satisfy global demand. In this article, the authors review the efforts spent in developing an effective vaccine for H5N1 influenza and summarize clinical studies that highlight the progress made to date.

  5. Development of an Integrated Immunology and Vaccines Pharmacy Elective

    Directory of Open Access Journals (Sweden)

    Stephanie F James

    2017-07-01

    Full Text Available Objective: To describe an elective course on immunology and vaccines for pharmacy students that extends beyond basic immunization training. Design: A three credit-hour Immunology and Vaccines elective was developed and taught by an immunologist, policy research expert, and pharmacist. The learning objectives of the course included: understanding how the immune system works with vaccines to provide protection against infectious diseases, the history and policies involved in immunization practice, and how to counsel the vaccine hesitant individual. Classes were conducted using a variety of formats; group projects, lectures, films, literature reviews and guest speakers. An end-of-course evaluation was used to gauge student opinion on course value. Students were evaluated by four exams and a final group presentation. Conclusion: Students indicated that this course was valuable to their future pharmacy careers and provided insight into why people choose not to vaccinate and how they could use the course insight to properly educate such individuals. Conflict of Interest We declare no conflicts of interest or financial interests that the authors or members of their immediate families have in any product or service discussed in the manuscript, including grants (pending or received, employment, gifts, stock holdings or options, honoraria, consultancies, expert testimony, patents and royalties   Type: Note

  6. Animal models for dengue vaccine development and testing.

    Science.gov (United States)

    Na, Woonsung; Yeom, Minjoo; Choi, Il-Kyu; Yook, Heejun; Song, Daesub

    2017-07-01

    Dengue fever is a tropical endemic disease; however, because of climate change, it may become a problem in South Korea in the near future. Research on vaccines for dengue fever and outbreak preparedness are currently insufficient. In addition, because there are no appropriate animal models, controversial results from vaccine efficacy assessments and clinical trials have been reported. Therefore, to study the mechanism of dengue fever and test the immunogenicity of vaccines, an appropriate animal model is urgently needed. In addition to mouse models, more suitable models using animals that can be humanized will need to be constructed. In this report, we look at the current status of model animal construction and discuss which models require further development.

  7. The future for vaccine development against Entamoeba histolytica

    Science.gov (United States)

    Quach, Jeanie; St-Pierre, Joëlle; Chadee, Kris

    2014-01-01

    Entamoeba histolytica is the causative agent of amebiasis, one of the top three parasitic causes of mortality worldwide. In the majority of infected individuals, E. histolytica asymptomatically colonizes the large intestine, while in others, the parasite breaches the mucosal epithelial barrier to cause amebic colitis and can disseminate to soft organs to cause abscesses. Vaccinations using native and recombinant forms of the parasite Gal-lectin have been successful in protecting animals against intestinal amebiasis and amebic liver abscess. Protection against amebic liver abscesses has also been reported by targeting other E. histolytica components including the serine-rich protein and the 29-kDa-reductase antigen. To date, vaccines against the Gal-lectin hold the most promise but clinical trials will be required to validate its efficacy in humans. Here, we review the current strategies and future perspectives involved in the development of a vaccine against E. histolytica. PMID:24504133

  8. Viral Vectors for Use in the Development of Biodefense Vaccines

    National Research Council Canada - National Science Library

    Lee, John S; Hadjipanayis, Angela G; Parker, Michael D

    2005-01-01

    ... agents of bioterrorism or biowarfare. The use of viruses, for example adenovirus, vaccinia virus, and Venezuelan equine encephalitis virus, as vaccine-vectors has enabled researchers to develop effective means for countering the threat of bioterrorism and biowarfare. An overview of the different viral vectors and the threats they counter will be discussed.

  9. Economic evaluations of hepatitis B vaccination for developing countries

    NARCIS (Netherlands)

    Tu, H.A.T.; Woerdenbag, H.J.; Kane, S.; Riewpaiboon, A.; van Hulst, M.; Postma, M.J.

    Economic evaluations, in particular cost-effectiveness, are important determinants for policy makers and stakeholders involved in decision-making for health interventions. Up until now, most evaluations of cost-effectiveness of hepatitis B vaccination have been performed in developed countries.

  10. Systems Biology and the Development of Vaccines and Drugs for ...

    African Journals Online (AJOL)

    We conclude the paper highlighting the procedures encompassing the back end phase and discuss their application to the development of vaccines and drugs for malaria treatment. Note that, malaria is the cause of significant global morbidity and mortality with 300-500 million cases annually. Our aims are not ends, but a ...

  11. Development of lactococcal GEM-based pneumococcal vaccines

    NARCIS (Netherlands)

    Audouy, Sandrine A. L.; van Selm, Saskia; van Roosmalen, Maarten L.; Post, Eduard; Kanninga, Rolf; Neef, Jolanda; Estevao, Silvia; Nieuwenhuis, Edward E. S.; Adrian, Peter V.; Leenhouts, Kees; Hermans, Peter W. M.

    2007-01-01

    We report the development of a novel protein-based nasal vaccine against Streptococcus pneumoniae, in which three pneumococcal proteins were displayed on the surface of a non-recombinant, killed Lactococcus lactis-derived delivery system, called Gram-positive Enhancer Matrix (GEM). The GEM particles

  12. Nanostructures for the development of vaccines against avian ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    State-of-the-art technologies developed in two laboratories will be combined: nanotechnology and a new adjuvant. These approaches will allow simple production of nanoparticles that do not require any special containment, as opposed to traditional vaccines produced in embryonated eggs. This project is a collaboration ...

  13. Viral Vectors for Use in the Development of Biodefense Vaccines

    Science.gov (United States)

    2005-06-17

    development . . . . . . . . . . . . . . . . . . 1308 6. Anti-vector immune responses associated with virus-vectored vaccines...to influence the outcome of a local election. Another radical group in Japan, the Aum Shinrikyo, allegedly conducted research on BoNT, B. anthracis...aflotoxin and actively researched Clostridium perfringins, rotavirus , echovi- rus 71, and camelpox virus for use in biological warfare [2,3]. Their

  14. Live bacterial delivery systems for development of mucosal vaccines

    NARCIS (Netherlands)

    Thole, J.E.R.; Dalen, P.J. van; Havenith, C.E.G.; Pouwels, P.H.; Seegers, J.F.M.L.; Tielen, F.D.; Zee, M.D. van der; Zegers, N.D.; Shaw, M.

    2000-01-01

    By expression of foreign antigens in attenuated strains derived from bacterial pathogens and in non-pathogenic commensal bacteria, recombinant vaccines are being developed that aim to stimulate mucosal immunity. Recent advances in the pathogenesis and molecular biology of these bacteria have allowed

  15. Development of novel vaccines using DNA shuffling and screening strategies.

    Science.gov (United States)

    Locher, Christopher P; Soong, Nay Wei; Whalen, Robert G; Punnonen, Juha

    2004-02-01

    DNA shuffling and screening technologies recombine and evolve genes in vitro to rapidly obtain molecules with improved biological activity and fitness. In this way, genes from related strains are bred like plants or livestock and their successive progeny are selected. These technologies have also been called molecular breeding-directed molecular evolution. Recent developments in bioinformatics-assisted computer programs have facilitated the design, synthesis and analysis of DNA shuffled libraries of chimeric molecules. New applications in vaccine development are among the key features of DNA shuffling and screening technologies because genes from several strains or antigenic variants of pathogens can be recombined to create novel molecules capable of inducing immune responses that protect against infections by multiple strains of pathogens. In addition, molecules such as co-stimulatory molecules and cytokines have been evolved to have improved T-cell proliferation and cytokine production compared with the wild-type human molecules. These molecules can be used to immunomodulate vaccine responsiveness and have multiple applications in infectious diseases, cancer, allergy and autoimmunity. Moreover, DNA shuffling and screening technologies can facilitate process development of vaccine manufacturing through increased expression of recombinant polypeptides and viruses. Therefore, DNA shuffling and screening technologies can overcome some of the challenges that vaccine development currently faces.

  16. New Paradigms for HIV/AIDS Vaccine Development

    Science.gov (United States)

    Hansen, Scott G.; Lifson, Jeffrey D.

    2012-01-01

    HIV-1 and its simian counterpart SIV have been exquisitely tailored by evolution to evade host immunity. By virtue of specific adaptations that thwart individual innate or adaptive immune mechanisms, and an overall replication strategy that provides for rapid establishment of a large, systemic viral population, capable of dynamic adaptation to almost all immune selection pressures, these viruses, once established, almost invariably stay one step ahead of the host, and in the vast majority of infected individuals, replicate indefinitely. Although many of vaccine approaches tested to date have been able to enhance the magnitude of the immune responses to HIV/SIV infection, most of these responses, whether cellular or humoral in nature, have largely failed to be both effectively anti-viral and targeted such that fully functional escape variants are not easily selected. Recent advances, however, have provided strong evidence that the initial stages of infection following mucosal transmission of these viruses are more vulnerable to immune intervention, and have led to the development of vaccine strategies that elicit responses able to effectively intervene in these early stages of infection, either preventing acquisition of infection or by establishing early, stringent, and durable control. Here, we place HIV/AIDS vaccine development in the context of the basic immunobiology of HIV/SIV, review the evidence for the vulnerability of early infection to immunity, and discuss how these newly recognized immune vulnerabilities might be exploited for the development of an effective HIV/AIDS vaccine. PMID:21942424

  17. Development of oral microencapsulated forms for delivering viral vaccines.

    Science.gov (United States)

    Nechaeva, Elena

    2002-10-01

    Rapid development in biotechnology during the last decade has allowed novel ideas in the development of antiviral vaccines to be considered and provides interesting technological approaches to their realization. Designing of microencapsulated forms for delivering bacterial and viral antigens or antigenic complexes using biodegradable biopolymers is an important novel direction. This approach involves the production of polymeric spherical particles with a diameter of 1 microm to 3 mm, containing isolated viral antigens or whole viral particles. Microencapsulated antigens administered orally are protected from low pH values of the gastric juice, bile acids, their salts and proteolytic enzymes of the gastrointestinal tract. The ability to drastically potentiate the immune response to encapsulated antigens, together with the ability to penetrate into the intestinal and respiratory mucosae upon oral and tracheal administrations, respectively, with induction of local and systemic immune reactions are the special merits of such polymers. However, the majority of data on microencapsulated viral vaccines has so far been obtained in animal models, as well as a limited number of studies on the protective effect they elicit. Certain success in the development of vaccines against a number of human viral infections, such as hepatitis B, cytomegalovirus and rotavirus, gives hope to successful completion of this research. Presumably, such vaccines will be safe and innocuous, simple in administration and capable of inducing both the systemic and local immune responses at the primary portal of viral infection.

  18. Vaccine safety monitoring systems in developing countries: an example of the Vietnam model.

    Science.gov (United States)

    Ali, Mohammad; Rath, Barbara; Thiem, Vu Dinh

    2015-01-01

    Only few health intervention programs have been as successful as vaccination programs with respect to preventing morbidity and mortality in developing countries. However, the success of a vaccination program is threatened by rumors and misunderstanding about the risks of vaccines. It is short-sighted to plan the introduction of vaccines into developing countries unless effective vaccine safety monitoring systems are in place. Such systems that track adverse events following immunization (AEFI) is currently lacking in most developing countries. Therefore, any rumor may affect the entire vaccination program. Public health authorities should implement the safety monitoring system of vaccines, and disseminate safety issues in a proactive mode. Effective safety surveillance systems should allow for the conduct of both traditional and alternative epidemiologic studies through the use of prospective data sets. The vaccine safety data link implemented in Vietnam in mid-2002 indicates that it is feasible to establish a vaccine safety monitoring system for the communication of vaccine safety in developing countries. The data link provided the investigators an opportunity to evaluate AEFI related to measles vaccine. Implementing such vaccine safety monitoring system is useful in all developing countries. The system should be able to make objective and clear communication regarding safety issues of vaccines, and the data should be reported to the public on a regular basis for maintaining their confidence in vaccination programs.

  19. Apicomplexan profilins in vaccine development applied to bovine neosporosis.

    Science.gov (United States)

    Mansilla, Florencia C; Capozzo, Alejandra V

    2017-12-01

    Neospora caninum, an intracellular protozoan parasite from the phylum Apicomplexa, is the etiologic agent of neosporosis, a disease considered as a major cause of reproductive loss in cattle and neuromuscular disease in dogs. Bovine neosporosis has a great economic impact in both meat and dairy industries, related to abortion, premature culling and reduced milk yields. Although many efforts have been made to restrain bovine neosporosis, there are still no efficacious control methods. Many vaccine-development studies focused in the apicomplexan proteins involved in the adhesion and invasion of the host cell. Among these proteins, profilins have recently emerged as potential vaccine antigens or even adjuvant candidates for several diseases caused by apicomplexan parasites. Profilins bind Toll-like receptors 11 and 12 initiating MyD88 signaling, that triggers IL-12 and IFN-γ production, which may promote protection against infection. Here we summarized the state-of-the-art of novel vaccine development based on apicomplexan profilins applied as antigens or adjuvants, and delved into recent advances on N. caninum vaccines using profilin in the mouse model and in cattle. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Ebola virus: immune mechanisms of protection and vaccine development.

    Science.gov (United States)

    Nyamathi, Adeline M; Fahey, John L; Sands, Heather; Casillas, Adrian M

    2003-04-01

    Vaccination is one of our most powerful antiviral strategies. Despite the emergence of deadly viruses such as Ebola virus, vaccination efforts have focused mainly on childhood communicable diseases. Although Ebola virus was once believed to be limited to isolated outbreaks in distant lands, forces of globalization potentiate outbreaks anywhere in the world through incidental transmission. Moreover, since this virus has already been transformed into weapon-grade material, the potential exists for it to be used as a biological weapon with catastrophic consequences for any population vulnerable to attack. Ebola hemorrhagic fever (EHF) is a syndrome that can rapidly lead to death within days of symptom onset. The disease directly affects the immune system and vascular bed, with correspondingly high mortality rates. Patients with severe disease produce dangerously high levels of inflammatory cytokines, which destroy normal tissue and microcirculation, leading to profound capillary leakage, renal failure, and disseminated intravascular coagulation. Vaccine development has been fraught with obstacles, primarily of a biosafety nature. Case reports of acutely ill patients with EHF showing improvement with the transfusion of convalescent plasma are at odds with animal studies demonstrating further viral replication with the same treatment. Using mRNA extracted from bone marrow of Ebola survivors, human monoclonal antibodies against Ebola virus surface protein have been experimentally produced and now raise the hope for the development of a safe vaccine.

  1. Humoral Immunity to Primary Smallpox Vaccination: Impact of Childhood versus Adult Immunization on Vaccinia Vector Vaccine Development in Military Populations.

    Science.gov (United States)

    Slike, Bonnie M; Creegan, Matthew; Marovich, Mary; Ngauy, Viseth

    2017-01-01

    Modified Vaccinia virus has been shown to be a safe and immunogenic vector platform for delivery of HIV vaccines. Use of this vector is of particular importance to the military, with the implementation of a large scale smallpox vaccination campaign in 2002 in active duty and key civilian personnel in response to potential bioterrorist activities. Humoral immunity to smallpox vaccination was previously shown to be long lasting (up to 75 years) and protective. However, using vaccinia-vectored vaccine delivery for other diseases on a background of anti-vector antibodies (i.e. pre-existing immunity) may limit their use as a vaccine platform, especially in the military. In this pilot study, we examined the durability of vaccinia antibody responses in adult primary vaccinees in a healthy military population using a standard ELISA assay and a novel dendritic cell neutralization assay. We found binding and neutralizing antibody (NAb) responses to vaccinia waned after 5-10 years in a group of 475 active duty military, born after 1972, who were vaccinated as adults with Dryvax®. These responses decreased from a geometric mean titer (GMT) of 250 to baseline (vaccination. This contrasted with a comparator group of adults, ages 35-49, who were vaccinated with Dryvax® as children. In the childhood vaccinees, titers persisted for >30 years with a GMT of 210 (range 112-3234). This data suggests limited durability of antibody responses in adult vaccinees compared to those vaccinated in childhood and further that adult vaccinia recipients may benefit similarly from receipt of a vaccinia based vaccine as those who are vaccinia naïve. Our findings may have implications for the smallpox vaccination schedule and support the ongoing development of this promising viral vector in a military vaccination program.

  2. Development of a VLP-based HCV vaccine candidate

    OpenAIRE

    Fernandes, Marina Isabel Ferreira

    2016-01-01

    Tese de mestrado, Biologia Molecular e Genética, Universidade de Lisboa, Faculdade de Ciências, 2016 The Hepatitis C Virus (HCV) infects approximately 3% of the world population, being one of the major causes of liver cirrhosis and hepatocellular carcinoma. The development of safe, effective and affordable prophylactic and therapeutic vaccines against HCV has become an important medical priority; however, there are many obstacles to its development. In recent years, strategies of viral ant...

  3. Roads to the development of improved pertussis vaccines paved by immunology

    Science.gov (United States)

    Brummelman, Jolanda; Wilk, Mieszko M.; Han, Wanda G.H.; van Els, Cécile A.C.M.; Mills, Kingston H.G.

    2015-01-01

    Current acellular pertussis vaccines have various shortcomings, which may contribute to their suboptimal efficacy and waning immunity in vaccinated populations. This calls for the development of new pertussis vaccines capable of inducing long-lived protective immunity. Immunization with whole cell pertussis vaccines and natural infection with Bordetella pertussis induce distinct and more protective immune responses when compared with immunization with acellular pertussis vaccines. Therefore, the immune responses induced with whole cell vaccine or after infection can be used as a benchmark for the development of third-generation vaccines against pertussis. Here, we review the literature on the immunology of B. pertussis infection and vaccination and discuss the lessons learned that will help in the design of improved pertussis vaccines. PMID:26347400

  4. Development, Production, and Postmarketing Surveillance of Hepatitis A Vaccines in China

    Science.gov (United States)

    Cui, Fuqiang; Liang, Xiaofeng; Wang, Fuzhen; Zheng, Hui; Hutin, Yvan J; Yang, Weizhong

    2014-01-01

    China has long experience using live attenuated and inactivated vaccines against hepatitis A virus (HAV) infection. We summarize this experience and provide recent data on adverse events after immunization (AEFIs) with hepatitis A vaccines in China. We reviewed the published literature (in Chinese and English) and the published Chinese regulatory documents on hepatitis A vaccine development, production, and postmarketing surveillance of AEFI. We described the safety, immunogenicity, and efficacy of hepatitis A vaccines and horizontal transmission of live HAV vaccine in China. In clinical trials, live HAV vaccine was associated with fever (0.4%–5% of vaccinees), rash (0%–1.1%), and elevated alanine aminotransferase (0.015%). Inactivated HAV vaccine was associated with fever (1%–8%), but no serious AEFIs were reported. Live HAV vaccine had seroconversion rates of 83% to 91%, while inactivated HAV vaccine had seroconversion rates of 95% to 100%. Community trials showed efficacy rates of 90% to 95% for live HAV and 95% to 100% for inactivated HAV vaccine. Postmarketing surveillance showed that HAV vaccination resulted in an AEFI incidence rate of 34 per million vaccinees, which accounted for 0.7% of adverse events reported to the China AEFI monitoring system. There was no difference in AEFI rates between live and inactivated HAV vaccines. Live and inactivated HAV vaccines manufactured in China were immunogenic, effective, and safe. Live HAV vaccine had substantial horizontal transmission due to vaccine virus shedding; thus, further monitoring of the safety of virus shedding is warranted. PMID:24681843

  5. Immune Response to Coccidioidomycosis and the Development of a Vaccine

    Directory of Open Access Journals (Sweden)

    Natalia Castro-Lopez

    2017-03-01

    Full Text Available Coccidioidomycosis is a fungal infection caused by Coccidioides posadasii and Coccidioides immitis. It is estimated that 150,000 new infections occur in the United States each year. The incidence of this infection continues to rise in endemic regions. There is an urgent need for the development of better therapeutic drugs and a vaccine against coccidioidomycosis. This review discusses the features of host innate and adaptive immune responses to Coccidioides infection. The focus is on the recent advances in the immune response and host-pathogen interactions, including the recognition of spherules by the host and defining the signal pathways that guide the development of the adaptive T-cell response to Coccidioides infection. Also discussed is an update on progress in developing a vaccine against these fungal pathogens.

  6. Protein conjugate polysaccharide vaccines: Challenges in development and global implementation

    Directory of Open Access Journals (Sweden)

    Manisha Nair

    2012-01-01

    Replacement by nonvaccine serotypes;capsule switching;time duration of the antibody protective effect following vaccination;costs of the vaccines, programme costs, lack of knowledge of the disease burden, and targeting population groups for vaccination.

  7. Workshop report: Malaria vaccine development in Europe--preparing for the future.

    Science.gov (United States)

    Viebig, Nicola K; D'Alessio, Flavia; Draper, Simon J; Sim, B Kim Lee; Mordmüller, Benjamin; Bowyer, Paul W; Luty, Adrian J F; Jungbluth, Stefan; Chitnis, Chetan E; Hill, Adrian V S; Kremsner, Peter; Craig, Alister G; Kocken, Clemens H M; Leroy, Odile

    2015-11-17

    The deployment of a safe and effective malaria vaccine will be an important tool for the control of malaria and the reduction in malaria deaths. With the launch of the 2030 Malaria Vaccine Technology Roadmap, the malaria community has updated the goals and priorities for the development of such a vaccine and is now paving the way for a second phase of malaria vaccine development. During a workshop in Brussels in November 2014, hosted by the European Vaccine Initiative, key players from the European, North American and African malaria vaccine community discussed European strategies for future malaria vaccine development in the global context. The recommendations of the European malaria community should guide researchers, policy makers and funders of global health research and development in fulfilling the ambitious goals set in the updated Malaria Vaccine Technology Roadmap. Copyright © 2015.

  8. Mapping and analysis of West Nile virus-specific monoclonal antibodies: prospects for vaccine development

    NARCIS (Netherlands)

    Throsby, Mark; ter Meulen, Jan; Geuijen, Cecile; Goudsmit, Jaap; de Kruif, John

    2007-01-01

    Seasonal epidemics of West Nile virus (WNV) infection now occur throughout North America, causing clinical symptoms ranging from fever to encephalitis. There are no specific treatment options or licensed vaccines. Several classically developed vaccine candidates are being evaluated in clinical

  9. A potential disruptive technology in vaccine development: gene-based vaccines and their application to infectious diseases.

    Science.gov (United States)

    Kaslow, David C

    2004-10-01

    Vaccine development requires an amalgamation of disparate disciplines and has unique economic and regulatory drivers. Non-viral gene-based delivery systems, such as formulated plasmid DNA, are new and potentially disruptive technologies capable of providing 'cheaper, simpler, and more convenient-to-use' vaccines. Typically and somewhat ironically, disruptive technologies have poorer product performance, at least in the near-term, compared with the existing conventional technologies. Because successful product development requires that the product's performance must meet or exceed the efficacy threshold for a desired application, the appropriate selection of the initial product applications for a disruptive technology is critical for its successful evolution. In this regard, the near-term successes of gene-based vaccines will likely be for protection against bacterial toxins and acute viral and bacterial infections. Recent breakthroughs, however, herald increasing rather than languishing performance improvements in the efficacy of gene-based vaccines. Whether gene-based vaccines ultimately succeed in eliciting protective immunity in humans to persistent intracellular pathogens, such as HIV, malaria and tuberculosis, for which the conventional vaccine technologies have failed, remains to be determined. A success against any one of the persistent intracellular pathogens would be sufficient proof that gene-based vaccines represent a disruptive technology against which future vaccine technologies will be measured.

  10. Business models and opportunities for cancer vaccine developers.

    Science.gov (United States)

    Kudrin, Alex

    2012-10-01

    Despite of growing oncology pipeline, cancer vaccines contribute only to a minor share of total oncology-attributed revenues. This is mainly because of a limited number of approved products and limited sales from products approved under compassionate or via early access entry in smaller and less developed markets. However revenue contribution from these products is extremely limited and it remains to be established whether developers are breaking even or achieving profitability with existing sales. Cancer vaccine field is well recognized for high development costs and risks, low historical rates of investment return and high probability of failures arising in ventures, partnerships and alliances. The cost of reimbursement for new oncology agents is not universally acceptable to payers limiting the potential for a global expansion, market access and reducing probability of commercial success. In addition, the innovation in cancer immunotherapy is currently focused in small and mid-size biotech companies and academic institutions struggling for investment. Existing R&D innovation models are deemed unsustainable in current "value-for-money" oriented healthcare environment. New business models should be much more open to collaborative, networked and federated styles, which could help to outreach global, markets and increase cost-efficiencies across an entire value chain. Lessons learned from some developing countries and especially from South Korea illustrate that further growth of cancer vaccine industry will depends not only on new business models but also will heavily rely on regional support and initiatives from different bodies, such as governments, payers and regulatory bodies.

  11. Development of malaria vaccines that block transmission of parasites by mosquito vectors

    OpenAIRE

    Hisaeda, Hajime; Yasutomo, Koji

    2002-01-01

    Malaria is still one of the infectious diseases urgently requiring control and causes socioeconomic burdens on people residing in developing countries. Malaria vaccines are expected to control the disease. However, there is no effective vaccine available despite the intense efforts of malaria scientists. One strategy for a malaria vaccine is to prevent parasite spread by means of interfering with parasite development in mosquito vectors, which is the so-called transmission-blocking vaccine (T...

  12. Recent developments in nanocarrier-aided mucosal vaccination.

    Science.gov (United States)

    Kammona, Olga; Bourganis, Vassilis; Karamanidou, Theodora; Kiparissides, Costas

    2017-05-01

    To date, most of the licensed vaccines for mucosal delivery are based on live-attenuated viruses which carry the risk of regaining their pathogenicity. Therefore, the development of efficient nonviral vectors allowing the induction of potent humoral and cell-mediated immunity is regarded as an imperative scientific challenge as well as a commercial breakthrough for the pharma industries. For a successful translation to the clinic, such nanocarriers should protect the antigens from mucosal enzymes, facilitate antigen uptake by microfold cells and allow the copresentation of robust, safe for human use, mucosal adjuvants to antigen-presenting cells. Finally, the developed formulations should exhibit accuracy regarding the administered dose, a major drawback of mucosal vaccines in comparison with parenteral ones.

  13. Comparative Pathogenesis and Systems Biology for Biodefense Virus Vaccine Development

    Directory of Open Access Journals (Sweden)

    Gavin C. Bowick

    2010-01-01

    Full Text Available Developing vaccines to biothreat agents presents a number of challenges for discovery, preclinical development, and licensure. The need for high containment to work with live agents limits the amount and types of research that can be done using complete pathogens, and small markets reduce potential returns for industry. However, a number of tools, from comparative pathogenesis of viral strains at the molecular level to novel computational approaches, are being used to understand the basis of viral attenuation and characterize protective immune responses. As the amount of basic molecular knowledge grows, we will be able to take advantage of these tools not only to rationally attenuate virus strains for candidate vaccines, but also to assess immunogenicity and safety in silico. This review discusses how a basic understanding of pathogenesis, allied with systems biology and machine learning methods, can impact biodefense vaccinology.

  14. Malaria vaccine research and development: the role of the WHO MALVAC committee

    Science.gov (United States)

    2013-01-01

    The WHO Malaria Vaccine Advisory Committee (MALVAC) provides advice to WHO on strategic priorities, activities and technical issues related to global efforts to develop vaccines against malaria. MALVAC convened a series of meetings to obtain expert, impartial consensus views on the priorities and best practice for vaccine-related research and development strategies. The technical areas covered during these consultations included: guidance on clinical trial design for candidate sporozoite and asexual blood stage vaccines; measures of efficacy of malaria vaccines in Phase IIb and Phase III trials; standardization of immunoassays; the challenges of developing assays and designing trials for interventions against malaria transmission; modelling impact of anti-malarial interventions; whole organism malaria vaccines, and Plasmodium vivax vaccine-related research and evaluation. These informed discussions and opinions are summarized here to provide guidance on harmonization of strategies to help ensure high standards of practice and comparability between centres and the outcome of vaccine trials. PMID:24112689

  15. Transmission blocking malaria vaccines: Assays and candidates in clinical development.

    Science.gov (United States)

    Sauerwein, R W; Bousema, T

    2015-12-22

    Stimulated by recent advances in malaria control and increased funding, the elimination of malaria is now considered to be an attainable goal for an increasing number of malaria-endemic regions. This has boosted the interest in transmission-reducing interventions including vaccines that target sexual, sporogenic, and/or mosquito-stage antigens to interrupt malaria transmission (SSM-VIMT). SSM-VIMT aim to prevent human malaria infection in vaccinated communities by inhibiting parasite development within the mosquito after a blood meal taken from a gametocyte carrier. Only a handful of target antigens are in clinical development and progress has been slow over the years. Major stumbling blocks include (i) the expression of appropriately folded target proteins and their downstream purification, (ii) insufficient induction of sustained functional blocking antibody titers by candidate vaccines in humans, and (iii) validation of a number of (bio)-assays as correlate for blocking activity in the field. Here we discuss clinical manufacturing and testing of current SSM-VIMT candidates and the latest bio-assay development for clinical evaluation. New testing strategies are discussed that may accelerate the evaluation and application of SSM-VIMT. Copyright © 2015. Published by Elsevier Ltd.

  16. Controlled human infection models for vaccine development: Zika virus debate.

    Science.gov (United States)

    Gopichandran, Vijayaprasad

    2017-10-31

    An ethics panel, convened by the National Institute of Health and other research bodies in the USA, disallowed researchers from the Johns Hopkins University and University of Vermont from performing controlled human infection of healthy volunteers to develop a vaccine against Zika virus infection. The members published their ethical analysis and recommendations in February 2017. They have elaborated on the risks posed by human challenge with Zika virus to the volunteers and other uninvolved third parties and have systematically analysed the social value of such a human challenge experiment. They have also posited some mandatory ethical requirements which should be met before allowing the infection of healthy volunteers with the Zika virus. This commentary elaborates on the debate on the ethics of the human challenge model for the development of a Zika virus vaccine and the role of systematic ethical analysis in protecting the interests of research participants. It further analyses the importance of this debate to the development of a Zika vaccine in India.

  17. Vaccinations

    Science.gov (United States)

    ... disease — reinforcing the importance of vaccines in your pet's preventive health care program. Are there risks? Any treatment carries some risk, but these risks should be weighed against the benefits of protecting your pet from potentially fatal diseases. ...

  18. Vaccine hesitancy

    Science.gov (United States)

    Dubé, Eve; Laberge, Caroline; Guay, Maryse; Bramadat, Paul; Roy, Réal; Bettinger, Julie A.

    2013-01-01

    Despite being recognized as one of the most successful public health measures, vaccination is perceived as unsafe and unnecessary by a growing number of individuals. Lack of confidence in vaccines is now considered a threat to the success of vaccination programs. Vaccine hesitancy is believed to be responsible for decreasing vaccine coverage and an increasing risk of vaccine-preventable disease outbreaks and epidemics. This review provides an overview of the phenomenon of vaccine hesitancy. First, we will characterize vaccine hesitancy and suggest the possible causes of the apparent increase in vaccine hesitancy in the developed world. Then we will look at determinants of individual decision-making about vaccination. PMID:23584253

  19. Intellectual property rights and challenges for development of affordable human papillomavirus, rotavirus and pneumococcal vaccines: Patent landscaping and perspectives of developing country vaccine manufacturers.

    Science.gov (United States)

    Chandrasekharan, Subhashini; Amin, Tahir; Kim, Joyce; Furrer, Eliane; Matterson, Anna-Carin; Schwalbe, Nina; Nguyen, Aurélia

    2015-11-17

    The success of Gavi, the Vaccine Alliance depends on the vaccine markets providing appropriate, affordable vaccines at sufficient and reliable quantities. Gavi's current supplier base for new and underutilized vaccines, such as the human papillomavirus (HPV), rotavirus, and the pneumococcal conjugate vaccine is very small. There is growing concern that following globalization of laws on intellectual property rights (IPRs) through trade agreements, IPRs are impeding new manufacturers from entering the market with competing vaccines. This article examines the extent to which IPRs, specifically patents, can create such obstacles, in particular for developing country vaccine manufacturers (DCVMs). Through building patent landscapes in Brazil, China, and India and interviews with manufacturers and experts in the field, we found intense patenting activity for the HPV and pneumococcal vaccines that could potentially delay the entry of new manufacturers. Increased transparency around patenting of vaccine technologies, stricter patentability criteria suited for local development needs and strengthening of IPRs management capabilities where relevant, may help reduce impediments to market entry for new manufacturers and ensure a competitive supplier base for quality vaccines at sustainably low prices. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  20. Recent developments in mucosal vaccines against prion diseases.

    Science.gov (United States)

    Sakaguchi, Suehiro; Arakawa, Takeshi

    2007-02-01

    Bovine spongiform encephalopathy in cattle is highly suspected to be orally transmitted to humans through contaminated food, causing new variant Creutzfeldt-Jakob disease. However, no prophylactic procedures against these diseases, such as vaccines, in particular those stimulating mucosal protective immunity, have been established. The causative agents of these diseases, termed prions, consist of the host-encoded prion protein (PrP). Therefore, prions are immunologically tolerated, inducing no host antibody responses. This immune tolerance to PrP has hampered the development of vaccines against prions. We and others recently reported that the immune tolerance could be successfully broken and mucosal immunity could be stimulated by mucosal immunization of mice with PrP fused with bacterial enterotoxin or delivered using an attenuated Salmonella strain, eliciting significantly higher immunoglobulin A and G antibody responses against PrP. In this review, we will discuss these reports.

  1. New live mycobacterial vaccines: the Geneva consensus on essential steps towards clinical development

    NARCIS (Netherlands)

    Kamath, A.T.; Fruth, U.; Brennan, M.; Dobbelaer, R.; Hubrechts, P.; Ho, M.M.; Mayner, R.E.; Thole, J.E.R.; Walker, K.B.; Liu, C.M.; Lambert, P.H.

    2005-01-01

    As the disease caused by Mycobacterium tuberculosis continues to be a burden, which the world continues to suffer, there is a concerted effort to find new vaccines to combat this problem. Of the various vaccines strategies, one viable option is the development of live mycobacterial vaccines. A

  2. Development and evaluation of a potential universal Salmonella-vectored avian influenza vaccine

    Science.gov (United States)

    Development of vaccines for effective control of avian influenza (AI) virus in poultry and wild birds is in high demand. Most AI vaccines target the immunodominant antigens such as hemagglutinin (HA) and neuraminidase (NA); however, these vaccines only provide protection against a particular AI ser...

  3. Humoral Immunity to Primary Smallpox Vaccination: Impact of Childhood versus Adult Immunization on Vaccinia Vector Vaccine Development in Military Populations.

    Directory of Open Access Journals (Sweden)

    Bonnie M Slike

    Full Text Available Modified Vaccinia virus has been shown to be a safe and immunogenic vector platform for delivery of HIV vaccines. Use of this vector is of particular importance to the military, with the implementation of a large scale smallpox vaccination campaign in 2002 in active duty and key civilian personnel in response to potential bioterrorist activities. Humoral immunity to smallpox vaccination was previously shown to be long lasting (up to 75 years and protective. However, using vaccinia-vectored vaccine delivery for other diseases on a background of anti-vector antibodies (i.e. pre-existing immunity may limit their use as a vaccine platform, especially in the military. In this pilot study, we examined the durability of vaccinia antibody responses in adult primary vaccinees in a healthy military population using a standard ELISA assay and a novel dendritic cell neutralization assay. We found binding and neutralizing antibody (NAb responses to vaccinia waned after 5-10 years in a group of 475 active duty military, born after 1972, who were vaccinated as adults with Dryvax®. These responses decreased from a geometric mean titer (GMT of 250 to baseline (30 years with a GMT of 210 (range 112-3234. This data suggests limited durability of antibody responses in adult vaccinees compared to those vaccinated in childhood and further that adult vaccinia recipients may benefit similarly from receipt of a vaccinia based vaccine as those who are vaccinia naïve. Our findings may have implications for the smallpox vaccination schedule and support the ongoing development of this promising viral vector in a military vaccination program.

  4. Deinococcus Mn2+ -Peptide Complex: A Novel Approach to Alphavirus Vaccine Development

    Science.gov (United States)

    2016-08-05

    results suggest that this approach can easily be extended to any pathogen of interest. Introduction The discovery and commercial development of a...household products. An irradiated-cryopreserved malaria vaccine, PfSPZ, is also currently under clinical trials [13]. Yet, the long-standing tenet of...sporozoite malaria vaccine. Vaccine. 2009;27(27):3675-80. Epub 2008/12/17. doi: 10.1016/j.vaccine.2008.11.073. PubMed PMID: 19071177. 9. Carpenter CM

  5. [Travelers' vaccines].

    Science.gov (United States)

    Ouchi, Kazunobu

    2011-09-01

    The number of Japanese oversea travelers has gradually increased year by year, however they usually pay less attention to the poor physical condition at the voyage place. Many oversea travelers caught vaccine preventable diseases in developing countries. The Vaccine Guideline for Oversea Travelers 2010 published by Japanese Society of Travel Health will be helpful for spreading the knowledge of travelers' vaccine and vaccine preventable diseases in developing countries. Many travelers' vaccines have not licensed in Japan. I hope these travelers' vaccines, such as typhoid vaccine, meningococcal vaccine, cholera vaccine and so on will be licensed in the near future.

  6. Manufacturing costs of HPV vaccines for developing countries.

    Science.gov (United States)

    Clendinen, Chaevia; Zhang, Yapei; Warburton, Rebecca N; Light, Donald W

    2016-11-21

    Nearly all of the 500,000 new cases of cervical cancer and 270,000 deaths occur in middle or lower income countries. Yet the two most prevalent HPV vaccines are unaffordable to most. Even prices to Gavi, the Vaccine Alliance, are unaffordable to graduating countries, once they lose Gavi subsidies. Merck and Glaxosmithkline (GSK) claim their prices to Gavi equal their manufacturing costs; but these costs remain undisclosed. We undertook this investigation to estimate those costs. Searches in published and commercial literature for information about the manufacturing of these vaccines. Interviews with experts in vaccine manufacturing. This detailed sensitivity analysis, based on the best available evidence, finds that after a first set of batches for affluent markets, manufacturing costs of Gardasil for developing countries range between $0.48 and $0.59 a dose, a fraction of its alleged costs of $4.50. Because volume of Cervarix is low, its per unit costs are much higher, though at comparable volumes, its costs would be similar. Given the recovery of fixed and annual costs from sales in affluent markets, Merck's break-even price to Gavi could be $0.50-$0.60, not $4.50. These savings could support Gavi programs to strengthen delivery and increase coverage. Outside Gavi, prices to lower- and middle-income countries, with profit, could also be lowered and made available to millions more adolescents at risk. These estimates and their policy implications deserve further discussion. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  7. Human-animal chimeras for vaccine development: an endangered species or opportunity for the developing world?

    Directory of Open Access Journals (Sweden)

    Daar Abdallah S

    2010-05-01

    Full Text Available Abstract Background In recent years, the field of vaccines for diseases such as Human Immunodeficiency Virus (HIV which take a heavy toll in developing countries has faced major failures. This has led to a call for more basic science research, and development as well as evaluation of new vaccine candidates. Human-animal chimeras, developed with a 'humanized' immune system could be useful to study infectious diseases, including many neglected diseases. These would also serve as an important tool for the efficient testing of new vaccine candidates to streamline promising candidates for further trials in humans. However, developing human-animal chimeras has proved to be controversial. Discussion Development of human-animal chimeras for vaccine development has been slowed down because of opposition by some philosophers, ethicists and policy makers in the west-they question the moral status of such animals, and also express discomfort about transgression of species barriers. Such opposition often uses a contemporary western world view as a reference point. Human-animal chimeras are often being created for diseases which cause significantly higher morbidity and mortality in the developing world as compared to the developed world. We argue in our commentary that given this high disease burden, we should look at socio-cultural perspectives on human-animal chimera like beings in the developing world. On examination, it's clear that such beings have been part of mythology and cultural descriptions in many countries in the developing world. Summary To ensure that important research on diseases afflicting millions like malaria, HIV, Hepatitis-C and dengue continues to progress, we recommend supporting human-animal chimera research for vaccine development in developing countries (especially China and India which have growing technical expertise in the area. The negative perceptions in some parts of the west about human-animal chimeras can be used as an

  8. Human-animal chimeras for vaccine development: an endangered species or opportunity for the developing world?

    Science.gov (United States)

    Bhan, Anant; Singer, Peter A; Daar, Abdallah S

    2010-05-19

    In recent years, the field of vaccines for diseases such as Human Immunodeficiency Virus (HIV) which take a heavy toll in developing countries has faced major failures. This has led to a call for more basic science research, and development as well as evaluation of new vaccine candidates. Human-animal chimeras, developed with a 'humanized' immune system could be useful to study infectious diseases, including many neglected diseases. These would also serve as an important tool for the efficient testing of new vaccine candidates to streamline promising candidates for further trials in humans. However, developing human-animal chimeras has proved to be controversial. Development of human-animal chimeras for vaccine development has been slowed down because of opposition by some philosophers, ethicists and policy makers in the west-they question the moral status of such animals, and also express discomfort about transgression of species barriers. Such opposition often uses a contemporary western world view as a reference point. Human-animal chimeras are often being created for diseases which cause significantly higher morbidity and mortality in the developing world as compared to the developed world. We argue in our commentary that given this high disease burden, we should look at socio-cultural perspectives on human-animal chimera like beings in the developing world. On examination, it's clear that such beings have been part of mythology and cultural descriptions in many countries in the developing world. To ensure that important research on diseases afflicting millions like malaria, HIV, Hepatitis-C and dengue continues to progress, we recommend supporting human-animal chimera research for vaccine development in developing countries (especially China and India which have growing technical expertise in the area). The negative perceptions in some parts of the west about human-animal chimeras can be used as an opportunity for nurturing important vaccine development

  9. Oral Vaccine Development by Molecular Display Methods Using Microbial Cells.

    Science.gov (United States)

    Shibasaki, Seiji; Ueda, Mitsuyoshi

    2016-01-01

    Oral vaccines are easier to administer than injectable vaccines. To induce an adequate immune response using vaccines, antigenic proteins are usually combined with adjuvant materials. This chapter presents methodologies for the design of oral vaccines using molecular display technology. In molecular display technology, antigenic proteins are displayed on a microbial cell surface with adjuvant ability. This technology would provide a quite convenient process to produce oral vaccines when the DNA sequence of an efficient antigenic protein is available. As an example, oral vaccines against candidiasis were introduced using two different molecular display systems with Saccharomyces cerevisiae and Lactobacillus casei.

  10. Immunogenicity of HPV prophylactic vaccines: Serology assays and their use in HPV vaccine evaluation and development.

    Science.gov (United States)

    Pinto, Ligia A; Dillner, Joakim; Beddows, Simon; Unger, Elizabeth R

    2018-01-17

    When administered as standard three-dose schedules, the licensed HPV prophylactic vaccines have demonstrated extraordinary immunogenicity and efficacy. We summarize the immunogenicity of these licensed vaccines and the most commonly used serology assays, with a focus on key considerations for one-dose vaccine schedules. Although immune correlates of protection against infection are not entirely clear, both preclinical and clinical evidence point to neutralizing antibodies as the principal mechanism of protection. Thus, immunogenicity assessments in vaccine trials have focused on measurements of antibody responses to the vaccine. Non-inferiority of antibody responses after two doses of HPV vaccines separated by 6 months has been demonstrated and this evidence supported the recent WHO recommendations for two-dose vaccination schedules in both boys and girls 9-14 years of age. There is also some evidence suggesting that one dose of HPV vaccines may provide protection similar to the currently recommended two-dose regimens but robust data on efficacy and immunogenicity of one-dose vaccine schedules are lacking. In addition, immunogenicity has been assessed and reported using different methods, precluding direct comparison of results between different studies and vaccines. New head-to-head vaccine trials evaluating one-dose immunogenicity and efficacy have been initiated and an increase in the number of trials relying on immunobridging is anticipated. Therefore, standardized measurement and reporting of immunogenicity for the up to nine HPV types targeted by the current vaccines is now critical. Building on previous HPV serology assay standardization and harmonization efforts initiated by the WHO HPV LabNet in 2006, new secondary standards, critical reference reagents and testing guidelines will be generated as part of a new partnership to facilitate harmonization of the immunogenicity testing in new HPV vaccine trials. Copyright © 2018 Elsevier Ltd. All rights

  11. Developing Universal Influenza Vaccines: Hitting the Nail, Not Just on the Head

    Directory of Open Access Journals (Sweden)

    Lidewij C. M. Wiersma

    2015-03-01

    Full Text Available Influenza viruses have a huge impact on public health. Current influenza vaccines need to be updated annually and protect poorly against antigenic drift variants or novel emerging subtypes. Vaccination against influenza can be improved in two important ways, either by inducing more broadly protective immune responses or by decreasing the time of vaccine production, which is relevant especially during a pandemic outbreak. In this review, we outline the current efforts to develop so-called “universal influenza vaccines”, describing antigens that may induce broadly protective immunity and novel vaccine production platforms that facilitate timely availability of vaccines.

  12. Developing Universal Influenza Vaccines: Hitting the Nail, Not Just on the Head

    Science.gov (United States)

    Wiersma, Lidewij C. M.; Rimmelzwaan, Guus F.; de Vries, Rory D.

    2015-01-01

    Influenza viruses have a huge impact on public health. Current influenza vaccines need to be updated annually and protect poorly against antigenic drift variants or novel emerging subtypes. Vaccination against influenza can be improved in two important ways, either by inducing more broadly protective immune responses or by decreasing the time of vaccine production, which is relevant especially during a pandemic outbreak. In this review, we outline the current efforts to develop so-called “universal influenza vaccines”, describing antigens that may induce broadly protective immunity and novel vaccine production platforms that facilitate timely availability of vaccines. PMID:26343187

  13. Development of antifertility vaccine using sperm specific proteins

    Directory of Open Access Journals (Sweden)

    A H Bandivdekar

    2014-01-01

    Full Text Available Sperm proteins are known to be associated with normal fertilization as auto- or iso-antibodies to these proteins may cause infertility. Therefore, sperm proteins have been considered to be the potential candidate for the development of antifertility vaccine. Some of the sperm proteins proved to be promising antigens for contraceptive vaccine includes lactate dehydrogenase (LDH-C4, protein hyaluronidase (PH-20, and Eppin. Immunization with LDH-C4 reduced fertility in female baboons but not in female cynomolgus macaques. Active immunization with PH-20 resulted in 100 per cent inhibition of fertility in male guinea pigs but it induced autoimmune orchitis. Immunization with Eppin elicited high antibody titres in 78 per cent of immunized monkeys and induced infertility but the immunopathological effect of immunization was not examined. Human sperm antigen (80kDa HSA is a sperm specific, highly immunogenic and conserved sperm protein. Active immunization with 80kDa HSA induced immunological infertility in male and female rats. Partial N-terminal amino acid sequence of 80kDa HSA (Peptide NT and its peptides (Peptides 1, 2, 3 and 4 obtained by enzymatic digestion did not show homology with any of the known proteins in gene bank. Peptides NT, 1, 2 and 4 were found to mimic immunobiological activity of native protein. Passive administration of antibodies to peptides NT, 1, 2 and 4 induced infertility in male and female rats and peptide 1 was found to be most effective in suppressing fertility. Active immunization with keyhole limpet haemocynin (KLH conjugated synthetic peptide 1 impaired fertility in all the male rabbits and six of the seven male marmosets. The fertility was restored following decline in antibody titre. All these findings on 80kDA HAS suggest that the synthetic Peptide-1 of 80kDa HSA is the promising candidate for development of male contraceptive vaccine.

  14. Development of stable influenza vaccine powder formulations : Challenges and possibilities

    NARCIS (Netherlands)

    Amorij, J-P; Huckriede, A; Wilschut, J; Frijlink, H W; Hinrichs, W L J

    2008-01-01

    Influenza vaccination represents the cornerstone of influenza prevention. However, today all influenza vaccines are formulated as liquids that are unstable at ambient temperatures and have to be stored and distributed under refrigeration. In order to stabilize influenza vaccines, they can be brought

  15. Advances in development and evaluation of bovine herpesvirus 1 vaccines

    NARCIS (Netherlands)

    Oirschot, van J.T.; Kaashoek, M.J.; Rijsewijk, F.A.M.

    1996-01-01

    This review deals with conventional and modern bovine herpesvirus 1 (BHV1) vaccines. Conventional vaccines are widely used to prevent clinical signs of infectious bovine rhinotracheitis. The use of conventional vaccines, however, does not appear to have resulted in reduction of the prevalence of

  16. Development of cross-protective influenza A vaccines based on cellular responses

    Directory of Open Access Journals (Sweden)

    Peter Christiaan Soema

    2015-05-01

    Full Text Available Seasonal influenza vaccines provide protection against matching influenza A virus (IAV strains mainly through the induction of neutralizing serum IgG antibodies. However, these antibodies fail to confer a protective effect against mismatched IAV. This lack of efficacy against heterologous influenza strains has spurred the vaccine development community to look for other influenza vaccine concepts, which have the ability to elicit cross-protective immune responses.One of the concepts that is currently been worked on are influenza vaccines inducing influenza-specific T cell responses. T cells are able to lyse infected host cells, thereby clearing the virus. More interestingly, these T cells can recognize highly conserved epitopes of internal influenza proteins, making cellular responses less vulnerable to antigenic variability. T cells are therefore cross-reactive against many influenza strains, and thus are a promising concept for future influenza vaccines. Despite their potential, there are currently no T cell based IAV vaccines on the market. Selection of the proper antigen, appropriate vaccine formulation and evaluation of the efficacy of T cell vaccines remains challenging, both in preclinical and clinical settings.In this review, we will discuss the current developments in influenza T cell vaccines, focusing on existing protein-based and novel peptide-based vaccine formulations. Furthermore, we will discuss the feasibility of influenza T cell vaccines and their possible use in the future.

  17. Investing in vaccines for developing countries: How public-private partnerships can confront neglected diseases.

    Science.gov (United States)

    Yaïch, Mansour

    2009-06-01

    This commentary discusses the barrier of vaccine price on sustainable immunization programs in developing countries and offers examples of new mechanisms driven by public-private partnerships to overcome issues of affordability. These mechanisms include Advance Market Commitments with vaccine manufacturers, which take a demand-pull approach to ensure increased production of available vaccines or development of new vaccines for neglected diseases. A second approach applies a supply-push mechanism, such as technology transfer to developing-country manufacturers. A public-private partnership that set long-term, maximum public-sector pricing to increase access of a Japanese encephalitis vaccine for the developing world is highlighted. Lessons learned from this experience can be applied to address common obstacles to new vaccine introduction in resource-limited countries, including issues of affordability, manufacturing capacity, equity in access and quality assurance.

  18. Approaches to tuberculosis mucosal vaccine development using nanoparticles and microparticles: a review.

    Science.gov (United States)

    Caetano, Liliana Aranha; Almeida, António José; Gonćalves, Lídia Maria Diogo

    2014-09-01

    Next-generation vaccines for tuberculosis should be designed to prevent the infection and to achieve sterile eradication of Mycobacterium tuberculosis. Mucosal vaccination is a needle-free vaccine strategy that provides protective immunity against pathogenic bacteria and viruses in both mucosal and systemic compartments, being a promising alternative to current tuberculosis vaccines. Micro and nanoparticles have shown great potential as delivery systems for mucosal vaccines. In this review, the immunological principles underlying mucosal vaccine development will be discussed, and the application of mucosal adjuvants and delivery systems to the enhancement of protective immune responses at mucosal surfaces will be reviewed, in particular those envisioned for oral and nasal routes of administration. An overview of the essential vaccine candidates for tuberculosis in clinical trials will be provided, with special emphasis on the potential different antigens and immunization regimens.

  19. Bacterial superglue enables easy development of efficient virus-like particle based vaccines

    DEFF Research Database (Denmark)

    Thrane, Susan; Janitzek, Christoph M; Matondo, Sungwa

    2016-01-01

    BACKGROUND: Virus-like particles (VLPs) represent a significant advance in the development of subunit vaccines, combining high safety and efficacy. Their particulate nature and dense repetitive subunit organization makes them ideal scaffolds for display of vaccine antigens. Traditional approaches...... vaccine antigens fused to SpyCatcher or SpyTag resulted in formation of antigen-VLP complexes with coupling efficiencies (% occupancy of total VLP binding sites) ranging from 22-88 %. In mice, spy-VLP vaccines presenting the malaria proteins Pfs25 or VAR2CSA markedly increased antibody titer, affinity......, longevity and functional efficacy compared to corresponding vaccines employing monomeric proteins. The spy-VLP vaccines also effectively broke B cell self-tolerance and induced potent and durable antibody responses upon vaccination with cancer or allergy-associated self-antigens (PD-L1, CTLA-4 and IL-5...

  20. Reaching more children with vaccines in developing countries: key challenges of innovation and delivery.

    Science.gov (United States)

    Popova, Olga; Ibarra de Palacios, Patricia

    2016-01-01

    As we reach the deadline for the United Nations fourth Millennium Development Goal to reduce child mortality, many inequalities in vaccine access still exist, particularly for children in developing countries. Here we discuss some of the barriers to vaccine access in these countries, as well as some of the innovative approaches that could address these. Finally, we discuss the need to create a global environment conducive to innovation directed at low-resource settings, aimed to ultimately increase vaccine coverage.

  1. Socioeconomic differences in childhood vaccination in developed countries: a systematic review of quantitative studies.

    Science.gov (United States)

    Bocquier, Aurélie; Ward, Jeremy; Raude, Jocelyn; Peretti-Watel, Patrick; Verger, Pierre

    2017-11-01

    The reasons for vaccine hesitancy and its relation to individual socioeconomic status (SES) must be better understood. Areas covered: This review focused on developed countries with programs addressing major financial barriers to vaccination access. We systematically reviewed differences by SES in uptake of publicly funded childhood vaccines and in cognitive determinants (beliefs, attitudes) of parental decisions about vaccinating their children. Using the PRISMA statement to guide this review, we searched three electronic databases from January 2000 through April 2016. We retained 43 articles; 34 analyzed SES differences in childhood vaccine uptake, 7 examined differences in its cognitive determinants, and 2 both outcomes. Expert commentary: Results suggest that barriers to vaccination access persist among low-SES children in several settings. Vaccination programs could be improved to provide all mandatory and recommended vaccines 100% free of charge, in both public organizations and private practices, and to reimburse vaccine administration. Multicomponent interventions adapted to the context could also be effective in reducing these inequalities. For specific vaccines (notably for measles, mumps, and rubella), in UK and Germany, uptake was lowest among the most affluent. Interventions carefully tailored to respond to specific concerns of vaccine-hesitant parents, without reinforcing hesitancy, are needed.

  2. Development of a SARS Coronavirus Vaccine from Recombinant Spike Protein Plus Delta Inulin Adjuvant.

    Science.gov (United States)

    McPherson, Clifton; Chubet, Richard; Holtz, Kathy; Honda-Okubo, Yoshikazu; Barnard, Dale; Cox, Manon; Petrovsky, Nikolai

    2016-01-01

    Given periodic outbreaks of fatal human infections caused by coronaviruses, development of an optimal coronavirus vaccine platform capable of rapid production is an ongoing priority. This chapter describes the use of an insect cell expression system for rapid production of a recombinant vaccine against severe acute respiratory syndrome coronavirus (SARS). Detailed methods are presented for expression, purification, and release testing of SARS recombinant spike protein antigen, followed by adjuvant formulation and animal testing. The methods herein described for rapid development of a highly protective SARS vaccine are equally suited to rapid development of vaccines against other fatal human coronavirus infections, e.g., the MERS coronavirus.

  3. Development of vaccines against Plasmodium falciparum malaria: taking lessons from naturally acquired protective immunity

    DEFF Research Database (Denmark)

    Hviid, Lars

    2007-01-01

    The acquisition of substantial anti-malarial protection in people naturally exposed to P. falciparum is often cited as evidence that malaria vaccines can be developed, but is rarely used to guide the development. We are pursuing the development of vaccines based on antigens and immune responses...

  4. Upregulation of TGF-beta 1 in neonates of mothers receiving Influenza A (H1N1) vaccination during pregnancy

    DEFF Research Database (Denmark)

    Bischoff, Anne Louise; Folsgaard, N.; Bisgaard, H.

    2012-01-01

    Background: Influenza vaccination of pregnant women is generally considered safe,but the effects on the immune system of the unborn child are unknown.Objectives: Our primary objective was to explore differences in cytokine and chemokine levels in nasal mucosal lining fluid in neonates of mothers....... aureus; older siblings; furred animals in home; smoking during 3rd trimester; and mothers’ atopic disease. Conclusion: These findings suggest that Influenza A (H1N1) vaccination during pregnancy affects the mucosal immune competence of the unborn child. The up-regulation of TGF-b1 and down...... vaccinated during or after pregnancy. Method: IFN-c, IL-1b, IL-2, -4, -5, -10, - 12p70, -13, -17, TNF-a, IL-8, eotaxin-1,eotaxin-3, IP-10, MCP-1, MCP-4, MDC, MIP-1b, TGF-b1 and TARC were quantified in nasal mucosal lining fluid in neonates of mothers receiving Influenza A (H1N1v) vaccine during (n = 52...

  5. Quality vaccines for all people: Report on the 16th annual general meeting of the Developing Countries Vaccine Manufacturers' Network, 05-07th October 2015, Bangkok, Thailand.

    Science.gov (United States)

    Pagliusi, Sonia; Ting, Ching-Chia; Khomvilai, Sumana

    2016-06-30

    The Developing Countries Vaccine Manufacturers Network (DCVMN) assembled high-profile leaders from global health organisations and vaccine manufactures for its 16th Annual General Meeting to work towards a common goal: providing quality vaccines for all people. Vaccines contribute to a healthy community and robust health system; the Ebola outbreak has raised awareness of the threat and damage one single infectious disease can make, and it is clear that the world was not prepared. However, more research to better understand emerging infectious agents might lead to suitable vaccines which help prevent future outbreaks. DCVMN members presented their progress in developing novel vaccines against Dengue, HPV, Chikungunya, Cholera, cell-based influenza and other vaccines, demonstrating the commitment towards eliminating and eradicating preventable diseases worldwide through global collaboration and technology transfer. The successful introduction of novel Sabin-IPV and Oral Cholera vaccine in China and Korea respectively in 2015 was highlighted. In order to achieve global immunisation, local authorities and community leaders play an important role in the decision-making in vaccine introduction and uptake, based on the ability of vaccines to protect vaccinated people and protect non-vaccinated in the community through herd immunity. Reducing the risk of vaccine shortages can also be achieved by increasing regulatory convergence at regional and international levels. Combatting preventable diseases remains challenging, and collective efforts for improving multi-centre clinical trials, creating regional vaccine security strategies, fostering developing vaccine markets and procurement, and building trust in vaccines were discussed. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  6. Current views on the potential for development of a HIV vaccine.

    Science.gov (United States)

    Cohen, Kristen W; Frahm, Nicole

    2017-03-01

    Despite many recent advances in the HIV prevention landscape, an effective vaccine remains the most promising tool to end the HIV-1 pandemic. Areas covered: This review summarizes past HIV vaccine efficacy trials and current vaccine strategies as well as new approaches about to move into first-in-human trials. Expert opinion: Despite many setbacks in early HIV vaccine efficacy trials, the success of RV144 has provided the glimmer of hope necessary to invigorate the vaccine field, and has led to the development of a large number of vaccine strategies aiming at inducing an array of different immune responses. The follow-up pox-protein trials, developed to replicate and enhance the polyfunctional antibody responses induced by the RV144 regimen, are already reaching efficacy trials, while a large body of work providing a more complete understanding of the development of broadly neutralizing antibodies is now being translated into immunogen design using several different strategies. T-cell based vaccines, fallen out of favor after Ad5-based trials showed increased infection rates in Ad5 seropositive vaccine recipients, are experiencing a comeback based in part on the promising results from non-human primate challenge studies using rhCMV-based immunogens. This diverse array of vaccine candidates may finally allow us to identify a broadly effective HIV vaccine able to contain the epidemic.

  7. [Introduction of vaccination against human papillomavirus in developing countries: update and perspectives].

    Science.gov (United States)

    Hessel, L

    2009-08-01

    Cervical cancer and other diseases related to human papillomavirus (HPV) represent a global public health problem. Safe and effective vaccines are now available and already used in many industrialized countries. Immunization offers the best hope for protecting the population against a disease that is the second most deadly cancer in the developing world and the first most deadly in Africa. The World Health Organization currently recommends introduction of HVP vaccination in developing countries. Widespread vaccination could be beneficial in numerous domains other than primary prevention of cervical cancer. Efforts to overcome the numerous obstacles and speed up implementation of HVP vaccination programs are now underway in many areas ranging from related scientific issues such as epidemiology and clinical research to administrative concerns such as healthcare economics, vaccination guidelines, public acceptation, program funding, and universal access. Vaccine manufacturers have committed themselves to working in partnership with national and international organizations to ensure access to HPV vaccine for all countries regardless of economic level, Although numerous issues must be resolved to optimize the use of HPV vaccines and ensure synergistic integration of vaccination, screening and treatment, current initiatives and efforts should allow introduction of HPV vaccination in developing countries in a not too distant future.

  8. Development of Live-Attenuated Influenza Vaccines against Outbreaks of H5N1 Influenza

    Directory of Open Access Journals (Sweden)

    Yinglei Yi

    2012-12-01

    Full Text Available Several global outbreaks of highly pathogenic avian influenza (HPAI H5N1 virus have increased the urgency of developing effective and safe vaccines against H5N1. Compared with H5N1 inactivated vaccines used widely, H5N1 live-attenuated influenza vaccines (LAIVs have advantages in vaccine efficacy, dose-saving formula, long-lasting effect, ease of administration and some cross-protective immunity. Furthermore, H5N1 LAIVs induce both humoral and cellular immune responses, especially including improved IgA production at the mucosa. The current trend of H5N1 LAIVs development is toward cold-adapted, temperature-sensitive or replication-defective vaccines, and moreover, H5N1 LAIVs plus mucosal adjuvants are promising candidates. This review provides an update on the advantages and development of H5N1 live-attenuated influenza vaccines.

  9. Human papilloma virus vaccination for control of cervical cancer: a challenge for developing countries.

    Science.gov (United States)

    Bello, F A; Enabor, O O; Adewole, I F

    2011-03-01

    Primary HPV prevention may be the key to reducing incidence and burden of cervical cancer particularly in resource-poor countries. Vaccination programmes are already established in several developed regions, but several grey areas stand in the path of similar success in developing countries. This review sought to identify challenges of HPV vaccination in developing countries and discuss vaccine use, pitfalls and controversies; areas requiring collaborative efforts were identified. A Pub Med search was done; key words included Human papilloma virus, HPV vaccine and sub-Saharan Africa. Other resources included locally-published articles and additional internet resources. The potential benefit of mass HPV vaccination appears enormous. However, the challenges of competing health demands, poverty, ignorance, religion, culture, weak health system, establishment of an effective intersectoral collaboration and underfunding must be overcome to make maximal vaccine uptake a reality. Education and effective communication is crucial in achieving successful immunization programmes.

  10. The mucosal immune system: From dentistry to vaccine development.

    Science.gov (United States)

    Kiyono, Hiroshi; Azegami, Tatsuhiko

    2015-01-01

    The oral cavity is the beginning of the aero-digestive tract, which is covered by mucosal epithelium continuously under the threat of invasion of pathogens, it is thus protected by the mucosal immune system. In the early phase of our scientific efforts for the demonstration of mucosal immune system, dental science was one of major driving forces due to their foreseeability to use oral immunity for the control of oral diseases. The mucosal immune system is divided functionally into, but interconnected inductive and effector sites. Intestinal Peyer's patches (PPs) are an inductive site containing antigen-sampling M cells and immunocompetent cells required to initiate antigen-specific immune responses. At effector sites, PP-originated antigen-specific IgA B cells become plasma cells to produce polymeric IgA and form secretory IgA by binding to poly-Ig receptor expressed on epithelial cells for protective immunity. The development of new-generation mucosal vaccines, including the rice-based oral vaccine MucoRice, on the basis of the coordinated mucosal immune system is a promising strategy for the control of mucosal infectious diseases.

  11. Development of vaccines against Crimean-Congo haemorrhagic fever virus.

    Science.gov (United States)

    Dowall, Stuart D; Carroll, Miles W; Hewson, Roger

    2017-10-20

    Crimean-Congo haemorrhagic fever virus (CCHFV) is a deadly human pathogen of the utmost seriousness being highly lethal causing devastating disease symptoms that result in intense and prolonged suffering to those infected. During the past 40years, this virus has repeatedly caused sporadic outbreaks responsible for relatively low numbers of human casualties, but with an alarming fatality rate of up to 80% in clinically infected patients. CCHFV is transmitted to humans by Hyalomma ticks and contact with the blood of viremic livestock, additionally cases of human-to-human transmission are not uncommon in nosocomial settings. The incidence of CCHF closely matches the geographical range of permissive ticks, which are widespread throughout Africa, Asia, the Middle East and Europe. As such, CCHFV is the most widespread tick-borne virus on earth. It is a concern that recent data shows the geographic distribution of Hyalomma ticks is expanding. Migratory birds are also disseminating Hyalomma ticks into more northerly parts of Europe thus potentially exposing naïve human populations to CCHFV. The virus has been imported into the UK on two occasions in the last five years with the first fatal case being confirmed in 2012. A licensed vaccine to CCHF is not available. In this review, we discuss the background and complications surrounding this limitation and examine the current status and recent advances in the development of vaccines against CCHFV. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

  12. Development, Theoretical Framework, and Outcome Evaluation from Implementation of a Parent and Teacher-Delivered Adolescent Intervention on Adolescent Vaccination

    OpenAIRE

    Gargano, Lisa M; Herbert, Natasha L; Painter, Julia E.; Sales, Jessica M.; Vogt, Tara M.; Morfaw, Christopher; Jones, LaDawna M.; Murray4, Dennis; DiClemente, Ralph J.; Hughes, James M.

    2014-01-01

    The Advisory Committee on Immunization Practices recommended immunization schedule for adolescents includes three vaccines (Tdap, HPV, and MCV4) and annual influenza vaccination. Given the increasing number of recommended vaccines for adolescents and health and economic costs associated with non-vaccination, it is imperative that effective strategies for increasing vaccination rates among adolescents be developed. This article describes the development, theoretical framework, and initial firs...

  13. Mucosal vaccines: a paradigm shift in the development of mucosal adjuvants and delivery vehicles.

    Science.gov (United States)

    Srivastava, Atul; Gowda, Devegowda Vishakante; Madhunapantula, SubbaRao V; Shinde, Chetan G; Iyer, Meenakshi

    2015-04-01

    Mucosal immune responses are the first-line defensive mechanisms against a variety of infections. Therefore, immunizations of mucosal surfaces from which majority of infectious agents make their entry, helps to protect the body against infections. Hence, vaccinization of mucosal surfaces by using mucosal vaccines provides the basis for generating protective immunity both in the mucosal and systemic immune compartments. Mucosal vaccines offer several advantages over parenteral immunization. For example, (i) ease of administration; (ii) non-invasiveness; (iii) high-patient compliance; and (iv) suitability for mass vaccination. Despite these benefits, to date, only very few mucosal vaccines have been developed using whole microorganisms and approved for use in humans. This is due to various challenges associated with the development of an effective mucosal vaccine that can work against a variety of infections, and various problems concerned with the safe delivery of developed vaccine. For instance, protein antigen alone is not just sufficient enough for the optimal delivery of antigen(s) mucosally. Hence, efforts have been made to develop better prophylactic and therapeutic vaccines for improved mucosal Th1 and Th2 immune responses using an efficient and safe immunostimulatory molecule and novel delivery carriers. Therefore, in this review, we have made an attempt to cover the recent advancements in the development of adjuvants and delivery carriers for safe and effective mucosal vaccine production. © 2015 APMIS. Published by John Wiley & Sons Ltd.

  14. HPV induced cervical carcinogenesis: molecular basis and vaccine development.

    Science.gov (United States)

    Kaufmann, A M; Backsch, C; Schneider, A; Dürst, M

    2002-11-01

    Association of infection with papillomavirus and dysplasia of the cervix uteri has been firmly established. There are only few cervical cancers where no HPV DNA is detectable. The mechanism of epithelial cell immortalization by interaction with tumour suppressor genes p53 and pRb by viral oncogenes E6 and E7 is elucidated. Progression of the HPV infected cell to a malignant phenotype involves further modification of host gene expression and/or mutations. The appearance of chromosomal aberrations can lead to mutational inactivation or loss of tumour suppressor genes (TSG), activation and amplification of oncogenes, with importance for the process of carcinogenesis. Oncogene amplification, with exception of few reports, seems not to be a major mechanism in cervical carcinogenesis. In contrast, cytogenetic and loss of heterozygosity (LOH) results from CIN and invasive cancer demonstrate alterations at specific chromosomal regions, pointing at localisation of TSG. Genetic alterations at chromosomes 3p, 6p, 1lq were frequently found early in tumour development Primary invasive carcinoma showed additional allelic losses at chromosome arms 6q, 17p and 18q. Useful biological diagnostic and prognostic markers for high-risk HPV infection and malignant progression may be p16NK4 p27Kip, and NET-I/C4.8. Putative senescence genes relevant for HPV-induced carcinogenesis are localized on chromosomes 2, 4 and 10. Genes for Telomerase suppression are presumably located on chromosomes 3, 4 and 6. Natural immune responses to HPV infection exist Therefore, immune therapy is an attractive possibility for prevention and therapy of HPV infection. To date, vaccine development has reached clinical evaluation. Prophylaxis aims at the induction of virus neutralizing antibodies to capsid proteins. Virus-like particle vaccines are currently tested in clinical trials. Due to the long lag period between infection and clinical manifestation trials will take a long time until conclusive results are

  15. Nanoparticle based tailoring of adjuvant function: the role in vaccine development.

    Science.gov (United States)

    Prashant, Chandravilas Keshvan; Kumar, Manoj; Dinda, Amit Kumar

    2014-09-01

    Vaccination is one of the most powerful therapeutic tools for prevention and management of various infective and non-infective diseases including malignancy. Mass vaccination is a great strategy for eradicating major infectious diseases throughout the world like small pox. Application of nanotechnology for antigen delivery is a unique area of research and development which can change the vaccination strategy and policy in future. Nanocarriers can enhance antigen presentation including modulation of antigen processing pathways according to the specific need. The current review explores the pros and cons of application of different nanomaterials for antigen presentation and vaccine development.

  16. Present status of human papillomavirus vaccine development and implementation.

    Science.gov (United States)

    Herrero, Rolando; González, Paula; Markowitz, Lauri E

    2015-05-01

    Oncogenic human papillomavirus (HPV) infection is the cause of nearly all cervical cancers and a proportion of other anogenital and oropharyngeal cancers. A bivalent vaccine containing HPV 16 and 18 and a quadrivalent vaccine containing HPV 6, 11, 16, and 18 antigens are in use in vaccination programmes around the world. In clinical trials, three vaccine doses provided 90-100% protection against cervical infection and pre-cancer related to HPV 16 and 18 in women aged 15-26 years who were not infected at vaccination. Partial cross-protection against other HPV types has been reported but its duration is unknown. The vaccines were also efficacious at the prevention of HPV 16 and 18 infections at other anatomical sites in both sexes. Immunobridging studies allowed licensing of the vaccines for use starting at age 9 years for both sexes. Two-dose schedules elicit high antibody concentrations, leading to the recommendation of two-dose schedules for girls aged 9-14 years. Pre-licensure and post-licensure studies have provided data supporting vaccine safety. In 2014, a nonavalent vaccine containing HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 antigens was licensed by the US Food and Drug Administration. HPV vaccination was first introduced in high-income countries owing to vaccine cost, logistic challenges, and competing health priorities. Since 2011, vaccine prices have lowered, allowing the introduction of the vaccine in some middle-income countries. Funding of the vaccine by the GAVI Alliance in 2012 led to demonstration projects in some low-income countries. By 2014, more than 57 countries had included the HPV vaccine in their national health programmes. Data from several countries have shown the effect of vaccination on HPV infection and associated disease, and provided evidence of herd immunity. Expansion of programmes to countries with the highest burden of disease is beginning, but further efforts are needed to realise the potential of HPV vaccines. Copyright © 2015

  17. From empiricism to rational design: a personal perspective of the evolution of vaccine development.

    Science.gov (United States)

    De Gregorio, Ennio; Rappuoli, Rino

    2014-07-01

    Vaccination, which is the most effective medical intervention that has ever been introduced, originated from the observation that individuals who survived a plague or smallpox would not get the disease twice. To mimic the protective effects of natural infection, Jenner - and later Pasteur - inoculated individuals with attenuated or killed disease-causing agents. This empirical approach inspired a century of vaccine development and the effective prophylaxis of many infectious diseases. From the 1980s, several waves of new technologies have enabled the development of novel vaccines that would not have been possible using the empirical approach. The technological revolution in the field of vaccination is now continuing, and it is delivering novel and safer vaccines. In this Timeline article, we provide our views on the transition from empiricism to rational vaccine design.

  18. The introduction of new vaccines into developing countries. IV: Global Access Strategies.

    Science.gov (United States)

    Mahoney, Richard T; Krattiger, Anatole; Clemens, John D; Curtiss, Roy

    2007-05-16

    This paper offers a framework for managing a comprehensive Global Access Strategy for new vaccines in developing countries. It is aimed at strengthening the ability of public-sector entities to reach their goals. The Bill and Melinda Gates Foundation and The Rockefeller Foundation have been leaders in stimulating the creation of new organizations - public/private product development partnerships (PDPs) - that seek to accelerate vaccine development and distribution to meet the health needs of the world's poor. Case studies of two of these PDPs - the Salmonella Anti-pneumococcal Vaccine Program and the Pediatric Dengue Vaccine Initiative - examine development of such strategies. Relying on the application of innovation theory, the strategy leads to the identification of six Components of Innovation which cover all aspects of the vaccine innovation process. Appropriately modified, the proposed framework can be applied to the development and introduction of other products in developing countries including drugs, and nutritional and agricultural products.

  19. [Advances in the development of new vaccines against tuberculosis. 100 years after the introduction of BCG].

    Science.gov (United States)

    Krysztopa-Grzybowska, Katarzyna; Lutyńska, Anna

    2014-06-09

    The BCG vaccine used in the world for nearly 100 years protects children against the most severe forms of tuberculosis, but its effectiveness in preventing the most commonly occurring tuberculosis and the one burdened with the highest risk of transmission in adults is very diverse. Contraindications for BCG vaccination include HIV infection and other conditions of immunosuppression. Tuberculosis is a global problem difficult to control because of three main reasons: poor diagnostics in developing countries, long-term therapy or discontinuation of treatment resulting in the emergence of drug-resistant mycobacteria, and the availability of a TB vaccine which only protects children from the most severe forms of tuberculosis. BCG has little to no efficacy in preventing the most common adult pulmonary TB. The development of a more effective vaccine against tuberculosis is undoubtedly still a public health priority in order to improve control of the disease throughout the world. Elimination of TB as a global public health goal by 2050 is particularly ambitious and its achievement depends on the development and application of new intervention measures and newly designed vaccines. Currently, 14 newly developed products are undergoing clinical trials. These include a prophylactic vaccine capable of replacing the current BCG, booster vaccines to increase the effects of BCG, and therapeutic vaccines. The aim of the study is to present the current state of knowledge on cutting-edge research into new vaccines against tuberculosis, their efficacy, immunogenicity and potential use in the future.

  20. Advances in the development of new vaccines against tuberculosis. 100 years after the introduction of BCG

    Directory of Open Access Journals (Sweden)

    Katarzyna Krysztopa-Grzybowska

    2014-06-01

    Full Text Available The BCG vaccine used in the world for nearly 100 years protects children against the most severe forms of tuberculosis, but its effectiveness in preventing the most commonly occurring tuberculosis and the one burdened with the highest risk of transmission in adults is very diverse. Contraindications for BCG vaccination include HIV infection and other conditions of immunosuppression. Tuberculosis is a global problem difficult to control because of three main reasons: poor diagnostics in developing countries, long-term therapy or discontinuation of treatment resulting in the emergence of drug-resistant mycobacteria, and the availability of a TB vaccine which only protects children from the most severe forms of tuberculosis. BCG has little to no efficacy in preventing the most common adult pulmonary TB. The development of a more effective vaccine against tuberculosis is undoubtedly still a public health priority in order to improve control of the disease throughout the world. Elimination of TB as a global public health goal by 2050 is particularly ambitious and its achievement depends on the development and application of new intervention measures and newly designed vaccines. Currently, 14 newly developed products are undergoing clinical trials. These include a prophylactic vaccine capable of replacing the current BCG, booster vaccines to increase the effects of BCG, and therapeutic vaccines. The aim of the study is to present the current state of knowledge on cutting-edge research into new vaccines against tuberculosis, their efficacy, immunogenicity and potential use in the future.

  1. Dendritic cell-targeting DNA-based mucosal adjuvants for the development of mucosal vaccines

    OpenAIRE

    Kataoka, Kosuke; Fujihashi, Kohtaro

    2009-01-01

    In order to establish effective mucosal immunity against various mucosal pathogens, vaccines must be delivered via the mucosal route and contain effective adjuvant(s). Since mucosal adjuvants can simply mix with the antigen, it is relatively easy to adapt them for different types of vaccine development. Even in simple admixture vaccines, the adjuvant itself must be prepared without any complications. Thus, CpG oligodeoxynucleotides or plasmids encoding certain cDNA(s) would be potent mucosal ...

  2. Development of mismatch amplification mutation assays for the differentiation of MS1 vaccine strain from wild-type Mycoplasma synoviae and MS-H vaccine strains

    Science.gov (United States)

    Kreizinger, Zsuzsa; Sulyok, Kinga Mária; Grózner, Dénes; Bekő, Katinka; Dán, Ádám; Szabó, Zoltán

    2017-01-01

    Mycoplasma synoviae is an economically significant pathogen in the poultry industry, inducing respiratory disease and infectious synovitis in chickens and turkeys, and eggshell apex abnormality in chickens. Eradication, medication and vaccination are the options for controlling M. synoviae infection. Currently there are two commercial, live, attenuated vaccines available against M. synoviae: the temperature sensitive MS-H vaccine strain and the NAD independent MS1 vaccine strain. Differentiation of vaccine strains from field isolates is essential during vaccination and eradication programs. The present study provides melt-curve and agarose gel based mismatch amplification mutation assays (MAMA) to discriminate the MS1 vaccine strain from the MS-H vaccine strain and wild-type M. synoviae isolates. The assays are based on the A/C single nucleotide polymorphism at nt11 of a HIT family protein coding gene. The melt- and agarose-MAMAs reliably distinguish the MS1 vaccine strain genotype from the MS-H vaccine strain and wild-type M. synoviae isolate genotype from 102 template number/DNA sample. No cross-reactions with other avian Mycoplasma species were observed. The assays can be performed directly on clinical samples and they can be run simultaneously with the previously described MAMAs designed for the discrimination of the MS-H vaccine strain. The developed assays are applicable in laboratories with limited facilities and promote the rapid, simple and cost effective differentiation of the MS1 vaccine strain. PMID:28419134

  3. Development of a BCG challenge model for the testing of vaccine candidates against tuberculosis in cattle.

    Science.gov (United States)

    Villarreal-Ramos, Bernardo; Berg, Stefan; Chamberlain, Laura; McShane, Helen; Hewinson, R Glyn; Clifford, Derek; Vordermeier, Martin

    2014-09-29

    Vaccination is being considered as part of a sustainable strategy for the control of bovine tuberculosis (BTB) in the UK. The live attenuated Mycobacterium bovis bacillus Calmette-Guerin (BCG) has been used experimentally to vaccinate cattle against BTB. However, BCG confers partial protection against BTB and therefore, there is a need to develop improved vaccines. BTB vaccine efficacy experiments require the use of biosafety level 3 facilities which are expensive to maintain, generally oversubscribed and represent a bottle neck for the testing of vaccine candidates. One indicator of the induction of protective responses would be the ability of the host's immune response to control/kill mycobacteria. In this work we have evaluated an intranodal BCG challenge for the selection of vaccine candidates at biosafety level 2 which are capable of inducing mycobactericidal responses. To our knowledge, this is the first such report. Whilst BCG only confers partial protection, it is still the standard against which other vaccines are judged. Therefore we tested the BCG intranodal challenge in BCG (Danish strain) vaccinated cattle and showed that vaccinated cattle had lower BCG cfu counts than naïve cattle at 14 and 21 days after intranodal challenge with BCG (Tokyo strain). This model could help prioritize competing TB vaccine candidates and exploration of primary and secondary immune responses to mycobacteria. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

  4. Varicella zoster vaccines and their implications for development of HSV vaccines

    Energy Technology Data Exchange (ETDEWEB)

    Gershon, Anne A., E-mail: aag1@columbia.edu [Department of Pediatrics, Columbia University College of Physicians and Surgeons, 620W. 168th Street, NY, NY 10032 (United States)

    2013-01-05

    Live attenuated vaccines to prevent varicella and zoster have been available in the US for the past 17 years, with a resultant dramatic decrease in varicella incidence and a predicted future decrease in the incidence of zoster. The pathogenesis and immune responses to varicella zoster virus (VZV) as well as the safety and effectiveness of VZV vaccines are reviewed. The lack of sterilizing immunity provided by VZV vaccines has not prevented them from being safe and effective. Virological and pathological information concerning parallels and differences between VZV and herpes simplex virus (HSV) are highlighted. Although VZV and HSV are distinct pathogens, they appear to have similarities in target organs and immunity that provide an expectation of a high likelihood for the success of vaccination against HSV, and predicted to be similar to that of VZV.

  5. Emerging markets & emerging needs: developing countries vaccine manufacturers' perspective & its current status.

    Science.gov (United States)

    Jadhav, Suresh S; Gautam, Manish; Gairola, Sunil

    2009-06-01

    The success of vaccination has remained an important contribution towards public health in both industrialised and developing countries. However, there are still unmet public health needs in vaccine preventable diseases owing to issues related to affordability, supply, public awareness, research and development, intellectual property, skilled human resource, etc. Various global initiatives are being taken to tackle such issues. DCVMN, Developing Country Vaccine Manufacturers' Network, is one of such novel initiatives by developing countries, and is playing an important role in facilitating cheaper and quality vaccines to children of the world. DCVMN has become an international body for emerging vaccine manufacturers from the developing world. This manuscript provides an overview of DCVMN with respect to its origin, objectives, achievements, limitations and expectations.

  6. Next generation dengue vaccines: A review of the preclinical development pipeline.

    Science.gov (United States)

    Vannice, Kirsten S; Roehrig, John T; Hombach, Joachim

    2015-12-10

    Dengue represents a significant and growing public health problem across the globe, with approximately half of the world's population at risk. The increasing and expanding burden of dengue has highlighted the need for new tools to prevent dengue, including development of dengue vaccines. Recently, the first dengue vaccine candidate was evaluated in Phase 3 clinical trials, and other vaccine candidates are under clinical evaluation. There are also a number of candidates in preclinical development, based on diverse technologies, with promising results in animal models and likely to move into clinical trials and could eventually be next-generation dengue vaccines. This review provides an overview of the various technological approaches to dengue vaccine development with specific focus on candidates in preclinical development and with evaluation in non-human primates. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  7. Scaling up development, production of CBPP vaccine for cattle in ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    This project will allow researchers from Canada and Kenya to field trial a vaccine for contagious bovine pleuropneumonia. This endemic livestock disease affects the livelihoods of more than 24 million cattle producers and results in annual losses estimated at US$1 billion across sub-Saharan Africa. About the vaccine Using ...

  8. Progress in the development of vaccines against rumen methanogens.

    Science.gov (United States)

    Wedlock, D N; Janssen, P H; Leahy, S C; Shu, D; Buddle, B M

    2013-06-01

    Vaccination against rumen methanogens offers a practical approach to reduce methane emissions in livestock, particularly ruminants grazing on pasture. Although successful vaccination strategies have been reported for reducing the activity of the rumen-dwelling organism Streptococcus bovis in sheep and S. bovis and Lactobacillus spp. in cattle, earlier approaches using vaccines based on whole methanogen cells to reduce methane production in sheep have produced less promising results. An anti-methanogen vaccine will need to have broad specificity against methanogens commonly found in the rumen and induce antibody in saliva resulting in delivery of sufficiently high levels of antibodies to the rumen to reduce methanogen activity. Our approach has focussed on identifying surface and membrane-associated proteins that are conserved across a range of rumen methanogens. The identification of potential vaccine antigens has been assisted by recent advances in the knowledge of rumen methanogen genomes. Methanogen surface proteins have been shown to be immunogenic in ruminants and vaccination of sheep with these proteins induced specific antibody responses in saliva and rumen contents. Current studies are directed towards identifying key candidate antigens and investigating the level and types of salivary antibodies produced in sheep and cattle vaccinated with methanogen proteins, stability of antibodies in the rumen and their impact on rumen microbial populations. In addition, there is a need to identify adjuvants that stimulate high levels of salivary antibody and are suitable for formulating with protein antigens to produce a low-cost and effective vaccine.

  9. Development of a Human Papillomavirus Vaccination Intervention for Australian Adolescents

    Science.gov (United States)

    Cooper, Spring C.; Davies, Cristyn; McBride, Kate; Blades, Joanna; Stoney, Tanya; Marshall, Helen; Skinner, S. Rachel

    2016-01-01

    Objective: Australia has implemented a nation-wide programme providing a human papillomavirus (HPV) vaccine to girls and boys through school-based programmes. Previous research has identified three distinct areas for attention: (1) lack of understanding about HPV and HPV vaccination, (2) young people's desire for involvement in decision-making…

  10. Recent Developments in Livestock and Wildlife Brucellosis Vaccination

    Science.gov (United States)

    Live attenuated brucellosis vaccines have been available for protecting domestic livestock against B. melitensis or B. abortus for more than 60 years. Current vaccines are effective in preventing abortion and transmission of brucellosis, but poor at preventing infection or seroconversion. In addit...

  11. Approaches toward the development of DNA vaccine for influenza ...

    African Journals Online (AJOL)

    The main goals of this investigation were to prepare a viral DNA vaccine to help stimulate the immune system of poultry and to increase the efficiency of this vaccine. To accomplish this work, a strain of H5N1 circulating in Egypt was confirmed using rapid diagnostic methods and also, reverse transcriptase polymerase chain ...

  12. Plant glycans: friend or foe in vaccine development?

    NARCIS (Netherlands)

    Bosch, H.J.; Schots, A.

    2010-01-01

    Plants are an attractive platform for the production of N-glycosylated subunit vaccines. Wild type glycosylation of plants can be exploited to produce vaccines that antigen-presenting cells effectively take up, degrade and present to cells of the adaptive immune system. Alternatively,

  13. Developments in the formulation and delivery of spray dried vaccines

    NARCIS (Netherlands)

    Kanojia, Gaurav; Have, Rimko Ten; Soema, Peter C; Frijlink, Henderik; Amorij, Jean-Pierre; Kersten, Gideon

    2017-01-01

    Spray drying is a promising method for the stabilization of vaccines, which are usually formulated as liquids. Usually, vaccine stability is improved by spray drying in the presence of a range of excipients. Unlike freeze drying, there is no freezing step involved, thus the damage related to this

  14. Systems biology applied to vaccine and immunotherapy development

    Directory of Open Access Journals (Sweden)

    Marincola Francesco M

    2011-09-01

    Full Text Available Abstract Immunotherapies, including vaccines, represent a potent tool to prevent or contain disease with high morbidity or mortality such as infections and cancer. However, despite their widespread use, we still have a limited understanding of the mechanisms underlying the induction of protective immune responses. Immunity is made of a multifaceted set of integrated responses involving a dynamic interaction of thousands of molecules; among those is a growing appreciation for the role the innate immunity (i.e. pathogen recognition receptors - PRRs plays in determining the nature and duration (immune memory of adaptive T and B cell immunity. The complex network of interactions between immune manipulation of the host (immunotherapy on one side and innate and adaptive responses on the other might be fully understood only employing the global level of investigation provided by systems biology. In this framework, the advancement of high-throughput technologies, together with the extensive identification of new genes, proteins and other biomolecules in the "omics" era, facilitate large-scale biological measurements. Moreover, recent development of new computational tools enables the comprehensive and quantitative analysis of the interactions between all of the components of immunity over time. Here, we review recent progress in using systems biology to study and evaluate immunotherapy and vaccine strategies for infectious and neoplastic diseases. Multi-parametric data provide novel and often unsuspected mechanistic insights while enabling the identification of common immune signatures relevant to human investigation such as the prediction of immune responsiveness that could lead to the improvement of the design of future immunotherapy trials. Thus, the paradigm switch from "empirical" to "knowledge-based" conduct of medicine and immunotherapy in particular, leading to patient-tailored treatment.

  15. Accelerating vaccine development and deployment: report of a Royal Society satellite meeting.

    Science.gov (United States)

    Bregu, Migena; Draper, Simon J; Hill, Adrian V S; Greenwood, Brian M

    2011-10-12

    The Royal Society convened a meeting on the 17th and 18th November 2010 to review the current ways in which vaccines are developed and deployed, and to make recommendations as to how each of these processes might be accelerated. The meeting brought together academics, industry representatives, research sponsors, regulators, government advisors and representatives of international public health agencies from a broad geographical background. Discussions were held under Chatham House rules. High-throughput screening of new vaccine antigens and candidates was seen as a driving force for vaccine discovery. Multi-stakeholder, small-scale manufacturing facilities capable of rapid production of clinical grade vaccines are currently too few and need to be expanded. In both the human and veterinary areas, there is a need for tiered regulatory standards, differentially tailored for experimental and commercial vaccines, to allow accelerated vaccine efficacy testing. Improved cross-fertilization of knowledge between industry and academia, and between human and veterinary vaccine developers, could lead to more rapid application of promising approaches and technologies to new product development. Identification of best-practices and development of checklists for product development plans and implementation programmes were seen as low-cost opportunities to shorten the timeline for vaccine progression from the laboratory bench to the people who need it.

  16. R&D in Vaccines Targeting Neglected Diseases: An Exploratory Case Study Considering Funding for Preventive Tuberculosis Vaccine Development from 2007 to 2014

    Directory of Open Access Journals (Sweden)

    Theolis Costa Barbosa Bessa

    2017-01-01

    Full Text Available Based on an exploratory case study regarding the types of institutions funding the research and development to obtain new tuberculosis vaccines, this article intends to provoke discussion regarding the provision of new vaccines targeting neglected disease. Although our findings and discussion are mainly relevant to the case presented here, some aspects are more generally applicable, especially regarding the dynamics of development in vaccines to prevent neglected diseases. Taking into account the dynamics of innovation currently seen at work in the vaccine sector, a highly concentrated market dominated by few multinational pharmaceutical companies, we feel that global PDP models can play an important role throughout the vaccine development cycle. In addition, the authors call attention to issues surrounding the coordination of actors and resources in the research, development, manufacturing, and distribution processes of vaccine products arising from PDP involvement.

  17. RTS,S malaria vaccine development: progress and considerations for postapproval introduction

    Directory of Open Access Journals (Sweden)

    Asante KP

    2016-06-01

    Full Text Available Kwaku Poku Asante, George Adjei, Yeetey Enuameh, Seth Owusu-Agyei Kintampo Health Research Centre, Kintampo, Brong Ahafo Region, Ghana Abstract: Though the burden of malaria has decreased in the last decade in some sub-Saharan African countries, it is still high in others, and there is no malaria vaccine in use. The development of malaria vaccines in combination with current control programs could be effective in reducing the malaria burden. In this paper, we review and discuss the progress made in the RTS,S malaria vaccine development and considerations for its postapproval process. We conclude that the development of malaria vaccines has been a long process confronted with challenges of funding, difficulty in identifying malaria antigens that correlate with protection, and development of adjuvant systems among others. The scientific approval of the vaccine by the European Medicines Agency in July 2015 and subsequent recommendations for pilot implementation studies by the World Health Organization made history as the first human parasite vaccine. It is also a major public health achievement as the vaccine has the potential to prevent thousands of malaria cases. However, there are implementation challenges such as cold chain systems, community acceptance, and monitoring of adverse events post-licensure that need to be carefully addressed. Keywords: malaria, vaccines, challenges, introduction, Africa, implementation considerations 

  18. Development of a classical swine fever subunit marker vaccine and companion diagnostic test

    NARCIS (Netherlands)

    Moormann, R.J.; Bouma, A.; Kramps, J.A.; Terpstra, C.; Smit, de H.J.

    2000-01-01

    The development of a classical swine fever (CSF) subunit marker vaccine, based on viral envelope glycoprotein E2, and a companion diagnostic test, based on a second viral envelope glycoprotein E(RNS), will be described. Important properties of the vaccine, such as onset and duration of immunity, and

  19. Establishing the pig as a large animal model for vaccine development against human cancer

    DEFF Research Database (Denmark)

    Overgaard, Nana Haahr; Frøsig, Thomas Mørch; Welner, Simon

    2015-01-01

    and the porcine immunome is closer related to the human counterpart, we here introduce pigs as a supplementary large animal model for human cancer vaccine development. IDO and RhoC, both important in human cancer development and progression, were used as vaccine targets and 12 pigs were immunized with overlapping......C-derived peptides across all groups with no adjuvant being superior. These findings support the further use of pigs as a large animal model for vaccine development against human cancer.......Immunotherapy has increased overall survival of metastatic cancer patients, and cancer antigens are promising vaccine targets. To fulfill the promise, appropriate tailoring of the vaccine formulations to mount in vivo cytotoxic T cell (CTL) responses toward co-delivered cancer antigens is essential...

  20. Development of a DNA vaccine targeting human papillomavirus type 16 oncoprotein E6.

    Science.gov (United States)

    Peng, Shiwen; Ji, Hongxiu; Trimble, Cornelia; He, Liangmei; Tsai, Ya-Chea; Yeatermeyer, Jessica; Boyd, David A K; Hung, Chien-Fu; Wu, T-C

    2004-08-01

    Human papillomavirus (HPV), particularly type 16 (HPV-16), is present in more than 99% of cervical cancers. The HPV oncoproteins E6 and E7 are constantly expressed and therefore represent ideal targets for HPV vaccine development. We previously developed DNA vaccines encoding calreticulin (CRT) linked to HPV-16 E7 and generated potent E7-specific CD8(+) T-cell immune responses and antitumor effects against an E7-expressing tumor. Since vaccines targeting E6 also represent an important strategy for controlling HPV-associated lesions, we developed a DNA vaccine encoding CRT linked to E6 (CRT/E6). Our results indicated that the CRT/E6 DNA vaccine, but not a wild-type E6 DNA vaccine, generated significant E6-specific CD8(+) T-cell immune responses in vaccinated mice. Mapping of the immunodominant epitope of E6 revealed that an E6 peptide comprising amino acids (aa) 48 to 57 (E6 aa48-57), presented by H-2K(b), is the optimal peptide and that the region of E6 comprising aa 50 to 57 represents the minimal core sequence required for activating E6-specific CD8(+) T lymphocytes. We also demonstrated that E6 aa48-57 contains cytotoxic T-lymphocyte epitopes naturally presented by E6-expressing TC-1 cells. Vaccination with a CRT/E6 but not a CRT/mtE6 (lacking aa 50 to 57 of E6) DNA vaccine could protect vaccinated mice from challenge with E6-expressing TC-1 tumors. Thus, our data indicate that E6 aa48-57 contains the immunodominant epitope and that a CRT/E6 DNA vaccine may be useful for control of HPV infection and HPV-associated lesions.

  1. Vaccines for bovine neosporosis: current status and key aspects for development.

    Science.gov (United States)

    Horcajo, P; Regidor-Cerrillo, J; Aguado-Martínez, A; Hemphill, A; Ortega-Mora, L M

    2016-12-01

    Bovine neosporosis is a worldwide concern due to its global distribution and great economic impact. Reproductive failure in cattle due to abortion leads to major economic losses associated with the disease. Currently, there is no treatment or vaccine available against abortion or transmission caused by Neospora caninum infection in cattle. However, vaccination is considered the best measure of control against bovine neosporosis. Several host and parasite factors can influence the dynamics of the infection in bovines. Moreover, the availability of well-defined infection models is a key factor for the evaluation of vaccine candidates. However, working with cattle is not easy due to difficult handling, facilities and costs, and therefore, 'more affordable' models could be used for screening of promising vaccines to establish proof of concept. So far, live-attenuated vaccines have shown good efficacy against exogenous transplacental transmission; however, they have relevant disadvantages and associated risks, which render inactivated or subunit vaccines the best way forward. The identification of novel potential targets and vaccines, and the application of innovative vaccine technologies in harmonized experimental animal models, will accelerate the development of an effective vaccine against bovine neosporosis. © 2016 John Wiley & Sons Ltd.

  2. The study of H. pylori putative candidate factors for single- and multi-component vaccine development.

    Science.gov (United States)

    Mirzaei, Nasrin; Poursina, Farkhondeh; Moghim, Sharareh; Rashidi, Niloufar; Ghasemian Safaei, Hajieh

    2017-09-01

    Helicobacter pylori has grown to colonize inside the stomach of nearly half of the world's population, turning into the most prevalent infections in the universe. Medical care failures noticeably confirm the need for a vaccine to hinder or deal with H. pylori. This review is planned to discuss the most known factors as a vaccine candidate, including single (AhpC, BG, CagA, KatA, Fla, Hsp, HWC, Lpp, LPS, NAP, OMP, OMV, SOD, Tpx, Urease, VacA) and multi-component vaccines. Many promising results in the field of single and multivalent vaccine can be seen, but there is no satisfactory outcome and neither a prophylactic nor a therapeutic vaccine to treat or eradicate the infection in human has been acquired. Hence, selecting suitable antigen is an important factor as an appropriate adjuvant. Taken all together, the development of efficient anti-H. pylori vaccines relies on the fully understanding of the interactions between H. pylori and its host immune system. Therefore, more work should be done on epitope mapping, analysis of molecular structure, and determination of the antigen determinant region as well due to design a vaccine, preferably a multi-component vaccine to elicit specific CD4 T-cell responses that are required for H. pylori vaccine efficacy.

  3. Development of Human Papillomavirus (HPV) Vaccines: A Review of Literature and Clinical Update.

    Science.gov (United States)

    Sangar, Vikrant Chadrakant; Ghongane, Balasaheb; Mathur, Gaurav

    2016-01-01

    The casual relationship concerning Human papillomaviruses (HPV) and cervical cancer is already established. Therefore, such HPV-associated malignancies might be prevented by prophylactic HPV vaccines. From 2009, two prophylactic HPV L1 Virus-Like Particle vaccines namely, Gardasil®; - quadrivalent (Merck) and Cervarix™ - bivalent (GlaxoSmithKline) are widely commercially available. By Aug 2014, 58 countries had introduced HPV vaccination in their national immunization program; this has led to numerous publications on safety and real world effectiveness. We have also seen long-term immunogenicity and efficacy data emerging. Data on cross-protection has also evolved. In clinical trials, it is observed that vaccinating adolescents results in higher immunological response than young adults hence to achieve best HPV vaccine efficacy it is advisable to immunize before the onset of sexual activity. Recently we have seen development of 2 dose vaccine schedule for adolescent, and emerging evidences even point that single dose of HPV vaccines can result in high efficacy, this observation is currently under consideration but if accepted will greatly impact vaccination coverage. In terms of safety, pregnancy registry did not find any unexpected patterns in fetal or maternal outcomes. This review only focuses on the efficacy and safety data of both Food and Drug Administration approved vaccines from clinical phase I to phase IV.

  4. A systematic review and meta-analysis for the adverse effects, immunogenicity and efficacy of Lyme disease vaccines: Guiding novel vaccine development.

    Science.gov (United States)

    Badawi, Alaa; Shering, Maria; Rahman, Shusmita; Lindsay, L Robbin

    2017-04-20

    Lyme borreliosis (LB) is the most prevalent arthropod-borne infectious disease in North America. Currently, no vaccine is available to prevent LB in humans, although monovalent and multivalent vaccines have been developed in the past. The aim of the current study is to conduct a systematic review and meta-analysis to evaluate and compare the findings from these two classes of vaccines for their reactogenicity, immunogenicity and efficacy, in the hope this may assist in the development of future vaccines. A search strategy was developed for online databases (PubMed, Ovid MEDLINE, and Embase). Search terms used were "vaccine/vaccination", "Lyme disease/Borreliosis", "clinical trial(s)" and "efficacy". Only seven clinical trials were included to compare the results of the monovalent vaccines to those of the multivalent one. Meta-analyses were conducted to evaluate the reactogenicity and immunogenicity of the two vaccine classes. Odds ratio (OR) for LB (and 95% confidence intervals; 95% CI) were calculated for the efficacy of the monovalent vaccine from three different clinical trials at different dose schedules. Incidence of redness (local adverse effect) and fever (systemic side effect) were, respectively, 6.8- and 2.9-fold significantly lower (p < 0.05) in individuals who received multivalent vaccines compared to those receiving the monovalent one. Incidences of all other local and systemic adverse effects were non-significantly lower in the multivalent vaccine compared to the monovalent vaccines. Seroprotection was comparable among individuals who received the two vaccine classes at the 30 μg dose level. Efficacy in the prevention of LB was only evaluated for the monovalent vaccines. OR of LB ranged from 0.49 (95% CI: 0.14-0.70; p < 0.005, vs. placebo) to 0.31 (95% CI: 0.26-0.63; p < 0.005) for the initial and final doses respectively, with an overall OR of 0.4 (95% CI: 0.26-0.63, p < 0.001). The current study further validates that the monovalent and multivalent

  5. Approaches and Perspectives for Development of African Swine Fever Virus Vaccines

    Directory of Open Access Journals (Sweden)

    Marisa Arias

    2017-10-01

    Full Text Available African swine fever (ASF is a complex disease of swine, caused by a large DNA virus belonging to the family Asfarviridae. The disease shows variable clinical signs, with high case fatality rates, up to 100%, in the acute forms. ASF is currently present in Africa and Europe where it circulates in different scenarios causing a high socio-economic impact. In most affected regions, control has not been effective in part due to lack of a vaccine. The availability of an effective and safe ASFV vaccines would support and enforce control–eradication strategies. Therefore, work leading to the rational development of protective ASF vaccines is a high priority. Several factors have hindered vaccine development, including the complexity of the ASF virus particle and the large number of proteins encoded by its genome. Many of these virus proteins inhibit the host’s immune system thus facilitating virus replication and persistence. We review previous work aimed at understanding ASFV–host interactions, including mechanisms of protective immunity, and approaches for vaccine development. These include live attenuated vaccines, and “subunit” vaccines, based on DNA, proteins, or virus vectors. In the shorter to medium term, live attenuated vaccines are the most promising and best positioned candidates. Gaps and future research directions are evaluated.

  6. Malaria Vaccine Development: Are Bacterial Flagellin Fusion Proteins the Bridge between Mouse and Humans?

    Directory of Open Access Journals (Sweden)

    Daniel Y. Bargieri

    2011-01-01

    Full Text Available In the past 25 years, the development of an effective malaria vaccine has become one of the biggest riddles in the biomedical sciences. Experimental data using animal infection models demonstrated that it is possible to induce protective immunity against different stages of malaria parasites. Nonetheless, the vast body of knowledge has generated disappointments when submitted to clinical conditions and presently a single antigen formulation has progressed to the point where it may be translated into a human vaccine. In parallel, new means to increase the protective effects of antigens in general have been pursued and depicted, such as the use of bacterial flagellins as carriers/adjuvants. Flagellins activate pathways in the innate immune system of both mice and humans. The recent report of the first Phase I clinical trial of a vaccine containing a Salmonella flagellin as carrier/adjuvant may fuel the use of these proteins in vaccine formulations. Herein, we review the studies on the use of recombinant flagellins as vaccine adjuvants with malarial antigens in the light of the current state of the art of malaria vaccine development. The available information indicates that bacterial flagellins should be seriously considered for malaria vaccine formulations to the development of effective human vaccines.

  7. Carbohydrate vaccines: developing sweet solutions to sticky situations?

    Science.gov (United States)

    Astronomo, Rena D.; Burton, Dennis R.

    2013-01-01

    The realm of carbohydrate vaccines has expanded far beyond the capsular polysaccharides of bacterial pathogens to include a diverse collection of targets representing nearly every biological kingdom. Recent technological advances in glycobiology and glycochemistry are paving the way for a new era in carbohydrate vaccine design enabling greater efficiency in the identification, synthesis and evaluation of unique glycan epitopes found on a plethora of pathogens and malignant cells. This article reviews the progress being made in addressing challenges posed by targeting the surface carbohydrates of bacteria, protozoa, helminths, viruses, fungi and cancer for vaccine purposes. PMID:20357803

  8. Improving immunogenicity, efficacy and safety of vaccines through innovation in clinical assay development and trial design: the Phacilitate Vaccine Forum, Washington D.C. 2011.

    Science.gov (United States)

    Moldovan, Ioana R; Tary-Lehmann, Magdalena

    2011-06-01

    The 9th Annual Vaccine Forum organized by Phacilitate in Washington D.C. 2011 brought together 50+ senior level speakers and over 400 participants representing all the key stakeholders concerning vaccines. The main focus of the meeting was to define priorities in the global vaccines sector from funding to manufacturing and evaluation of vaccine efficacy. A special session was devoted to improving immunogenicity, efficacy and safety of vaccines through innovation in clinical assay development and trial design. The current regulatory approach to clinical assay specification, validation and standardization that enable more direct comparisons of efficacy between trials was illustrated by the success in meningococcal vaccine development. The industry approach to validation strategies was exemplified by a new serologic test used on the diagnostic of pneumococcal pneumonia. The application of the Animal Rule to bridge clinical and non-clinical studies in botulism has allowed significant progress in developing one of the first vaccines to seek approval under the FDA Animal Efficacy Rule. An example of pushing the boundaries in the correlation of immunological responses and efficacy points was represented by a recent cell-based influenza vaccine for which the same correlates of protection apply as for the traditional, egg-based flue vaccine. In the field of HIV phase 2b studies are underway, based on promising results obtained with some vaccine candidates. The conclusion of this session was that creativity in vaccine design and evaluation is beneficial and can lead to innovative new vaccine designs as well as to validated assays to assess vaccine efficacy.

  9. How the research-based industry approaches vaccine development and establishes priorities.

    Science.gov (United States)

    André, F E

    2002-01-01

    Over the past two decades, progress in immunology, molecular biology and genomics as well as some technological breakthroughs in computer science has opened the way to the development of prophylactic vaccines against most acute infectious diseases. Therapeutic vaccines against chronic infections, allergic conditions, auto-immune diseases and cancer have also come into the realm of possibility. It is estimated that wordwide there are about 400 vaccine projects in R&D laboratories of academic institutions, research institutes and vaccine manufacturers. Most of these projects will not yield a licensed vaccine for routine or even targeted immunisation. This is mostly not because of scientific barriers but due to financial and politicoeconomic obstades that make their development feasible only by the handful of major research-based vaccine manufacturers that nowadays all form part of large global pharmaceutical corporations. Such enterprises have to be profitable to survive and priority setting, when it comes to R&D projects, has to take into account potential return on all investments, particularly as it currently costs between 200 and 500 million US dollars to bring a new vaccine from the concept stage to market. Factors that influence the decision to embark upon an R&D project on a new vaccine include the medical need for the vaccine, gauged by the global burden of the targeted disease, potential and probable market size - judged on volume (number of doses required) and value (total sales) -, probability of success and expertise of the company in the field (both R&D and marketing) as well as the likelihood of competitors taking a large part of the market. Moral imperatives such as the urgent need for vaccines against HIV/AIDS, malaria and an improved vaccine against tuberculosis to save the several millions of lives claimed each year by these diseases also play a role. However, for such investments to be sustainable other sources of financing than the commercial

  10. Rapid development of a DNA vaccine for Zika virus.

    Science.gov (United States)

    Dowd, Kimberly A; Ko, Sung-Youl; Morabito, Kaitlyn M; Yang, Eun Sung; Pelc, Rebecca S; DeMaso, Christina R; Castilho, Leda R; Abbink, Peter; Boyd, Michael; Nityanandam, Ramya; Gordon, David N; Gallagher, John Robert; Chen, Xuejun; Todd, John-Paul; Tsybovsky, Yaroslav; Harris, Audray; Huang, Yan-Jang S; Higgs, Stephen; Vanlandingham, Dana L; Andersen, Hanne; Lewis, Mark G; De La Barrera, Rafael; Eckels, Kenneth H; Jarman, Richard G; Nason, Martha C; Barouch, Dan H; Roederer, Mario; Kong, Wing-Pui; Mascola, John R; Pierson, Theodore C; Graham, Barney S

    2016-10-14

    Zika virus (ZIKV) was identified as a cause of congenital disease during the explosive outbreak in the Americas and Caribbean that began in 2015. Because of the ongoing fetal risk from endemic disease and travel-related exposures, a vaccine to prevent viremia in women of childbearing age and their partners is imperative. We found that vaccination with DNA expressing the premembrane and envelope proteins of ZIKV was immunogenic in mice and nonhuman primates, and protection against viremia after ZIKV challenge correlated with serum neutralizing activity. These data not only indicate that DNA vaccination could be a successful approach to protect against ZIKV infection, but also suggest a protective threshold of vaccine-induced neutralizing activity that prevents viremia after acute infection. Copyright © 2016, American Association for the Advancement of Science.

  11. [The development of mucosal vaccine using bacterial function for targeting mucosal tissues].

    Science.gov (United States)

    Suzuki, Hidehiko; Kondoh, Masuo; Yagi, Kiyohito; Kiyono, Hiroshi; Kunisawa, Jun

    2014-01-01

    Most pathogens invade body through the mucosal epithelium, which is a primary target to prevent the infectious diseases. Mucosal vaccine has been considered to be an effective strategy to establish immunosurveillance against pathogens by the induction of antigen-specific immune responses at both mucosal and systemic immune compartments. The development of antigen delivery system and mucosal adjuvants are required for the sufficient induction of protective immunity in the development of mucosal vaccine. In this review, we shed light on the recent advances in the development of antigen delivery system using microbial functions for mucosal vaccines.

  12. Prospects and perspectives for development of a vaccine against herpes simplex virus infections.

    Science.gov (United States)

    McAllister, Shane C; Schleiss, Mark R

    2014-11-01

    Herpes simplex viruses 1 and 2 are human pathogens that lead to significant morbidity and mortality in certain clinical settings. The development of effective antiviral medications, however, has had little discernible impact on the epidemiology of these pathogens, largely because the majority of infections are clinically silent. Decades of work have gone into various candidate HSV vaccines, but to date none has demonstrated sufficient efficacy to warrant licensure. This review examines developments in HSV immunology and vaccine development published since 2010, and assesses the prospects for improved immunization strategies that may result in an effective, licensed vaccine in the near future.

  13. Ebola Virus: Immune Mechanisms of Protection and Vaccine Development

    OpenAIRE

    Nyamathi, AM; Fahey, JL; Sands, H; Casillas, AM

    2003-01-01

    Vaccination is one of our most powerful antiviral strategies. Despite the emergence of deadly viruses such as Ebola virus, vaccination efforts have focused mainly on childhood communicable diseases. Although Ebola virus was once believed to be limited to isolated outbreaks in distant lands, forces of globalization potentiate outbreaks anywhere in the world through incidental transmission. Moreover, since this virus has already been transformed into weapongrade material, the potential exists f...

  14. Status of vaccine research and development of vaccines for HIV-1.

    Science.gov (United States)

    Safrit, Jeffrey T; Fast, Patricia E; Gieber, Lisa; Kuipers, Hester; Dean, Hansi J; Koff, Wayne C

    2016-06-03

    Human immunodeficiency virus (HIV) is the cause of one of the most lethal pandemics in human history, although in recent years access to highly effective anti-retroviral therapy has provided new hope worldwide. Transmission of HIV by sexual contact, childbirth and injection drug use has been reduced, but 2 million are newly infected each year, and much of the transmission is from people who do not know their status. In addition to known methods, a preventive vaccine is needed to end the pandemic. The extraordinary mutability and genetic diversity of HIV is an enormous challenge, but vaccines are being designed for broad coverage. Computer-aided design of mosaic immunogens, incorporating many epitopes from the entire genome or from conserved regions aim to induce CD8+ T cells to kill virus-infected cells or inhibit virus replication, while trimeric envelope proteins or synthetic mimics aim to induce broadly reactive neutralizing antibodies similar to those cloned from some infected patients. Induction of more potent and durable responses may require new adjuvants or replicating chimeric vectors chimeras that bear HIV genes. Passive or genetic delivery of broadly neutralizing antibodies may provide broad protection and/or lead to insights for vaccine designers. Proof-of-concept trials in non-human primates and in one human efficacy trial have provided scientific clues for a vaccine that could provide broad and durable protection against HIV. The use of vaccines to destroy HIV reservoirs as part of therapy or cure is now also being explored. Copyright © 2016 World Health Organization. Published by Elsevier Ltd.. All rights reserved.

  15. Studies of the Outer Membrane Proteins of Campylobacter Jejuni for Vaccine Development

    Science.gov (United States)

    1991-11-26

    AD-A245 442 AD___1111111i1i11l 01 li[i ] i 1 I1 STUDIES OF THE OUTER MEMBRANE PROTEINS OF CAMPYLOBACTER JEJUNI FOR VACCINE DEVELOPMENT MIDTERM...the Outer Membrane Proteins of Campylobacter 90PP0820 Jejuni for Vaccine Development ____ ___ ___ ____ _ _ ___ ___ ___ ____ ___ ___61102A .1 6...Enteritis in Thailand. Although Campylobacter enteritis is usually an inflammatory process in developed countries, watery diarrhea is common in the

  16. VaxCelerate II: rapid development of a self-assembling vaccine for Lassa fever.

    Science.gov (United States)

    Leblanc, Pierre; Moise, Leonard; Luza, Cybelle; Chantaralawan, Kanawat; Lezeau, Lynchy; Yuan, Jianping; Field, Mary; Richer, Daniel; Boyle, Christine; Martin, William D; Fishman, Jordan B; Berg, Eric A; Baker, David; Zeigler, Brandon; Mais, Dale E; Taylor, William; Coleman, Russell; Warren, H Shaw; Gelfand, Jeffrey A; De Groot, Anne S; Brauns, Timothy; Poznansky, Mark C

    2014-01-01

    Development of effective vaccines against emerging infectious diseases (EID) can take as much or more than a decade to progress from pathogen isolation/identification to clinical approval. As a result, conventional approaches fail to produce field-ready vaccines before the EID has spread extensively. Lassa is a prototypical emerging infectious disease endemic to West Africa for which no successful vaccine is available. We established the VaxCelerate Consortium to address the need for more rapid vaccine development by creating a platform capable of generating and pre-clinically testing a new vaccine against specific pathogen targets in less than 120 d A self-assembling vaccine is at the core of the approach. It consists of a fusion protein composed of the immunostimulatory Mycobacterium tuberculosis heat shock protein 70 (MtbHSP70) and the biotin binding protein, avidin. Mixing the resulting protein (MAV) with biotinylated pathogen-specific immunogenic peptides yields a self-assembled vaccine (SAV). To meet the time constraint imposed on this project, we used a distributed R&D model involving experts in the fields of protein engineering and production, bioinformatics, peptide synthesis/design and GMP/GLP manufacturing and testing standards. SAV immunogenicity was first tested using H1N1 influenza specific peptides and the entire VaxCelerate process was then tested in a mock live-fire exercise targeting Lassa fever virus. We demonstrated that the Lassa fever vaccine induced significantly increased class II peptide specific interferon-γ CD4(+) T cell responses in HLA-DR3 transgenic mice compared to peptide or MAV alone controls. We thereby demonstrated that our SAV in combination with a distributed development model may facilitate accelerated regulatory review by using an identical design for each vaccine and by applying safety and efficacy assessment tools that are more relevant to human vaccine responses than current animal models.

  17. Immunogenic Apoptosis as a Novel Tool for Anticancer Vaccine Development

    Directory of Open Access Journals (Sweden)

    Barbara Montico

    2018-02-01

    Full Text Available Immunogenic apoptosis, or more appropriately called immunogenic cell death (ICD, is a recently described form of apoptosis induced by a specific set of chemotherapeutic drugs or by physical therapeutic modalities, such as ionizing irradiation and photodynamic therapy. The peculiar characteristic of ICD is the ability to favor recognition and elimination of dying tumor cells by phagocytes in association with the release of pro-inflammatory molecules (such as cytokines and high-mobility group box-1. While in vitro and animal models pointed to ICD as one of the molecular mechanisms mediating the clinical efficacy of some anticancer agents, it is hard to clearly demonstrate its contribution in cancer patients. Clinical evidence suggests that the induction of ICD alone is possibly not sufficient to fully subvert the immunosuppressive tumor microenvironment. However, interesting results from recent studies contemplate the exploitation of ICD for improving the immunogenicity of cancer cells to use them as an antigen cargo in the development of dendritic cell (DC vaccines. Herein, we discuss the effects of danger signals expressed or released by cancer cells undergoing ICD on the maturation and activation of immature and mature DC, highlighting the potential added value of ICD in adoptive immunotherapy protocols.

  18. TSOL18 Vaccine Antigen of Taenia solium: Development of Monoclonal Antibodies and Field Testing of the Vaccine in Cameroon

    Directory of Open Access Journals (Sweden)

    Assana, E.

    2010-01-01

    necropsy at the end of the trial (110 vaccinated; 102 controls. Viable T. solium cysticerci were identified in 20 control pigs (prevalence 19.6%, including 14 animals that had estimated total body burdens of > 1000 cysticerci. No cysticerci were found in any of the vaccinated animals indicating that the vaccine provided a very high level of protection (P< 0.0001 against naturally acquired infection with T. solium in pigs. Combined application of TSOL18 vaccination and a single oxfendazole treatment in pigs is a simple and relatively sustainable procedure that has the potential to control T. solium transmission in endemic areas and, indirectly, reduce the number of new cases of neurocysticercosis in humans. In chapter 6, the similarity of the antibody responses of pigs and mice to TSOL18 antigen is highlighted. Four IgG1 monoclonal antibodies (MoAb were produced against the conformational epitopes of TSOL18. It was shown that pig antisera inhibit the binding of these MoAbs in a competition ELISA, indicating that pig and mouse antibodies against TSOL18 vaccine react with the same conformational epitopes. For this reason, monoclonal antibodies raised in mice immunized with TSOL18 could be a valuable source of antibodies for further characterisation of the host-protective epitopes of the vaccine. A monoclonal antibody-based inhibitive enzyme-linked immunosorbent assay (mi-ELISA was developed. Serum samples of TSOL18-vaccinated and non-vaccinated pigs were used. In all the vaccinated and protected pigs screened at necropsy, anti-TSOL18 antibodies inhibited the binding of a monoclonal antibody (Mab25D12C1 specific to the conformational epitopes of TSOL18 antigen, suggesting an immune response that correlates with protection. This result was in agreement with the results obtained in an indirect ELISA, which showed that all the vaccinated and protected pigs had developed antibodies to the TSOL18 vaccine. In chapter 7 the efficacy of the TSOL18 vaccine is compared with that of

  19. Multi-stage subunit vaccine development against Mycobacterium paratuberculosis and Johne’s disease in ruminants

    DEFF Research Database (Denmark)

    Jungersen, Gregers

    , but in vaccination-challenge studies protection was not associated with level of FET-specific IFN-γ production, and Map-specific IFN-γ production appeared as a surrogate of disease with an inverse relationship to level of Map in tissues at slaughter. Polyfunctional T cells were induced by FET vaccination, but could...... in macrophages. The disease progression is very slow with neonatal animals being the most susceptible to infection, but without development of detectable IFN-γ responses for months after infection and rarely with clinical disease before the second or third year of life. Available whole cell vaccines against...... paratuberculosis provide only partial protection and interfere with diagnostic tests for JD and surveillance for bovine TB. In contrast, recombinant subunit vaccines can be designed to be used without compromising control of bTB and Map. Taking advantage of data from mouse TB studies, and early Map vaccination...

  20. Progress, prospects, and problems in Epstein-Barr virus vaccine development.

    Science.gov (United States)

    Balfour, Henry H

    2014-06-01

    Epstein-Barr virus (EBV) is responsible for a farrago of acute and chronic human diseases including cancer. A prophylactic vaccine could reduce this disease burden. Several EBV vaccines have been given to humans but none has been sufficiently studied to establish safety and efficacy. EBV vaccine development has been hampered by the lack of an animal model other than subhuman primates, proprietary issues, selection of an appropriate adjuvant, and failure to reach consensus on what an EBV vaccine could or should actually achieve. A recent conference at the U.S. National Institutes of Health emphasizing the global importance of EBV vaccine and advocating a phase 3 trial to prevent infectious mononucleosis should encourage research that could eventually lead to its licensure. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Pre-clinical and clinical development of the first placental malaria vaccine.

    Science.gov (United States)

    Pehrson, Caroline; Salanti, Ali; Theander, Thor G; Nielsen, Morten A

    2017-06-01

    Malaria during pregnancy is a massive health problem in endemic areas. Placental malaria infections caused by Plasmodium falciparum are responsible for up to one million babies being born with a low birth weight every year. Significant efforts have been invested into preventing the condition. Areas covered: Pub Med was searched using the broad terms 'malaria parasite placenta' to identify studies of interactions between parasite and host, 'prevention of placental malaria' to identify current strategies to prevent placental malaria, and 'placental malaria vaccine' to identify pre-clinical vaccine development. However, all papers from these searches were not systematically included. Expert commentary: The first phase I clinical trials of vaccines are well underway. Trials testing efficacy are more complicated to carry out as only women that are exposed to parasites during pregnancy will contribute to endpoint measurements, further it may require extensive follow-up to establish protection. Future second generation vaccines may overcome the inherent challenges in making an effective placental malaria vaccine.

  2. Development of a Multi-Stage Vaccine against Paratuberculosis in Cattle

    DEFF Research Database (Denmark)

    Thakur, Aneesh

    to considerable economic losses to farming community. Paratuberculosis is a staged infection in which young calves acquire the infection in the first months of life, may progress into a prolonged asymptomatic stage of about 2-5 years and may eventually become clinically infected animals. Vaccination with whole......-cell live or inactivated vaccines prevents or delays the development of clinical stage of the disease but does not eliminate MAP and is usually accompanied by interference with bovine tuberculosis diagnostics as well as local tissue damage. Subunit vaccines with well-defined antigens in combination...... vaccine with activation of protective immune response in experimentally challenged calves, with a focus on cell-mediated immune responses chiefly interferon gamma (IFN-γ) and polyfunctional T cells. The antigen composition of the vaccines was selected based on previous immunogenicity studies in cattle...

  3. A New Scientific Paradigm may be Needed to Finally Develop an HIV Vaccine.

    Science.gov (United States)

    Esparza, José

    2015-01-01

    The bulk of current HIV vaccine research is conducted within the infectious disease paradigm that has been very successful in developing vaccines against many other viral diseases. Different HIV vaccine concepts, based on the induction of neutralizing antibodies and/or cell mediated immunity, have been developed and clinically tested over the last 30 years, resulting in a few small successes and many disappointments. As new scientific knowledge is obtained, HIV vaccine concepts are constantly modified with the hope that the newly introduced tweaks (or paradigm drifts) will provide the solution to one of the most difficult challenges that modern biomedical research is confronting. Efficacy trials have been critical in guiding HIV vaccine development. However, from the five phase III efficacy trials conducted to date, only one (RV144) resulted in modest efficacy. The results from RV144 were surprising in many ways, including the identified putative correlates of protection (or risk), which did not include neutralizing antibodies or cytotoxic T-cells. The solution to the HIV vaccine challenge may very well come from approaches based on the current paradigm. However, at the same time, out-of-the-paradigm ideas should be systematically explored to complement the current efforts. New mechanisms are needed to identify and support the innovative research that will hopefully accelerate the development of an urgently needed HIV vaccine.

  4. Influence of potential protective mechanisms on the development of live rotavirus vaccines.

    Science.gov (United States)

    Ward, Richard L; Clark, H Fred; Offit, Paul A

    2010-09-01

    Rotaviruses cause extensive morbidity and mortality worldwide, thus corroborating the need for a vaccine that is effective in all socioeconomic environments. Vaccines evaluated in clinical trials have all been live attenuated rotaviruses that are delivered orally to mimic the excellent protection observed after natural infection. The mechanisms by which these vaccine candidates or wild-type rotaviruses elicit protection are not fully understood. During the 1980s, several candidate vaccines provided little protection, particularly in developing countries, and were discontinued. Two, however, are in the process of being licensed worldwide, and several others are undergoing clinical trials. Development of live rotavirus vaccines has been highly influenced by views regarding the importance of serotype-specific neutralizing antibody. Development of several candidate vaccines is based on the concept that neutralizing antibody is the primary determinant of protection. These candidates, including 1 of the 2 being licensed worldwide (RotaTeq), are composed of multiple rotavirus strains representative of the major human rotavirus serotypes. The other group of candidates has been developed based on the theory that protection is not solely dependent on neutralizing antibody. These candidates are composed of single rotavirus strains and include the other vaccine being licensed worldwide (Rotarix). Studies that provide the basis for each approach will be presented and discussed.

  5. Development of a new tuberculosis vaccine: is there value in the mucosal approach?

    Science.gov (United States)

    Diogo, Gil Reynolds; Reljic, Rajko

    2014-01-01

    TB is a global health problem, killing 1.5 million people every year. The only currently available vaccine, Mycobacterium bovis BCG, is effective against severe childhood forms, but it demonstrates a variable efficacy against the pulmonary form of TB in adults. Many of these adult TB cases result from the reactivation of an initially controlled, latent Mycobacterium tuberculosis infection. Effective prophylactic vaccination remains the key long-term strategy for combating TB. Continued belief in reaching this goal requires unrelenting innovation in the formulation and delivery of candidate vaccines. It is also based on the assumption, that the failure of recent human vaccine trials could have been due to a suboptimal vaccine design and delivery, and therefore should not erode the key principle that a TB vaccine is an attainable target. This report gives a brief overview of the mucosal immune system in the context of M. tuberculosis infection, and focuses on the most recent advances in the field of mucosal TB vaccine development, with a specific emphasis on subunit TB vaccines.

  6. Development of a national agreement on human papillomavirus vaccination in Japan: an infodemiology study.

    Science.gov (United States)

    Nakada, Haruka; Yuji, Koichiro; Tsubokura, Masaharu; Ohsawa, Yukio; Kami, Masahiro

    2014-05-15

    A national agreement on human papillomavirus (HPV) vaccination was achieved relatively quickly in Japan as compared to the United States and India. The objective was to identify the role of print and online media references, including references to celebrities or other informants, as factors potentially responsible for the relatively rapid national acceptance of HPV vaccination in Japan. A method of text mining was performed to select keywords, representing the context of the target documents, from articles relevant to the promotion of HPV vaccination appearing in major Japanese newspapers and Web pages between January 2009 and July 2010. The selected keywords were classified as positive, negative, or neutral, and the transition of the frequency of their appearance was analyzed. The number of positive and neutral keywords appearing in newspaper articles increased sharply in early 2010 while the number of negative keywords remained low. The numbers of positive, neutral, and negative keywords appearing in Web pages increased gradually and did not significantly differ by category. Neutral keywords, such as "vaccine" and "prevention," appeared more frequently in newspaper articles, whereas negative keywords, such as "infertility" and "side effect," appeared more frequently in Web pages. The extraction of the positive keyword "signature campaign" suggests that vaccine beneficiaries cooperated with providers in promoting HPV vaccination. The rapid development of a national agreement regarding HPV vaccination in Japan may be primarily attributed to the advocacy of vaccine beneficiaries, supported by advocacy by celebrities and positive reporting by print and online media.

  7. Engineering Foot-and-Mouth Disease Viruses with Improved Growth Properties for Vaccine Development

    Science.gov (United States)

    Zheng, Haixue; Guo, Jianhong; Jin, Ye; Yang, Fan; He, Jijun; Lv, Lv; Zhang, Kesan; Wu, Qiong; Liu, Xiangtao; Cai, Xuepeng

    2013-01-01

    Background No licensed vaccine is currently available against serotype A foot-and-mouth disease (FMD) in China, despite the isolation of A/WH/CHA/09 in 2009, partly because this strain does not replicate well in baby hamster kidney (BHK) cells. Methodology/Principal Findings A novel plasmid-based reverse genetics system was used to construct a chimeric strain by replacing the P1 gene in the vaccine strain O/CHA/99 with that from the epidemic stain A/WH/CHA/09. The chimeric virus displayed growth kinetics similar to those of O/CHA/99 and was selected for use as a candidate vaccine strain after 12 passages in BHK cells. Cattle were vaccinated with the inactivated vaccine and humoral immune responses were induced in most of the animals on day 7. A challenge infection with A/WH/CHA/09 on day 28 indicated that the group given a 4-µg dose was fully protected and neither developed viremia nor seroconverted to a 3ABC antigen. Conclusions/Significance Our data demonstrate that the chimeric virus not only propagates well in BHK cells and has excellent antigenic matching against serotype A FMD, but is also a potential marker vaccine to distinguish infection from vaccination. These results suggest that reverse genetics technology is a useful tool for engineering vaccines for the prevention and control of FMD. PMID:23372840

  8. Prospects for development of a rotavirus vaccine against rotavirus diarrhea in infants and young children.

    Science.gov (United States)

    Kapikian, A Z; Flores, J; Hoshino, Y; Midthun, K; Gorziglia, M; Green, K Y; Chanock, R M; Potash, L; Sears, S D; Clements, M L

    1989-01-01

    Major advances have been made in elucidating the etiologic agents of severe infantile diarrhea, and it is clear that rotaviruses are the single most important etiologic agents. Progress in the development of rotavirus vaccine candidates has also moved swiftly with the "Jennerian" approach, in which a related live, attenuated rotavirus strain from a nonhuman host is used as the immunizing antigen. If this strategy is not effective against all rotavirus serotypes, reassortant rotaviruses hold great promise for the development of a multivalent vaccine. Field trials with the "Jennerian" approach vaccines are under way, and phase 1 trials with the reassortants have been initiated.

  9. Should developing countries be testing grounds for vaccines rejected by the USA?

    Science.gov (United States)

    1994-01-01

    The World Health Organization (WHO) plans to start large scale trials of human immunodeficiency virus (HIV) vaccines in developing countries. It has been placed in a difficult position by the decision of the National Institutes of Health to postpone such trials in the US, a poor decision according to Genetech, owner of 1 of the vaccines. WHO will, however, carry out the trials in Brazil and Thailand in 1995. Some will ask if the people of developing countries should be used as guinea pigs; others will point to the urgency of the pandemic in areas of the Third World. Testing is cheaper and fewer ethical questions are asked in developing countries. But the vaccines, once tested, will be too expensive for these same countries to afford. A working vaccine for the US or western Europe provide a profit incentive for companies like Genetech; the same vaccines for developing countries do not. The decision by the National Institute of Allergy and Infectious Disease (NIAID, a component of NIH) to discontinue phase III trials changes the momentum of research on HIV vaccines by private companies. Genetech fears a repeat of its hepatitis B vaccine, which, at $1, is still too expensive for countries such as Uganda or Kenya. Vaccines developed to date have involved strains dominant in North America and Europe. These strains also occur in Latin America, the Caribbean, and some parts of Thailand; however, there have been no clinical trials of strains prevalent to Africa. Vaccines for Africa are unappealing to drug companies in terms of profit.

  10. Development of a competitive ELISA for NS3 antibodies as DIVA test accompanying the novel Disabled Infectious Single Animal (DISA) vaccine for bluetongue

    NARCIS (Netherlands)

    Tacken, M.G.J.; Daus, F.J.; Feenstra, F.; Gennip, van H.G.P.; Rijn, van P.A.

    2015-01-01

    Recently, we have developed a novel vaccine for Bluetongue named BT Disabled Infectious Single Animal (DISA) vaccine. Due to the lack of non-essential NS3/NS3a protein, BT DISA vaccine is a replicating vaccine, but without the inherent risks of live-attenuated vaccines, such as residual virulence or

  11. A fuzzy MICMAC analysis for improving supply chain performance of basic vaccines in developing countries.

    Science.gov (United States)

    Chandra, Dheeraj; Kumar, Dinesh

    2018-03-01

    In recent years, demand to improve child immunization coverage globally, and the development of the latest vaccines and technology has made the vaccine market very complex. The rise in such complexities often gives birth to numerous issues in the vaccine supply chain, which are the primary cause of its poor performance. Figuring out the cause of the performance problem can help you decide how to address it. The goal of the present study is to identify and analyze important issues in the supply chain of basic vaccines required for child immunization in the developing countries. Twenty-five key issues as various factors of the vaccine supply chain have been presented in this paper. Fuzzy MICMAC analysis has been carried out to classify the factors based on their driving and dependence power and to develop a hierarchy based model. Further, the findings have been discussed with the field experts to identify the critical factors. Three factors: better demand forecast, communication between the supply chain members, and proper planning and scheduling have been identified as the critical factors of vaccine supply chain. These factors should be given special care to improve vaccine supply chain performance.

  12. GAVI and the Vaccine Fund--a boon for immunization in the developing world.

    Science.gov (United States)

    Balaji, K A

    2004-01-01

    The Global Alliance for Vaccines and Immunization (GAVI) and The Vaccine Fund are two major global initiatives adopted with the objectives of improving access to immunization services particularly in the underdeveloped and developing countries and introduction of new but under-used vaccines in the developing countries in particular where these diseases are highly prevalent. GAVI is a collaborative mission that brings together governments in developing and industrialized countries, UNICEF, WHO, the World Bank, the Bill & Melinda Gates Foundation, vaccine manufacturers and all other stake holders to harness the strengths and experiences of multiple partners in immunization. The Vaccine Fund is a financing mechanism established to mobilize resources to serve the mission of GAVI. This article reviews the objectives, strategies, organization and the funding issues of this global initiative. In the Indian perspective, GAVI is presently playing a major role in introduction of Hepatitis-B vaccine for infants in India. The article outlined the pilot project currently being implemented by GoI and the future prospects of integrating Hepatitis-B vaccine and auto disable syringes into the routine immunization program as well as strengthening the routine immunization services when the government decides to expand the project.

  13. Advances in the development of enterohemorrhagic Escherichia coli vaccines using murine models of infection

    Science.gov (United States)

    Garcia-Angulo, Victor A.; Kalita, Anjana; Torres, Alfredo G.

    2013-01-01

    Enterohemorrhagic Escherichia coli (EHEC) strains are food borne pathogens with importance in public health. EHEC colonizes the large intestine and causes diarrhea, hemorrhagic colitis and in some cases, life-threatening hemolytic-uremic syndrome (HUS) due to the production of Shiga toxins (Stx). The lack of effective clinical treatment, sequelae after infection and mortality rate in humans supports the urgent need of prophylactic approaches, such as development of vaccines. Shedding from cattle, the main EHEC reservoir and considered the principal food contamination source, has prompted the development of licensed vaccines that reduce EHEC colonization in ruminants. Although murine models do not fully recapitulate human infection, they are commonly used to evaluate EHEC vaccines and the immune/protective responses elicited in the host. Mice susceptibility differs depending of the EHEC inoculums; therefore, displaying different mortality rates and Stx-mediated renal damage. Therefore, several experimental protocols have being pursued in this model to develop EHEC-specific vaccines. Recent candidate vaccines evaluated include those composed of virulence factors alone or as fused-subunits, DNA-based, attenuated bacteria and bacterial ghosts. In this review, we summarize progress in the design and testing of EHEC vaccines and the use of different strategies for the evaluation of novel EHEC vaccines in the murine model. PMID:23707170

  14. Development of replication-competent viral vectors for HIV vaccine delivery.

    Science.gov (United States)

    Parks, Christopher L; Picker, Louis J; King, C Richter

    2013-09-01

    To briefly describe some of the replication-competent vectors being investigated for development of candidate HIV vaccines focusing primarily on technologies that have advanced to testing in macaques or have entered clinical trials. Replication-competent viral vectors have advanced to the stage at which decisions can be made regarding the future development of HIV vaccines. The viruses being used as replication-competent vector platforms vary considerably, and their unique attributes make it possible to test multiple vaccine design concepts and also mimic various aspects of an HIV infection. Replication-competent viral vectors encoding simian immunodeficiency virus or HIV proteins can be used to safely immunize macaques, and in some cases, there is evidence of significant vaccine efficacy in challenge protection studies. Several live HIV vaccine vectors are in clinical trials to evaluate immunogenicity, safety, the effect of mucosal delivery, and potential effects of preexisting immunity. A variety of DNA and RNA viruses are being used to develop replication-competent viral vectors for HIV vaccine delivery. Multiple viral vector platforms have proven to be well tolerated and immunogenic with evidence of efficacy in macaques. Some of the more advanced HIV vaccine prototypes based on vesicular stomatitis virus, vaccinia virus, measles virus, and Sendai virus are in clinical trials.

  15. Overview of recent DNA vaccine development for fish

    Science.gov (United States)

    Kurath, G.; ,

    2005-01-01

    Since the first description of DNA vaccines for fish in 1996, numerous studies of genetic immunisation against the rhabdovirus pathogens infectious haematopoietic necrosis virus (IHNV) and viral haemorrhagic septicaemia virus (VHSV) have established their potential as both highly efficacious biologicals and useful basic research tools. Single small doses of rhabdovirus DNA constructs provide extremely strong protection against severe viral challenge under a variety of conditions. DNA vaccines for several other important fish viruses, bacteria, and parasites are under investigation, but they have not yet shown high efficacy. Therefore, current research is focussed on mechanistic studies to understand the basis of protection, and on improvement of the nucleic acid vaccine applications against a wider range of fish pathogens.

  16. Reaching international GMP standards for vaccine production: challenges for developing countries.

    Science.gov (United States)

    Milstien, Julie; Costa, Alejandro; Jadhav, Suresh; Dhere, Rajeev

    2009-05-01

    Standards for vaccine production have been increasing at a rapid rate. Current standards of good manufacturing practice (GMP) had been thought to be out of the reach of developing country vaccine producers, many of whom are in the public sector, overseen by unvalidated national regulatory authorities (NRAs). With the advent of the GMP regulations in 1963 and their application to vaccine production, even many industrialized country manufacturers with stringent NRA oversight had difficulties. This article assesses the ability of developing country manufacturers to meet GMP by the only currently available global indicator: WHO prequalification. As recently as 1996, no developing country NRA was considered able to enforce GMP compliance. That number increased to four in 2002 and six in 2006, with a concomitant increase in the number of manufacturers considered to be operating to GMP standards. Examples of the difficulties faced by manufacturers in achieving this are given, as well as implications for the future vaccine market.

  17. HPV as a model for the development of prophylactic and therapeutic cancer vaccines.

    Science.gov (United States)

    Samara, Raed N; Khleif, Samir N

    2009-08-01

    HPV has been linked to many human malignancies and, as such, represents a major public health crisis. The understanding of HPV biology, however, has helped tremendously in developing prophylactic vaccines, which should help in decreasing mortality due to HPV infections. Understanding HPV biology has allowed researchers to use the virus as a model for the development of not only prophylactic vaccines, but also therapeutic ones. The advantages of HPV as a model stem from the limited number of proteins encoded by the HPV genome that can be targeted by vaccines, and also from the restricted expression of certain viral proteins during different stages of infection. In this review, we discuss how HPV can be used as a model for the development of both prophylactic and therapeutic vaccines.

  18. Comparative study on three locally developed live orf virus vaccines for sheep in Saudi Arabia

    Directory of Open Access Journals (Sweden)

    Fahdel M. Housawi

    2012-02-01

    Full Text Available The epidemiology of orf virus infection in Saudi Arabia (SA has been researched since 1990. The results obtained during this period indicate that the disease is widespread, has great economic impact and that no vaccine has been used against it. The present study compares the immunogenicity and protective efficacy of three locally developed live orf virus vaccines. Two of them differ in their passage history in Vero cell culture and the third was used as a virulent virus in glycerine buffer. To the best of the authors’ knowledge, no similar comparative study has been conducted in the Middle East utilising three types of vaccines prepared from the same virus strain. Selection of the candidate seed orf virus and performance of the quality control tests were as laid out by the OIE for veterinary vaccine production. The vaccine seed virus was a field orf virus isolated from a previous orf outbreak in Saudi Arabia. A simple novel formula was developed to calculate the rate of reduction in the healing time (RHT % in the challenged sheep. This allowed direct comparison of the efficacy of the three types of vaccines employed in the present study. The efficacy of each vaccine was tested on a cohort of local Noemi sheep.

  19. Enhancing the role of veterinary vaccines reducing zoonotic diseases of humans: Linking systems biology with vaccine development

    Energy Technology Data Exchange (ETDEWEB)

    Adams, Leslie G.; Khare, Sangeeta; Lawhon, Sara D.; Rossetti, Carlos A.; Lewin, Harris A.; Lipton, Mary S.; Turse, Joshua E.; Wylie, Dennis C.; Bai, Yu; Drake, Kenneth L.

    2011-09-22

    The aim of research on infectious diseases is their prevention, and brucellosis and salmonellosis as such are classic examples of worldwide zoonoses for application of a systems biology approach for enhanced rational vaccine development. When used optimally, vaccines prevent disease manifestations, reduce transmission of disease, decrease the need for pharmaceutical intervention, and improve the health and welfare of animals, as well as indirectly protecting against zoonotic diseases of people. Advances in the last decade or so using comprehensive systems biology approaches linking genomics, proteomics, bioinformatics, and biotechnology with immunology, pathogenesis and vaccine formulation and delivery are expected to enable enhanced approaches to vaccine development. The goal of this paper is to evaluate the role of computational systems biology analysis of host:pathogen interactions (the interactome) as a tool for enhanced rational design of vaccines. Systems biology is bringing a new, more robust approach to veterinary vaccine design based upon a deeper understanding of the host pathogen interactions and its impact on the host's molecular network of the immune system. A computational systems biology method was utilized to create interactome models of the host responses to Brucella melitensis (BMEL), Mycobacterium avium paratuberculosis (MAP), Salmonella enterica Typhimurium (STM), and a Salmonella mutant (isogenic *sipA, sopABDE2) and linked to the basis for rational development of vaccines for brucellosis and salmonellosis as reviewed by Adams et al. and Ficht et al. [1,2]. A bovine ligated ileal loop biological model was established to capture the host gene expression response at multiple time points post infection. New methods based on Dynamic Bayesian Network (DBN) machine learning were employed to conduct a comparative pathogenicity analysis of 219 signaling and metabolic pathways and 1620 gene ontology (GO) categories that defined the host

  20. Pre-clinical toxicology considerations for vaccine development.

    Science.gov (United States)

    Al-Humadi, Nabil

    2017-10-13

    Vaccine development requires pre-clinical toxicology studies, following good laboratory practice (GLP), before first in human (phase I) use. Many factors are critical in the final outcome of any pre-clinical toxicology study. The study design is one of these critical factors and should be carefully planned to avoid any false negative and/or false positive results. Preparation is another most critical factor in a successful study. Major changes in any procedure during the course of study should be avoided by all means. For example, if the protocol specified the tail as the site of blood collection and this procedure was used for the control group at the day of necropsy, this collection site should never be replaced by another site (e.g. foot, eye, or heart) in all other treatment groups. Food restrictions and acute restraint stress affect clinical pathology data and should be avoided in rodents. Institutional Animal Care and Use Committee (IACUC) guidelines for frequent blood collections (weekly, monthly, or at necropsy) in any animal species should be strictly followed. Clinical pathology data will be profoundly affected by any diversion from the recommended volumes. If CO2 is specified in the protocol for anesthesia and/or euthanasia, ensuring enough quantity to use for all groups at necropsy is a very important factor. Using two different anesthetics in any study (e.g. CO2 vs. pentobarbital) may result in false positive or false negative results in clinical chemistry parameters. Quality assurance elements (SOPs, instrument validation, lab certification etc.) affect the data interpretation and the final outcome of any toxicology study. SOPs should be up to date and written clearly. All lab instruments should be validated and all laboratories should be certified. Published by Elsevier Ltd.

  1. Development of next-generation respiratory virus vaccines through targeted modifications to viral immunomodulatory genes

    Science.gov (United States)

    Stobart, Christopher C.; Moore, Martin L.

    2016-01-01

    Vaccines represent one of the greatest contributions of the scientific community to global health. Yet, many pathogens remain either unchallenged or inadequately hindered by commercially available vaccines. Respiratory viruses pose distinct and difficult challenges due to their ability to rapidly spread, adapt, and modify the host immune response. Considerable research has been directed to understand the role of respiratory virus immunomodulatory proteins and how they influence the host immune response. We review here efforts to develop next-generation vaccines through targeting these key immunomodulatory genes in influenza virus, coronaviruses, respiratory syncytial virus, measles virus, and mumps virus. PMID:26434947

  2. Recent advances in vaccine development for herpes simplex virus types I and II.

    Science.gov (United States)

    Coleman, Jeffrey L; Shukla, Deepak

    2013-04-01

    Despite recent advances in vaccine design and strategies, latent infection with herpes simplex virus (HSV) remains a formidable challenge. Approaches involving live-attenuated viruses and inactivated viral preparations were popular throughout the twentieth century. In the past ten years, many vaccine types, both prophylactic or therapeutic, have contained a replication-defective HSV, viral DNA or glycoproteins. New research focused on the mechanism of immune evasion by the virus has involved developing vaccines with various gene deletions and manipulations combined with the use of new and more specific adjuvants. In addition, new "prime-boost" methods of strengthening the vaccine efficacy have proven effective, but there have also been flaws with some recent strategies that appear to have compromised vaccine efficacy in humans. Given the complicated lifecycle of HSV and its unique way of spreading from cell-to-cell, it can be concluded that the development of an ideal vaccine needs new focus on cell-mediated immunity, better understanding of the latent viral genome and serious consideration of gender-based differences in immunity development among humans. This review summarizes recent developments made in the field and sheds light on some potentially new ways to conquer the problem including development of dual-action prophylactic microbicides that prohibit viral entry and, in addition, induce a strong antigen response.

  3. New insights on the development of fungal vaccines: from immunity to recent challenges

    Directory of Open Access Journals (Sweden)

    Natasha P Medici

    2015-01-01

    Full Text Available Fungal infections are emerging as a major problem in part due to high mortality associated with systemic infections, especially in the case of immunocompromised patients. With the development of new treatments for diseases such as cancer and the acquired immune deficiency syndrome pandemic, the number of immunosuppressed patients has increased and, as a consequence, also the number of invasive fungal infections has increased. Several studies have proposed new strategies for the development of effective fungal vaccines. In addition, better understanding of how the immune system works against fungal pathogens has improved the further development of these new vaccination strategies. As a result, some fungal vaccines have advanced through clinical trials. However, there are still many challenges that prevent the clinical development of fungal vaccines that can efficiently immunise subjects at risk of developing invasive fungal infections. In this review, we will discuss these new vaccination strategies and the challenges that they present. In the future with proper investments, fungal vaccines may soon become a reality.

  4. Recent advances in the development of vaccines for Ebola virus disease.

    Science.gov (United States)

    Ohimain, Elijah Ige

    2016-01-04

    Ebola virus is one of the most dangerous microorganisms in the world causing hemorrhagic fevers in humans and non-human primates. Ebola virus (EBOV) is a zoonotic infection, which emerges and re-emerges in human populations. The 2014 outbreak was caused by the Zaire strain, which has a kill rate of up to 90%, though 40% was recorded in the current outbreak. The 2014 outbreak is larger than all 20 outbreaks that have occurred since 1976, when the virus was first discovered. It is the first time that the virus was sustained in urban centers and spread beyond Africa into Europe and USA. Thus far, over 22,000 cases have been reported with about 50% mortality in one year. There are currently no approved therapeutics and preventive vaccines against Ebola virus disease (EVD). Responding to the devastating effe1cts of the 2014 outbreak and the potential risk of global spread, has spurred research for the development of therapeutics and vaccines. This review is therefore aimed at presenting the progress of vaccine development. Results showed that conventional inactivated vaccines produced from EBOV by heat, formalin or gamma irradiation appear to be ineffective. However, novel vaccines production techniques have emerged leading to the production of candidate vaccines that have been demonstrated to be effective in preclinical trials using small animal and non-human primates (NHP) models. Some of the promising vaccines have undergone phase 1 clinical trials, which demonstrated their safety and immunogenicity. Many of the candidate vaccines are vector based such as Vesicular Stomatitis Virus (VSV), Rabies Virus (RABV), Adenovirus (Ad), Modified Vaccinia Ankara (MVA), Cytomegalovirus (CMV), human parainfluenza virus type 3 (HPIV3) and Venezuelan Equine Encephalitis Virus (VEEV). Other platforms include virus like particle (VLP), DNA and subunit vaccines. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Development of Modified Vaccinia Virus Ankara-based Influenza Vaccines

    NARCIS (Netherlands)

    A.F. Altenburg (Arwen)

    2018-01-01

    textabstractInfluenza viruses continuously circulate in the human population and are estimated to cause 3-5 million cases of severe respiratory illness annually worldwide of which 250.000-500.000 have a fatal outcome. Vaccination is the most efficient measure to control infectious diseases,

  6. Development of a novel vaccine for contagious caprine ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    ... grow efficiently, express protective Mccp antigens, and be used either as a live or inactivated vaccine. This 24-month project is a collaboration between the University of Bern in Switzerland, the Institut national de la recherche agronomique at the University of Bordeaux, France, and the J. Craig Venter Institute in the USA.

  7. Development of a Subunit Vaccine for Contagious Bovine ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    2017-08-11

    This project will allow researchers from Canada and Kenya to field trial a vaccine for contagious bovine pleuropneumonia. ... Researchers and practitioners gathered in Montreal on August 11, 2017 to discuss the potential of child care to benefit women through improved economic opportunities and empowerment as part of ...

  8. Experimental human challenge infections can accelerate clinical malaria vaccine development

    NARCIS (Netherlands)

    Sauerwein, R.W.; Roestenberg, M.; Moorthy, V.S.

    2011-01-01

    Malaria is one of the most frequently occurring infectious diseases worldwide, with almost 1 million deaths and an estimated 243 million clinical cases annually. Several candidate malaria vaccines have reached Phase IIb clinical trials, but results have often been disappointing. As an alternative to

  9. Efficacy of Killed Adjuvanted FMD Vaccine Developed with ...

    African Journals Online (AJOL)

    In this study the potency of killed Foot and Mouth Disease (FMD) vaccines serotypes SAT1 (Nig 1/98) and SAT 2 (Nig 2/97) virus isolates, formulated with montanide ISA 206 adjuvant was determined in guinea pigs and cattle by antibody assay using Complement Fixation and Serum Neutralization tests. The antibody titres ...

  10. Towards a preventive strategy for neosporosis: challenges and future perspectives for vaccine development against infection with Neospora caninum.

    Science.gov (United States)

    Nishikawa, Yoshifumi

    2017-08-10

    Neosporosis is caused by the intracellular protozoan parasite Neospora caninum. This major disease-causing pathogen is responsible for inducing abortion in cattle, and these adverse events occur sporadically all over the world, including Japan. Currently, there are no vaccines on the market against infection with N. caninum. Because live and attenuated vaccines against N. caninum have had safety and effectiveness issues, development of a next-generation vaccine is urgently required. To develop a vaccine against neosporosis, my laboratory has been focused on the following: 1) understanding the host immune responses against Neospora infection, 2) identifying vaccine antigens and 3) developing an effective antigen-delivery system. The research strategy taken in my laboratory will have strong potential to progress current understanding of the pathogenesis of N. caninum infection and promote development of a novel subunit vaccine based on the specific vaccine antigen with an antigen-delivery system for controlling neosporosis.

  11. Advances in neglected tropical disease vaccines: Developing relative potency and functional assays for the Na-GST-1/Alhydrogel hookworm vaccine.

    Science.gov (United States)

    Brelsford, Jill B; Plieskatt, Jordan L; Yakovleva, Anna; Jariwala, Amar; Keegan, Brian P; Peng, Jin; Xia, Pengjun; Li, Guangzhao; Campbell, Doreen; Periago, Maria Victoria; Correa-Oliveira, Rodrigo; Bottazzi, Maria Elena; Hotez, Peter J; Diemert, David; Bethony, Jeffrey M

    2017-02-01

    A new generation of vaccines for the neglected tropical diseases (NTDs) have now advanced into clinical development, with the Na-GST-1/Alhydrogel Hookworm Vaccine already being tested in Phase 1 studies in healthy adults. The current manuscript focuses on the often overlooked critical aspects of NTD vaccine product development, more specifically, vaccine stability testing programs. A key measure of vaccine stability testing is "relative potency" or the immunogenicity of the vaccine during storage. As with most NTD vaccines, the Na-GST-1/Alhydrogel Hookworm Vaccine was not developed by attenuation or inactivation of the pathogen (Necator americanus), so conventional methods for measuring relative potency are not relevant for this investigational product. Herein, we describe a novel relative potency testing program and report for the first time on the clinical lot of this NTD vaccine during its first 60 months of storage at 2-8°C. We also describe the development of a complementary functional assay that measures the ability of IgG from animals or humans immunized with Na-GST-1/Alhydrogel to neutralize this important hookworm enzyme. While 90% inhibition of the catalytic activity of Na-GST-1 was achieved in animals immunized with Na-GST-1/Alhydrogel, lower levels of inhibition were observed in immunized humans. Moreover, anti-Na-GST-1 antibodies from volunteers in non-hookworm endemic areas were better able to inhibit catalytic activity than anti-Na-GST-1 antibodies from volunteers resident in hookworm endemic areas. The results described herein provide the critical tools for the product development of NTD vaccines.

  12. Dendritic cell-targeting DNA-based mucosal adjuvants for the development of mucosal vaccines

    Science.gov (United States)

    Kataoka, Kosuke; Fujihashi, Kohtaro

    2009-01-01

    In order to establish effective mucosal immunity against various mucosal pathogens, vaccines must be delivered via the mucosal route and contain effective adjuvant(s). Since mucosal adjuvants can simply mix with the antigen, it is relatively easy to adapt them for different types of vaccine development. Even in simple admixture vaccines, the adjuvant itself must be prepared without any complications. Thus, CpG oligodeoxynucleotides or plasmids encoding certain cDNA(s) would be potent mucosal adjuvant candidates when compared with other substances that can be used as mucosal adjuvants. The strategy of a DNA-based mucosal adjuvant facilitates the targeting of mucosal dendritic cells, and thus is an effective and safe approach. It would also provide great flexibility for the development of effective vaccines for various mucosal pathogens. PMID:19722892

  13. Development of a vaccine to prevent Japanese encephalitis: a brief review

    Science.gov (United States)

    Wiwanitkit, Viroj

    2009-01-01

    Japanese encephalitis (ICD 10: A83.0) is an important specific viral encephalitis caused by the Japanese encephalitis virus, a virus of the Flavivirus group. Millions of people, especially those in endemic areas of developing countries in Asia, are at high risk from this infection. Therefore proper management to deal with this virus is essential. There is no specific treatment for Japanese encephalitis virus. Supportive and symptomatic treatments are usually used, which emphasize the importance of prevention in this specific neurological disorder. Vector control or vaccination can be used to prevent the disease. Because the existing Japanese encephalitis vaccine poses some undesirable problems, a new vaccine is needed. The process of developing a new vaccine is briefly discussed. PMID:20360904

  14. Receptor-binding domain as a target for developing SARS vaccines.

    Science.gov (United States)

    Zhu, Xiaojie; Liu, Qi; Du, Lanying; Lu, Lu; Jiang, Shibo

    2013-08-01

    A decade ago, severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) caused a global pandemic with a mortality rate of 10%. Reports of recent outbreaks of a SARS-like disease caused by Middle East respiratory syndrome coronavirus (MERS-CoV) have raised serious concerns of a possible reemergence of SARS-CoV, either by laboratory escape or the presence of a natural reservoir. Therefore, the development of effective and safe SARS vaccines is still needed. Based on our previous studies, we believe that the receptor-binding domain (RBD) in the S1 subunit of the SARS-CoV spike (S) protein is the most important target for developing a SARS vaccine. In particular, RBD of S protein contains the critical neutralizing domain (CND), which is able to induce highly potent neutralizing antibody response and cross-protection against divergent SARS-CoV strains. Furthermore, a RBD-based subunit vaccine is expected to be safer than other vaccines that may induce Th2-type immunopathology. This review will discuss key advances in the development of RBD-based SARS vaccines and the possibility of using a similar strategy to develop vaccines against MERS-CoV.

  15. Development of an inactivated iridovirus vaccine against turbot viral reddish body syndrome

    Science.gov (United States)

    Fan, Tingjun; Hu, Xiuzhong; Wang, Liyan; Geng, Xiaofen; Jiang, Guojian; Yang, Xiuxia; Yu, Miaomiao

    2012-03-01

    Turbot ( Scophthalmus maximus L.) reddish body iridovirus (TRBIV) was propagated in turbot fin cells (TF cells) and inactivated as the TRBIV vaccine with its protection efficiency evaluated in this study. TF cells were cultured in 10% bovine calf serum (BCS)-containing MEM medium (pH7.0) at 22°C, in which TRBIV propagated to a titer as high as 105.6 TCID50 mL-1. The TRBIV was inactivated with 0.1% formalin and formulated with 0.5% aluminum hydroxide. The inactivated vaccine caused neither cytopathogenic effect (CPE) on TF cells nor pathogenic effect on turbots. After being administered with the vaccine twice via muscle injection, the turbot developed high-tittered TRBIV neutralizing antibodies in a dose-dependent manner. The vaccine protected the turbot from dying with an immunoprotection rate of 83.3% as was determined via subcutaneous vaccination in the laboratory and 90.5% via bath vaccination in turbot farms, respectively. The inactivated vaccine was very immunogenic, efficiently preventing turbot from death. It holds the potential of being applied in aquaculture.

  16. The Ebola Vaccine Team B: a model for promoting the rapid development of medical countermeasures for emerging infectious disease threats.

    Science.gov (United States)

    Osterholm, Michael; Moore, Kristine; Ostrowsky, Julie; Kimball-Baker, Kathleen; Farrar, Jeremy

    2016-01-01

    In support of accelerated development of Ebola vaccines from preclinical research to clinical trials, in November, 2014, the Wellcome Trust and the Center for Infectious Disease Research and Policy (CIDRAP) at the University of Minnesota established the Wellcome Trust-CIDRAP Ebola Vaccine Team B initiative. This ongoing initiative includes experts with global experience in various phases of bringing new vaccines to market, such as funding, research and development, manufacturing, determination of safety and efficacy, regulatory approval, and vaccination delivery. It also includes experts in community engagement strategies and ethical issues germane to vaccination policies, including eight African scientists with direct experience in developing and implementing vaccination policies in Africa. Ebola Vaccine Team B members have worked on a range of vaccination programmes, such as polio eradication (Africa and globally), development of meningococcal A disease vaccination campaigns in Africa, and malaria and HIV/AIDS vaccine research. We also provide perspective on how this experience can inform future situations where urgent development of vaccines is needed, and we comment on the role that an independent, expert group such as Team B can have in support of national and international public health authorities toward addressing a public health crisis. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. The development of vaccines: how the past led to the future.

    Science.gov (United States)

    Plotkin, Stanley A; Plotkin, Susan L

    2011-10-03

    The history of vaccine development has seen many accomplishments, but there are still many diseases that are difficult to target, and new technologies are being brought to bear on them. Past successes have been largely due to elicitation of protective antibodies based on predictions made from the study of animal models, natural infections and seroepidemiology. Those predictions have often been correct, as indicated by the decline of many infections for which vaccines have been made over the past 200 years.

  18. RTS,S malaria vaccine development: progress and considerations for postapproval introduction

    OpenAIRE

    Asante KP; Adjei G; Enuameh Y; Owusu-Agyei S

    2016-01-01

    Kwaku Poku Asante, George Adjei, Yeetey Enuameh, Seth Owusu-Agyei Kintampo Health Research Centre, Kintampo, Brong Ahafo Region, Ghana Abstract: Though the burden of malaria has decreased in the last decade in some sub-Saharan African countries, it is still high in others, and there is no malaria vaccine in use. The development of malaria vaccines in combination with current control programs could be effective in reducing the malaria burden. In this paper, we review and discuss the progress ...

  19. Modeling the public health impact of malaria vaccines for developers and policymakers.

    Science.gov (United States)

    Nunes, Julia K; Cárdenas, Vicky; Loucq, Christian; Maire, Nicolas; Smith, Thomas; Shaffer, Craig; Måseide, Kårstein; Brooks, Alan

    2013-07-01

    Efforts to develop malaria vaccines show promise. Mathematical model-based estimates of the potential demand, public health impact, and cost and financing requirements can be used to inform investment and adoption decisions by vaccine developers and policymakers on the use of malaria vaccines as complements to existing interventions. However, the complexity of such models may make their outputs inaccessible to non-modeling specialists. This paper describes a Malaria Vaccine Model (MVM) developed to address the specific needs of developers and policymakers, who need to access sophisticated modeling results and to test various scenarios in a user-friendly interface. The model's functionality is demonstrated through a hypothetical vaccine. The MVM has three modules: supply and demand forecast; public health impact; and implementation cost and financing requirements. These modules include pre-entered reference data and also allow for user-defined inputs. The model includes an integrated sensitivity analysis function. Model functionality was demonstrated by estimating the public health impact of a hypothetical pre-erythrocytic malaria vaccine with 85% efficacy against uncomplicated disease and a vaccine efficacy decay rate of four years, based on internationally-established targets. Demand for this hypothetical vaccine was estimated based on historical vaccine implementation rates for routine infant immunization in 40 African countries over a 10-year period. Assumed purchase price was $5 per dose and injection equipment and delivery costs were $0.40 per dose. The model projects the number of doses needed, uncomplicated and severe cases averted, deaths and disability-adjusted life years (DALYs) averted, and cost to avert each. In the demonstration scenario, based on a projected demand of 532 million doses, the MVM estimated that 150 million uncomplicated cases of malaria and 1.1 million deaths would be averted over 10 years. This is equivalent to 943 uncomplicated cases

  20. Cost-effectiveness of introducing a rotavirus vaccine in developing countries: The case of Mexico

    Directory of Open Access Journals (Sweden)

    Gutierrez Juan-Pablo

    2008-07-01

    Full Text Available Abstract Background In developing countries rotavirus is the leading cause of severe diarrhoea and diarrhoeal deaths in children under 5. Vaccination could greatly alleviate that burden, but in Mexico as in most low- and middle-income countries the decision to add rotavirus vaccine to the national immunisation program will depend heavily on its cost-effectiveness and affordability. The objective of this study was to assess the cost-effectiveness of including the pentavalent rotavirus vaccine in Mexico's national immunisation program. Methods A cost-effectiveness model was developed from the perspective of the health system, modelling the vaccination of a hypothetical birth cohort of 2 million children monitored from birth through 60 months of age. It compares the cost and disease burden of rotavirus in an unvaccinated cohort of children with one vaccinated as recommended at 2, 4, and 6 months. Results Including the pentavalent vaccine in the national immunisation program could prevent 71,464 medical visits (59%, 5,040 hospital admissions (66%, and 612 deaths from rotavirus gastroenteritis (70%. At US$10 per dose and a cost of administration of US$13.70 per 3-dose regimen, vaccination would cost US$122,058 per death prevented, US$4,383 per discounted life-year saved, at a total net cost of US$74.7 million dollars to the health care system. Key variables influencing the results were, in order of importance, case fatality, vaccine price, vaccine efficacy, serotype prevalence, and annual loss of efficacy. The results are also very sensitive to the discount rate assumed when calculated per life-year saved. Conclusion At prices below US $15 per dose, the cost per life-year saved is estimated to be lower than one GNP per capita and hence highly cost effective by the WHO Commission on Macroeconomics and Health criteria. The cost-effectiveness estimates are highly dependent upon the mortality in the absence of the vaccine, which suggests that the vaccine

  1. User-Centered Design for Developing Interventions to Improve Clinician Recommendation of Human Papillomavirus Vaccination.

    Science.gov (United States)

    Henninger, Michelle L; Mcmullen, Carmit K; Firemark, Alison J; Naleway, Allison L; Henrikson, Nora B; Turcotte, Joseph A

    2017-01-01

    Human papillomavirus (HPV) is the most common sexually transmitted infection in the US and is associated with multiple types of cancer. Although effective HPV vaccines have been available since 2006, coverage rates in the US remain much lower than with other adolescent vaccinations. Prior research has shown that a strong recommendation from a clinician is a critical determinant in HPV vaccine uptake and coverage. However, few published studies to date have specifically addressed the issue of helping clinicians communicate more effectively with their patients about the HPV vaccine. To develop one or more novel interventions for helping clinicians make strong and effective recommendations for HPV vaccination. Using principles of user-centered design, we conducted qualitative interviews, interviews with persons from analogous industries, and a data synthesis workshop with multiple stakeholders. Five potential intervention strategies targeted at health care clinicians, youth, and their parents were developed. The two most popular choices to pursue were a values-based communication strategy and a puberty education workbook. User-centered design is a useful strategy for developing potential interventions to improve the rate and success of clinicians recommending the HPV vaccine. Further research is needed to test the effectiveness and acceptability of these interventions in clinical settings.

  2. Analysis and genetic manipulation of Shigella virulence determinants for vaccine development.

    Science.gov (United States)

    Mills, S D; Sekizaki, T; Gonzalez-Carrero, M I; Timmis, K N

    1988-04-01

    Shigellosis is a major public health problem in developing countries. Current epidemics of Shigella dysenteriae serotype 1 strains are particularly serious and are characterized by high mortality rates. A high proportion of the isolates are resistant to many of the antibiotics currently in use in these countries, a feature which seriously compromises clinical treatment of the infections. Efficacious vaccines are thus urgently needed. Basic studies on Shigella virulence factors, infections in laboratory models, and host responses has led to the development of several strategies for the production of vaccines. All of these are live oral vaccines involving bacteria capable of at least limited survival in the animal intestine and of carrying selected antigens to the mucosal immune system. One type of vaccine involves non-pathogenic shigellae, attenuated either by introduction of a requirement for aromatic amino acids (aroD) or by loss of the large plasmid that specifies bacterial invasion of the mucosal epithelium. S. dysenteriae 1 strains under development as vaccines need to be engineered to eliminate high level Shiga toxin production, and a rapid and effective method to achieve this was recently elaborated. The second type of vaccine is represented by hybrid strains consisting of a carrier organism, such as an attenuated Salmonella or an Escherichia coli K-12 strain carrying the Shigella invasion plasmid, and the selected foreign antigen that it produces, in all cases so far the Shigella O antigen polysaccharide.

  3. Modified Vaccinia Virus Ankara: History, Value in Basic Research, and Current Perspectives for Vaccine Development.

    Science.gov (United States)

    Volz, A; Sutter, G

    2017-01-01

    Safety tested Modified Vaccinia virus Ankara (MVA) is licensed as third-generation vaccine against smallpox and serves as a potent vector system for development of new candidate vaccines against infectious diseases and cancer. Historically, MVA was developed by serial tissue culture passage in primary chicken cells of vaccinia virus strain Ankara, and clinically used to avoid the undesirable side effects of conventional smallpox vaccination. Adapted to growth in avian cells MVA lost the ability to replicate in mammalian hosts and lacks many of the genes orthopoxviruses use to conquer their host (cell) environment. As a biologically well-characterized mutant virus, MVA facilitates fundamental research to elucidate the functions of poxvirus host-interaction factors. As extremely safe viral vectors MVA vaccines have been found immunogenic and protective in various preclinical infection models. Multiple recombinant MVA currently undergo clinical testing for vaccination against human immunodeficiency viruses, Mycobacterium tuberculosis or Plasmodium falciparum. The versatility of the MVA vector vaccine platform is readily demonstrated by the swift development of experimental vaccines for immunization against emerging infections such as the Middle East Respiratory Syndrome. Recent advances include promising results from the clinical testing of recombinant MVA-producing antigens of highly pathogenic avian influenza virus H5N1 or Ebola virus. This review summarizes our current knowledge about MVA as a unique strain of vaccinia virus, and discusses the prospects of exploiting this virus as research tool in poxvirus biology or as safe viral vector vaccine to challenge existing and future bottlenecks in vaccinology. © 2017 Elsevier Inc. All rights reserved.

  4. Development of a Multivalent Subunit Vaccine against Tularemia Using Tobacco Mosaic Virus (TMV Based Delivery System.

    Directory of Open Access Journals (Sweden)

    Sukalyani Banik

    Full Text Available Francisella tularensis is a facultative intracellular pathogen, and is the causative agent of a fatal human disease known as tularemia. F. tularensis is classified as a Category A Biothreat agent by the CDC based on its use in bioweapon programs by several countries in the past and its potential to be used as an agent of bioterrorism. No licensed vaccine is currently available for prevention of tularemia. In this study, we used a novel approach for development of a multivalent subunit vaccine against tularemia by using an efficient tobacco mosaic virus (TMV based delivery platform. The multivalent subunit vaccine was formulated to contain a combination of F. tularensis protective antigens: OmpA-like protein (OmpA, chaperone protein DnaK and lipoprotein Tul4 from the highly virulent F. tularensis SchuS4 strain. Two different vaccine formulations and immunization schedules were used. The immunized mice were challenged with lethal (10xLD100 doses of F. tularensis LVS on day 28 of the primary immunization and observed daily for morbidity and mortality. Results from this study demonstrate that TMV can be used as a carrier for effective delivery of multiple F. tularensis antigens. TMV-conjugate vaccine formulations are safe and multiple doses can be administered without causing any adverse reactions in immunized mice. Immunization with TMV-conjugated F. tularensis proteins induced a strong humoral immune response and protected mice against respiratory challenges with very high doses of F. tularensis LVS. This study provides a proof-of-concept that TMV can serve as a suitable platform for simultaneous delivery of multiple protective antigens of F. tularensis. Refinement of vaccine formulations coupled with TMV-targeting strategies developed in this study will provide a platform for development of an effective tularemia subunit vaccine as well as a vaccination approach that may broadly be applicable to many other bacterial pathogens.

  5. Attenuation mechanism of Brucella melitensis M5-10, implications for vaccine development and differential diagnosis

    Directory of Open Access Journals (Sweden)

    Yuanqiang ZHENG,Yanchun SHI,Chang AN,Ruisheng LI,Dongjun LIU,Yuehua KE,Kairong MAO,Mingjuan YANG,Zeliang CHEN,Shorgan BOU

    2014-12-01

    Full Text Available Brucellosis is a worldwide zoonosis. Vaccination is the most efficient means to prevent and control brucellosis. The current licensed attenuated vaccines for animal use were developed by sequential passage in non-natural hosts that decreased virulence in its original hosts. The attenuation mechanism of these strains remains largely unknown. In the present study, we sequenced the genome of Brucella melitensis vaccine strain M5-10. Sequence analysis showed that a large number of genetic changes occurred in the vaccine strains. A total of 2854 genetic polymorphic sites, including 2548 SNP, 241 INDEL and 65 MNV were identified. Of the 2074 SNPs in coding regions, 1310 (63.2% were non-synonymous SNPs. Gene number, percent and N/S ratios were disproportionally distributed among the cog categories. Genetic polymorphic sites were identified in genes of the virB operon, flagella synthesis, and virulence regulating systems. These data indicate that changes in some cog categories and virulence genes might result in the attenuation. These attenuation mechanisms also have implications for screening and development of new vaccine strains. The genetic changes in the genome represent candidate sites for differential diagnosis between these vaccine strains and other virulence ones. Transcription analysis of virulence genes showed that expression of dnaK, vjbR were reduced in M5-10 strain when compared with that in 16M. A duplex PCR targeting virB6 and dnaK was successfully used to differentiate between M5-10 and the virulent 16M strain. The genome re-sequencing technique represents a strong strategy not only for evaluation of vaccines, but also for development of new vaccines.

  6. Development of live attenuated influenza vaccines against pandemic influenza strains.

    Science.gov (United States)

    Coelingh, Kathleen L; Luke, Catherine J; Jin, Hong; Talaat, Kawsar R

    2014-07-01

    Avian and animal influenza viruses can sporadically transmit to humans, causing outbreaks of varying severity. In some cases, further human-to-human virus transmission does not occur, and the outbreak in humans is limited. In other cases, sustained human-to-human transmission occurs, resulting in worldwide influenza pandemics. Preparation for future pandemics is an important global public health goal. A key objective of preparedness is to gain an understanding of how to design, test, and manufacture effective vaccines that could be stockpiled for use in a pandemic. This review summarizes results of an ongoing collaboration to produce, characterize, and clinically test a library of live attenuated influenza vaccine strains (based on Ann Arbor attenuated Type A strain) containing protective antigens from influenza viruses considered to be of high pandemic potential.

  7. Development of Cytomegalovirus-Based Vaccines Against Melanoma

    Science.gov (United States)

    2016-10-01

    cells are crucial in the defense against cancer, thus vaccination aimed at generating a large number of functional effector and memory CD8 T cells...annually. Because C. difficile forms spores that are extremely difficult to remove from institutional settings such as hospitals and nursing homes, a...the intradermal model were also disseminated in a research poster at the National MD/PhD Student Conference in July 2015. What do you plan to do

  8. Tocotrienols are good adjuvants for developing cancer vaccines

    Directory of Open Access Journals (Sweden)

    Radhakrishnan Ammu

    2010-01-01

    Full Text Available Abstract Background Dendritic cells (DCs have the potential for cancer immunotherapy due to their ability to process and present antigens to T-cells and also in stimulating immune responses. However, DC-based vaccines have only exhibited minimal effectiveness against established tumours in mice and humans. The use of appropriate adjuvant enhances the efficacy of DC based cancer vaccines in treating tumours. Methods In this study we have used tocotrienol-rich fraction (TRF, a non-toxic natural compound, as an adjuvant to enhance the effectiveness of DC vaccines in treating mouse mammary cancers. In the mouse model, six-week-old female BALB/c mice were injected subcutaneously with DC and supplemented with oral TRF daily (DC+TRF and DC pulsed with tumour lysate from 4T1 cells (DC+TL. Experimental mice were also injected with DC pulsed with tumour lysate and supplemented daily with oral TRF (DC+TL+TRF while two groups of animal which were supplemented daily with carrier oil (control and with TRF (TRF. After three times vaccination, mice were inoculated with 4T1 cells in the mammary breast pad to induce tumour. Results Our study showed that TRF in combination with DC pulsed with tumour lysate (DC+TL+TRF injected subcutaneously significantly inhibited the growth of 4T1 mammary tumour cells as compared to control group. Analysis of cytokines production from murine splenocytes showed significant increased productions of IFN-γ and IL-12 in experimental mice (DC+TL+TRF compared to control, mice injected with DC without TRF, mice injected with DC pulsed with tumour lysate and mice supplemented with TRF alone. Higher numbers of cytotoxic T cells (CD8 and natural killer cells (NK were observed in the peripheral blood of TRF adjuvanted DC pulsed tumour lysate mice. Conclusion Our study show that TRF has the potential to be an adjuvant to augment DC based immunotherapy.

  9. Development of a RVFV ELISA that can distinguish infected from vaccinated animals

    Directory of Open Access Journals (Sweden)

    Albariño César G

    2009-08-01

    Full Text Available Abstract Background Rift Valley Fever Virus is a pathogen of humans and livestock that causes significant morbidity and mortality throughout Africa and the Middle East. A vaccine that would protect animals from disease would be very beneficial to the human population because prevention of the amplification cycle in livestock would greatly reduce the risk of human infection by preventing livestock epizootics. A mutant virus, constructed through the use of reverse genetics, is protective in laboratory animal models and thus shows promise as a potential vaccine. However, the ability to distinguish infected from vaccinated animals is important for vaccine acceptance by national and international authorities, given regulations restricting movement and export of infected animals. Results In this study, we describe the development of a simple assay that can be used to distinguish naturally infected animals from ones that have been vaccinated with a mutant virus. We describe the cloning, expression and purification of two viral proteins, and the development of side by side ELISAs using the two viral proteins. Conclusion A side by side ELISA can be used to differentiate infected from vaccinated animals. This assay can be done without the use of biocontainment facilities and has potential for use in both human and animal populations.

  10. Applying Mathematical Tools to Accelerate Vaccine Development: Modeling Shigella Immune Dynamics

    Science.gov (United States)

    Davis, Courtney L.; Wahid, Rezwanul; Toapanta, Franklin R.; Simon, Jakub K.

    2013-01-01

    We establish a mathematical framework for studying immune interactions with Shigella, a bacteria that kills over one million people worldwide every year. The long-term goal of this novel approach is to inform Shigella vaccine design by elucidating which immune components and bacterial targets are crucial for establishing Shigella immunity. Our delay differential equation model focuses on antibody and B cell responses directed against antigens like lipopolysaccharide in Shigella’s outer membrane. We find that antibody-based vaccines targeting only surface antigens cannot elicit sufficient immunity for protection. Additional boosting prior to infection would require a four-orders-of-magnitude increase in antibodies to sufficiently prevent epithelial invasion. However, boosting anti-LPS B memory can confer protection, which suggests these cells may correlate with immunity. We see that IgA antibodies are slightly more effective per molecule than IgG, but more total IgA is required due to spatial functionality. An extension of the model reveals that targeting both LPS and epithelial entry proteins is a promising avenue to advance vaccine development. This paper underscores the importance of multifaceted immune targeting in creating an effective Shigella vaccine. It introduces mathematical models to the Shigella vaccine development effort and lays a foundation for joint theoretical/experimental/clinical approaches to Shigella vaccine design. PMID:23589755

  11. [The historical development of immunization in Germany. From compulsory smallpox vaccination to a National Action Plan on Immunization].

    Science.gov (United States)

    Klein, S; Schöneberg, I; Krause, G

    2012-11-01

    In the German Reich, smallpox vaccinations were organized by the state. A mandatory vaccination throughout the empire was introduced in 1874, which was continued in the Federal Republic of Germany (FRG) and the German Democratic Republic (GDR) until 1982/1983. From 1935, health departments were responsible for vaccinations. In the GDR, immunization was tightly organized: The state made great efforts to achieve high vaccination rates. Responsibilities were clearly defined at all levels and for all ages. While vaccination was initially mandatory only at the regional level, the legally mandated immunization schedule later contained compulsory vaccinations, e.g., against measles. In the beginning there were mandatory vaccinations in the FRG at the Länder level. Since 1961, the Federal Epidemics Act has impeded obligatory vaccinations. Instead, voluntary vaccinations based on recommendations were stressed. Since the 1980s, vaccinations have been shifted from the public health service sector to office-based physicians. Today, public health authorities offer mainly supplementary vaccinations. In 2007, protective immunizations were introduced as compulsory benefits of the statutory health insurance (SHI). Recently, the German federal states developed a National Vaccination Plan to support immunization strategies.

  12. Advanced Development of the rF1V and rBV A/B Vaccines: Progress and Challenges.

    Science.gov (United States)

    Hart, Mary Kate; Saviolakis, George A; Welkos, Susan L; House, Robert V

    2012-01-01

    The development of vaccines for microorganisms and bacterial toxins with the potential to be used as biowarfare and bioterrorism agents is an important component of the US biodefense program. DVC is developing two vaccines, one against inhalational exposure to botulinum neurotoxins A1 and B1 and a second for Yersinia pestis, with the ultimate goal of licensure by the FDA under the Animal Rule. Progress has been made in all technical areas, including manufacturing, nonclinical, and clinical development and testing of the vaccines, and in assay development. The current status of development of these vaccines, and remaining challenges are described in this chapter.

  13. Advanced Development of the rF1V and rBV A/B Vaccines: Progress and Challenges

    Directory of Open Access Journals (Sweden)

    Mary Kate Hart

    2012-01-01

    Full Text Available The development of vaccines for microorganisms and bacterial toxins with the potential to be used as biowarfare and bioterrorism agents is an important component of the US biodefense program. DVC is developing two vaccines, one against inhalational exposure to botulinum neurotoxins A1 and B1 and a second for Yersinia pestis, with the ultimate goal of licensure by the FDA under the Animal Rule. Progress has been made in all technical areas, including manufacturing, nonclinical, and clinical development and testing of the vaccines, and in assay development. The current status of development of these vaccines, and remaining challenges are described in this chapter.

  14. Utility, limitations and future of non-human primates for dengue research and vaccine development

    Directory of Open Access Journals (Sweden)

    Laura eWhite

    2014-09-01

    Full Text Available Dengue is considered the most important emerging, human arboviruses, with worldwide distribution in the tropics. Unfortunately there are no licensed dengue vaccines available or specific antiviral drugs. The development of a dengue vaccine faces unique challenges. The 4 serotypes co-circulate in endemic areas, and pre-existing immunity to one serotype does not protect against infection with other serotypes, and actually may enhance severity of disease. One foremost constraint to test the efficacy of a dengue vaccine is the lack of an animal model that adequately recapitulates the clinical manifestations of a dengue infection in humans. In spite of this limitation, Non Human Primates (NHP are considered the best available animal model to evaluate dengue vaccine candidates due to their genetic relatedness to humans and their ability to develop a viremia upon infection and a robust immune response similar to that in humans. Therefore, most dengue vaccines candidates are tested in primates before going into clinical trials. In this article we present a comprehensive review of published studies on dengue vaccine evaluations using the NHP model, and discuss critical parameters affecting the usefulness of the model. In the light of recent clinical data, we assess the ability of the NHP model to predict immunological parameters of vaccine performances in humans and discuss parameters that should be further examined as potential correlates of protection. Finally we propose some guidelines towards a more standardized use of the model to maximize its usefulness and to better compare the performance of vaccine candidates from different research groups.

  15. Utility, limitations, and future of non-human primates for dengue research and vaccine development.

    Science.gov (United States)

    Sariol, Carlos A; White, Laura J

    2014-01-01

    Dengue is considered the most important emerging, human arboviruses, with worldwide distribution in the tropics. Unfortunately, there are no licensed dengue vaccines available or specific anti-viral drugs. The development of a dengue vaccine faces unique challenges. The four serotypes co-circulate in endemic areas, and pre-existing immunity to one serotype does not protect against infection with other serotypes, and actually may enhance severity of disease. One foremost constraint to test the efficacy of a dengue vaccine is the lack of an animal model that adequately recapitulates the clinical manifestations of a dengue infection in humans. In spite of this limitation, non-human primates (NHP) are considered the best available animal model to evaluate dengue vaccine candidates due to their genetic relatedness to humans and their ability to develop a viremia upon infection and a robust immune response similar to that in humans. Therefore, most dengue vaccines candidates are tested in primates before going into clinical trials. In this article, we present a comprehensive review of published studies on dengue vaccine evaluations using the NHP model, and discuss critical parameters affecting the usefulness of the model. In the light of recent clinical data, we assess the ability of the NHP model to predict immunological parameters of vaccine performances in humans and discuss parameters that should be further examined as potential correlates of protection. Finally, we propose some guidelines toward a more standardized use of the model to maximize its usefulness and to better compare the performance of vaccine candidates from different research groups.

  16. 76 FR 69743 - The Development and Evaluation of Human Cytomegalovirus Vaccines; Public Workshop

    Science.gov (United States)

    2011-11-09

    ... HUMAN SERVICES Food and Drug Administration The Development and Evaluation of Human Cytomegalovirus... Development and Evaluation of Human Cytomegalovirus Vaccines.'' The purpose of the public workshop is to identify and discuss key issues related to the development and evaluation of human cytomegalovirus (HCMV...

  17. Characterization of S3Pvac anti-cysticercosis vaccine components: implications for the development of an anti-cestodiasis vaccine.

    Directory of Open Access Journals (Sweden)

    Dunia Rassy

    Full Text Available BACKGROUND: Cysticercosis and hydatidosis seriously affect human health and are responsible for considerable economic loss in animal husbandry in non-developed and developed countries. S3Pvac and EG95 are the only field trial-tested vaccine candidates against cysticercosis and hydatidosis, respectively. S3Pvac is composed of three peptides (KETc1, GK1 and KETc12, originally identified in a Taenia crassiceps cDNA library. S3Pvac synthetically and recombinantly expressed is effective against experimentally and naturally acquired cysticercosis. METHODOLOGY/PRINCIPAL FINDINGS: In this study, the homologous sequences of two of the S3Pvac peptides, GK1 and KETc1, were identified and further characterized in Taenia crassiceps WFU, Taenia solium, Taenia saginata, Echinococcus granulosus and Echinococcus multilocularis. Comparisons of the nucleotide and amino acid sequences coding for KETc1 and GK1 revealed significant homologies in these species. The predicted secondary structure of GK1 is almost identical between the species, while some differences were observed in the C terminal region of KETc1 according to 3D modeling. A KETc1 variant with a deletion of three C-terminal amino acids protected to the same extent against experimental murine cysticercosis as the entire peptide. On the contrary, immunization with the truncated GK1 failed to induce protection. Immunolocalization studies revealed the non stage-specificity of the two S3Pvac epitopes and their persistence in the larval tegument of all species and in Taenia adult tapeworms. CONCLUSIONS/SIGNIFICANCE: These results indicate that GK1 and KETc1 may be considered candidates to be included in the formulation of a multivalent and multistage vaccine against these cestodiases because of their enhancing effects on other available vaccine candidates.

  18. Trends in adjuvant development for vaccines: DAMPs and PAMPs as potential new adjuvants

    Directory of Open Access Journals (Sweden)

    E.N. Miyaji

    2011-06-01

    Full Text Available Aluminum salts have been widely used in vaccine formulations and, after their introduction more than 80 years ago, only few vaccine formulations using new adjuvants were developed in the last two decades. Recent advances in the understanding of how innate mechanisms influence the adaptive immunity opened up the possibility for the development of new adjuvants in a more rational design. The purpose of this review is to discuss the recent advances in this field regarding the attempts to determine the molecular basis and the general mechanisms underlying the development of new adjuvants, with particular emphasis on the activation of receptors of innate immune recognition. One can anticipate that the use of these novel adjuvants will also provide a window of opportunities for the development of new vaccines.

  19. Trends in adjuvant development for vaccines: DAMPs and PAMPs as potential new adjuvants.

    Science.gov (United States)

    Miyaji, E N; Carvalho, E; Oliveira, M L S; Raw, I; Ho, P L

    2011-06-01

    Aluminum salts have been widely used in vaccine formulations and, after their introduction more than 80 years ago, only few vaccine formulations using new adjuvants were developed in the last two decades. Recent advances in the understanding of how innate mechanisms influence the adaptive immunity opened up the possibility for the development of new adjuvants in a more rational design. The purpose of this review is to discuss the recent advances in this field regarding the attempts to determine the molecular basis and the general mechanisms underlying the development of new adjuvants, with particular emphasis on the activation of receptors of innate immune recognition. One can anticipate that the use of these novel adjuvants will also provide a window of opportunities for the development of new vaccines.

  20. Development of oral cancer vaccine using recombinant Bifidobacterium displaying Wilms' tumor 1 protein.

    Science.gov (United States)

    Kitagawa, Koichi; Oda, Tsugumi; Saito, Hiroki; Araki, Ayame; Gonoi, Reina; Shigemura, Katsumi; Hashii, Yoshiko; Katayama, Takane; Fujisawa, Masato; Shirakawa, Toshiro

    2017-06-01

    Several types of vaccine-delivering tumor-associated antigens (TAAs) have been developed in basic and clinical research. Wilms' tumor 1 (WT1), identified as a gene responsible for pediatric renal neoplasm, is one of the most promising TAA for cancer immunotherapy. Peptide and dendritic cell-based WT1 cancer vaccines showed some therapeutic efficacy in clinical and pre-clinical studies but as yet no oral WT1 vaccine can be administrated in a simple and easy way. In the present study, we constructed a novel oral cancer vaccine using a recombinant Bifidobacterium longum displaying WT1 protein. B. longum 420 was orally administered into mice inoculated with WT1-expressing tumor cells for 4 weeks to examine anti-tumor effects. To analyze the WT1-specific cellular immune responses to oral B. longum 420, mice splenocytes were isolated and cytokine production and cytotoxic activities were determined. Oral administrations of B. longum 420 significantly inhibited WT1-expressing tumor growth and prolonged survival in mice. Immunohistochemical study and immunological assays revealed that B. longum 420 substantially induced tumor infiltration of CD4 + T and CD8 + T cells, systemic WT1-specific cytokine production, and cytotoxic activity mediated by WT1-epitope specific cytotoxic T lymphocytes, with no apparent adverse effects. Our novel oral cancer vaccine safely induced WT1-specific cellular immunity via activation of the gut mucosal immune system and achieved therapeutic efficacy with several practical advantages over existing non-oral vaccines.

  1. DEVELOPMENT OF VACCINES BASED ON ADENOVIRAL VECTORS: A REVIEW OF FOREIGN CLINICAL STUDIES (PART 2

    Directory of Open Access Journals (Sweden)

    L. V. Cherenova

    2017-01-01

    Full Text Available Currently, many human infectious diseases do not developed effective methods of treatment and prevention. One of the latest successes of biotechnology is the use of adenoviral vectors carrying immunodominant antigens  of various pathogens as genetically engineered vaccines  both  preventive and therapeutic. The use of genetic  engineering technologies allows not  to use in the  manufacture of vaccines  live viruses and  bacteria, reduces  the  time  needed for vaccine  creation and  production of new vaccines.  Adenoviral vectors  naturally penetrate into human cells, causing a rather  long and significant  both humoral and cellular immune response. In the second  part of review, we provide  information about  the ongoing  worldwide  clinical  trials of adenoviral vector-based vaccines against various infectious diseases such as influenza, malaria, Ebola haemorrhagic fever, tuberculosis, hepatitis and  several others, like as to consider selection parameters of volunteers, vaccination schedule, doses of drug administration, results of completed experiments, and preliminary data  on currently ongoing  research.

  2. Vaccination: Developing and implementing a competency-based-curriculum at the Medical Faculty of LMU Munich

    Directory of Open Access Journals (Sweden)

    Vogel, B.

    2016-02-01

    Full Text Available Background: In Germany medical students should gain proficiency and specific skills in the vaccination field. Especially important is the efficient communication of scientific results about vaccinations to the community, in order to give professional counseling with a complete overview about therapeutic options.Aim of the project: The aim of this project is to set up a vaccination-related curriculum in the Medical Faculty at the Ludwig-Maximilians-University in Munich. The structure of the curriculum is based on the National catalogue for competency-based learning objectives in the field of vaccination (Nationaler Kompetenzbasierter Lernzielekatalog Medizin NKLM. Through this curriculum, the students will not only acquire the classical educational skills concerning vaccination in theory and practice, but they will also learn how to become independent in the decision-making process and counseling. Moreover, the students will become aware of consequences of action related to this specific topic.Methods: According to defined guidelines, an analysis was performed on courses, which are currently offered by the university. A separate analysis of the NKLM was carried out. Both analyses identified the active courses related to the topic of vaccination as well as the NKLM learning objectives. The match between the topics taught in current courses and the NKLM learning objectives identified gaps concerning the teaching of specific content. Courses were modified in order to implement the missing NKLM learning objectives.Results: These analyses identified 24 vaccination-related courses, which are currently taught at the University. Meanwhile, 35 learning objectives on vaccination were identified in the NKLM catalogue. Four of which were identified as not yet part of the teaching program. In summary, this interdisciplinary work enabled the development of a new vaccination-related curriculum, including 35 learning objectives, which are now implemented in

  3. Vaccination: Developing and implementing a competency-based-curriculum at the Medical Faculty of LMU Munich.

    Science.gov (United States)

    Vogel, B; Reuter, S; Taverna, M; Fischer, M R; Schelling, J

    2016-01-01

    In Germany medical students should gain proficiency and specific skills in the vaccination field. Especially important is the efficient communication of scientific results about vaccinations to the community, in order to give professional counseling with a complete overview about therapeutic options. AIM OF THE PROJECT: The aim of this project is to set up a vaccination-related curriculum in the Medical Faculty at the Ludwig-Maximilians-University in Munich. The structure of the curriculum is based on the National catalogue for competency-based learning objectives in the field of vaccination (Nationaler Kompetenzbasierter Lernzielekatalog Medizin NKLM). Through this curriculum, the students will not only acquire the classical educational skills concerning vaccination in theory and practice, but they will also learn how to become independent in the decision-making process and counseling. Moreover, the students will become aware of consequences of action related to this specific topic. According to defined guidelines, an analysis was performed on courses, which are currently offered by the university. A separate analysis of the NKLM was carried out. Both analyses identified the active courses related to the topic of vaccination as well as the NKLM learning objectives. The match between the topics taught in current courses and the NKLM learning objectives identified gaps concerning the teaching of specific content. Courses were modified in order to implement the missing NKLM learning objectives. These analyses identified 24 vaccination-related courses, which are currently taught at the University. Meanwhile, 35 learning objectives on vaccination were identified in the NKLM catalogue. Four of which were identified as not yet part of the teaching program. In summary, this interdisciplinary work enabled the development of a new vaccination-related curriculum, including 35 learning objectives, which are now implemented in regular teaching courses by the Medical Faculty

  4. The association between Bacillus Calmette-Guérin vaccination (1331 SSI) skin reaction and subsequent scar development in infants

    DEFF Research Database (Denmark)

    Birk, Nina Marie; Nissen, Thomas Nørrelykke; Ladekarl, Monica

    2017-01-01

    Background: The Bacillus Calmette-Guérin vaccine (BCG) against tuberculosis is administered intradermally, and vaccination is often followed by a scar at the injection site. Among BCG-vaccinated individuals, having a scar has been associated with lower mortality. We aimed to examine the impact...... of vaccination technique for scarring in a high income setting, by assessing the associations between the post injection reaction, the wheal size, and the probability of developing a scar, and scar size. Methods: This study was nested within a clinical multicenter study randomizing 4262 infants to either BCG...... vaccination (BCG 1331 SSI) or no intervention. In this substudy, including 492 vaccinated infants, the immediate post BCG vaccination reaction was registered as either wheal (a raised, blanched papule at the injection site), bulge (a palpable element at the injection site), or no reaction. The presence...

  5. The association between Bacillus Calmette-Guérin vaccination (1331 SSI) skin reaction and subsequent scar development in infants

    DEFF Research Database (Denmark)

    Birk, Nina Marie; Nissen, Thomas Nørrelykke; Ladekarl, Monica

    2017-01-01

    BACKGROUND: The Bacillus Calmette-Guérin vaccine (BCG) against tuberculosis is administered intradermally, and vaccination is often followed by a scar at the injection site. Among BCG-vaccinated individuals, having a scar has been associated with lower mortality. We aimed to examine the impact...... of vaccination technique for scarring in a high income setting, by assessing the associations between the post injection reaction, the wheal size, and the probability of developing a scar, and scar size. METHODS: This study was nested within a clinical multicenter study randomizing 4262 infants to either BCG...... vaccination (BCG 1331 SSI) or no intervention. In this substudy, including 492 vaccinated infants, the immediate post BCG vaccination reaction was registered as either wheal (a raised, blanched papule at the injection site), bulge (a palpable element at the injection site), or no reaction. The presence...

  6. Development of a Preventive HIV Vaccine Requires Solving Inverse Problems Which Is Unattainable by Rational Vaccine Design

    Directory of Open Access Journals (Sweden)

    Marc H. V. Van Regenmortel

    2018-01-01

    Full Text Available Hypotheses and theories are essential constituents of the scientific method. Many vaccinologists are unaware that the problems they try to solve are mostly inverse problems that consist in imagining what could bring about a desired outcome. An inverse problem starts with the result and tries to guess what are the multiple causes that could have produced it. Compared to the usual direct scientific problems that start with the causes and derive or calculate the results using deductive reasoning and known mechanisms, solving an inverse problem uses a less reliable inductive approach and requires the development of a theoretical model that may have different solutions or none at all. Unsuccessful attempts to solve inverse problems in HIV vaccinology by reductionist methods, systems biology and structure-based reverse vaccinology are described. The popular strategy known as rational vaccine design is unable to solve the multiple inverse problems faced by HIV vaccine developers. The term “rational” is derived from “rational drug design” which uses the 3D structure of a biological target for designing molecules that will selectively bind to it and inhibit its biological activity. In vaccine design, however, the word “rational” simply means that the investigator is concentrating on parts of the system for which molecular information is available. The economist and Nobel laureate Herbert Simon introduced the concept of “bounded rationality” to explain why the complexity of the world economic system makes it impossible, for instance, to predict an event like the financial crash of 2007–2008. Humans always operate under unavoidable constraints such as insufficient information, a limited capacity to process huge amounts of data and a limited amount of time available to reach a decision. Such limitations always prevent us from achieving the complete understanding and optimization of a complex system that would be needed to achieve a truly

  7. Development of a whole cell pneumococcal vaccine: BPL inactivation, cGMP production, and stability.

    Science.gov (United States)

    Gonçalves, Viviane M; Dias, Waldely O; Campos, Ivana B; Liberman, Celia; Sbrogio-Almeida, Maria E; Silva, Eliane P; Cardoso, Celso P; Alderson, Mark; Robertson, George; Maisonneuve, Jean-François; Tate, Andrea; Anderson, Porter; Malley, Richard; Fratelli, Fernando; Leite, Luciana C C

    2014-02-19

    Pneumococcal infections impose a large burden of disease on the human population, mainly in developing countries, and the current pneumococcal vaccines offer serotype-specific protection, but do not cover all pathogenic strains, leaving populations vulnerable to disease caused by non-vaccine serotypes. The pneumococcal whole cell vaccine is a low-cost strategy based on non-capsular antigens common to all strains, inducing serotype-independent immunity. Therefore, we developed the process for the cGMP production of this cellular vaccine. Initially, three engineering runs and two cGMP runs were performed in 60-L bioreactors, demonstrating the consistency of the production process, as evaluated by the growth curves, glucose consumption and metabolite formation (lactate and acetate). Cell recovery by tangential filtration was 92 ± 13 %. We optimized the conditions for beta-propiolactone (BPL) inactivation of the bacterial suspensions, establishing a maximum cell density of OD600 between 27 and 30, with a BPL concentration of 1:4000 (v/v) at 150 rpm and 4 °C for 30 h. BPL was hydrolyzed by heating for 2h at 37 °C. The criteria and methods for quality control were defined using the engineering runs and the cGMP Lots passed all specifications. cGMP vaccine Lots displayed high potency, inducing between 80 and 90% survival in immunized mice when challenged with virulent pneumococci. Sera from mice immunized with the cGMP Lots recognized several pneumococcal proteins in the extract of encapsulated strains by Western blot. The cGMP whole cell antigen bulk and whole cell vaccine product lots were shown to be stable for up to 12 and 18 months, respectively, based upon survival assays following i.p. challenge. Our results show the consistency and stability of the cGMP whole cell pneumococcal vaccine lots and demonstrate the feasibility of production in a developing country setting. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. Protective value of immune responses developed in goats vaccinated with insoluble proteins from Sarcoptes Scabiei

    Directory of Open Access Journals (Sweden)

    Simson Tarigan

    2005-06-01

    Full Text Available Vaccines developed from certain membrane proteins lining the lumen of arthropod’s gut have been demonstrated effective in the control of some arthropod ectoparasites. A similar approach could also be applied to Sarcoptes scabiei since this parasite also ingests its host immunoglobulins. To evaluate immune protection of the membrane proteins, insoluble mite proteins were fractionated by successive treatment in the solutions of 1.14 M NaCl, 2% SB 3-14 Zwitterion detergent, 6 M urea, 6 M guanidine-HCl and 5% SDS. Five groups of goats (6 or 7 goats per group were immunised respectively with the protein fractions. Vaccination was performed 6 times, each with a dosage of 250 μg proteins, and 3 week intervals between vaccination. Group 6 (7 goats received PBS and adjuvant only, and served as an unvaccinated control. One week after the last vaccination, all goats were challenged with 2000 live mites on the auricles. The development of lesions were examined at 1 day, 2 days, and then every week from week 1 to 8. All animals were bled and weighed every week, and at the end of the experiment, skin scrapings were collected to determine the mite burden. Antibody responses induced by vaccination and challenge were examined by ELISA and Western blotting. This experiment showed that vaccination with the insoluble-protein fractions resulted in the development of high level of specific antibodies but the responses did not have any protective value. The severity of lesions and mite burden in the vaccinated animals were not different from those in the unvaccinated control.

  9. Rotavirus vaccines.

    Science.gov (United States)

    Lynch, Maureen; Bresee, Joseph S.; Gentsch, Jon R.; Glass, Roger I.

    2000-10-01

    The past few years have seen important developments in understanding the epidemiological and virological characteristics of rotaviruses, and rapid progress has been made in rotavirus vaccine development, but further challenges remain before a vaccine is introduced into widespread use. The licensure of the first rotavirus vaccine, a tetravalent rhesus-based rotavirus vaccine, in the United States in 1998, marked a significant advance in preventing the morbidity associated with rotavirus diarrhea. The association between the tetravalent rhesus-based rotavirus vaccine and intussusception has created significant hurdles as well as new opportunities to study the pathogenesis of rotavirus and rotavirus vaccine infection. Several other rotavirus vaccine candidates are in late stages of development, and results from trials have been encouraging.

  10. Use of recombinant capsid proteins in the development of a vaccine against foot-and-mouth disease virus (FMDV)

    DEFF Research Database (Denmark)

    Belsham, Graham; Bøtner, Anette

    2015-01-01

    -scale culling of infected, and potentially infected, animals there has been significant effort to develop new vaccines against this disease which avoid some, or all, of the deficiencies of current vaccines. A major focus has been on the use of systems that express the structural proteins of the virus that self....... The development and use of such improved vaccines should assist in the global efforts to control this important disease...

  11. Development and evaluation of a novel vaccine against prevalent invasive multi-drug resistant strains of Streptococcus pneumoniae

    Directory of Open Access Journals (Sweden)

    Rehab H. Bahy

    2016-11-01

    Full Text Available Streptococcus pneumoniae is a pathogen that causes serious invasive infections, such as septicemia, meningitis and pneumonia in addition to mild upper respiratory tract infections. Protection from pneumococcal diseases is thought to be mediated mainly by serotype-specific antibodies to capsular antigens. Pneumococcal conjugate vaccine consists of sugars (polysaccharides from the capsule of the bacterium S. pneumoniae that are conjugated to a carrier protein. Three pneumococcal conjugated vaccines, each directed against a group of serotypes, are registered in Egypt; however, local vaccine production is required to cover the most prevalent serotypes. In this work, capsular polysaccharide from the most current and prevalent serotypes in Egypt were extracted, purified and conjugated to bovine serum albumin (BSA. The polysaccharide protein conjugate was purified through ultrafiltration technique and molecular size distribution was compared to an available vaccine. The immunogenicity of the prepared vaccine was examined via two methods: First, by measuring the levels of the elicited antibodies in the sera of the vaccinated mice; second, by challenging the vaccinated groups of mice with approximately 107 CFU of each specific serotype and determining the degree of protection the developled vaccine offers. Our results show that the developed conjugated capsular polysaccharide vaccine is highly immunogenic and protective in mice. This finding illustrates the importance of tracking the most recent and predominant peneumococcal serotypes to generate effective vaccines, instead of using expensive imported vaccines with large number of serotypes which might not be even present in the community.

  12. Cytolethal distending toxin as virulence factor, protective antigen, and target for vaccine development

    Directory of Open Access Journals (Sweden)

    Lagergård T

    2012-12-01

    Full Text Available Teresa Lagergård,1 Jerry Keith21Institute of Biomedicine, Department of Microbiology and Immunology, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden; 2Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD, NIH, Bethesda, MD, USAAbstract: This review explores the cytolethal distending toxin (CDT as a virulence factor, protective antigen, and a vaccine candidate in diseases caused by the following bacterial pathogens: Haemophilus ducreyi (HdCDT, Aggregatibacter actinomycetemcomitans, Campylobacter jejuni, and Helicobacter hepaticus. The review highlights some of the important evidence indicating that CDT is not only a commonly invoked virulence factor involved in pathogenesis of infection caused by these bacteria, but is also a protective antigen, such that specific antibodies will neutralize cell damage caused by the toxin. This justifies the development of toxoids as vaccine candidates. The first immunogenic toxoid was produced by formaldehyde treatment of HdCDT and has been used to study the involvement of antibodies in protection against infection and its use as a future vaccine component. The development of such toxoid vaccines may facilitate the studies of protection and immunoprophylaxis in diseases caused by CDT-producing bacteria.Keywords: cytolethal distending toxin, virulence factor, protective antigen, Haemophilus ducreyi, Aggregatibacter actinomycetemcomitans, Campylobacter jejuni, toxoid vaccine

  13. The need and challenges for development of an Epstein-Barr virus vaccine.

    Science.gov (United States)

    Cohen, Jeffrey I; Mocarski, Edward S; Raab-Traub, Nancy; Corey, Lawrence; Nabel, Gary J

    2013-04-18

    Epstein-Barr virus (EBV) is the major cause of infectious mononucleosis and is associated with several malignancies including nasopharyngeal carcinoma, gastric carcinoma, Hodgkin lymphoma, Burkitt lymphoma, and lymphoma after organ or stem cell transplant. A candidate vaccine containing soluble EBV glycoprotein gp350 protected cottontop tamarins from EBV lymphoma after challenge with EBV. In the only phase 2 trial of an EBV vaccine in humans, soluble gp350 in alum and monophosphoryl lipid A adjuvant reduced the rate of infectious mononucleosis in EBV seronegative adults, but did not affect the rate of EBV infection. A peptide vaccine corresponding to EBV latency proteins has been tested in a small number of adults to prevent infectious mononucleosis. Some of the barriers to development of an EBV vaccine include (a) whether viral proteins in addition to gp350 would be more effective for preventing mononucleosis or EBV malignancies, (b) the difficulty of performing clinical trials to prevent EBV associated malignancies in the absence of good surrogate markers for tumor development, and the long period of time between primary EBV infection and development of many EBV tumors, (c) the lack of knowledge of immune correlates for protection against EBV infection and disease, (d) the limitations in animal models to study protection against EBV infection and disease, and (e) the need for additional information on the economic and societal burden of infectious mononucleosis to assess the cost-benefit of a prophylactic vaccine. Copyright © 2013. Published by Elsevier Ltd.

  14. Mucosal immunity and HIV-1 infection: applications for mucosal AIDS vaccine development.

    Science.gov (United States)

    Belyakov, Igor M; Ahlers, Jeffrey D

    2012-01-01

    Natural transmission of human immunodeficiency virus type 1 (HIV-1) occurs through gastrointestinal and vaginal mucosa. These mucosal tissues are major reservoirs for initial HIV replication and amplification, and the sites of rapid CD4(+) T cell depletion. In both HIV-infected humans and SIV-infected macaques, massive loss of CD4(+) CCR5(+) memory T cells occurs in the gut and vaginal mucosa within the first 10-14 days of infection. Induction of local HIV-specific immune responses by vaccines may facilitate effective control of HIV or SIV replication at these sites. Vaccines that induce mucosal responses, in particular CD8(+) cytotoxic T lymphocytes (CTL), have controlled viral replication at mucosal sites and curtailed systemic dissemination. Thus, there is strong justification for development of next generation vaccines that induce mucosal immune effectors against HIV-1 including CD8(+) CTL, CD4(+) T helper cells and secretory IgA. In addition, further understanding of local innate mechanisms that impact early viral replication will greatly inform future vaccine development. In this review, we examine the current knowledge concerning mucosal AIDS vaccine development. Moreover, we propose immunization strategies that may be able to elicit an effective immune response that can protect against AIDS as well as other mucosal infections.

  15. Planning and priority setting for vaccine development and immunization.

    Science.gov (United States)

    Phelps, Charles E; Madhavan, Guruprasad; Gellin, Bruce

    2017-01-20

    We review a sequence of strategic planning efforts over time in the United States, all involving processes to prioritize new vaccine candidates. The Institute of Medicine of the National Academies of Sciences, Engineering, and Medicine has been involved in three priority setting processes, each using different metrics and methodologies: infant mortality equivalents (1985-1986), cost-effectiveness (2000), and more recently, the implementation of a software system based on a broader multi-criteria systems approach that can include either of the earlier metrics among other various considerations (2015). The systems approach offers users the flexibility to select, combine, rank, weigh and evaluate different attributes representing their perspectives, assumptions, and particular needs. This approach also overcomes concerns relating to the previous single-metric ranking approaches that yielded lists that, once published, were static, and could not readily accommodate new information about emerging pathogens, new scientific advances, or changes in the costs and performance features of interventions. We discuss the rationale and reasoning behind the design of this multi-criteria decision support approach, stakeholder feedback about the tool, and highlight the potential advantages from using this expanded approach to better inform and support vaccine policies. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Clinical development of a recombinant Ebola vaccine in the midst of an unprecedented epidemic.

    Science.gov (United States)

    Coller, Beth-Ann G; Blue, Jeffrey; Das, Rituparna; Dubey, Sheri; Finelli, Lynn; Gupta, Swati; Helmond, Frans; Grant-Klein, Rebecca J; Liu, Kenneth; Simon, Jakub; Troth, Sean; VanRheenen, Susan; Waterbury, Julie; Wivel, Ashley; Wolf, Jayanthi; Heppner, D Gray; Kemp, Tracy; Nichols, Rick; Monath, Thomas P

    2017-08-16

    The 2014-2016 Ebola outbreak caused over 28,000 cases and 11,000 deaths. Merck & Co. Inc., Kenilworth, NJ USA and NewLink Genetics are working with private and public partners to develop and license an Ebola vaccine that was evaluated extensively during the outbreak. The vaccine referred to as V920 is a recombinant vesicular stomatitis virus (rVSV) in which the VSV-G envelope glycoprotein (GP) is completely replaced by the Zaire ebolavirus GP (rVSVΔG-ZEBOV-GP). Eight Phase I and four Phase II/III clinical trials enrolling approximately 17,000 subjects were conducted in parallel to the outbreak to assess the safety, immunogenicity, and/or efficacy of V920. Immunogenicity data demonstrate that anti-GP antibodies are generally detectable by ELISA by 14days postvaccination with up to 100% seroconversion observed by 28days post dose. In addition, the results of a ring vaccination trial conducted by the WHO and their partners in Guinea suggest robust vaccine efficacy within 10days of receipt of a single dose of vaccine. The vaccine is generally well-tolerated when administered to healthy, non-pregnant adults. The development of this vaccine candidate in the context of this unprecedented epidemic has involved the close cooperation of large number of international partners and highlights what we as a public health community can accomplish when working together towards a common goal. Study identification: V920-001 to V920-012. CLINICALTRIALS.GOV identifiers: NCT02269423; NCT02280408; NCT02374385; NCT02314923; NCT02287480; NCT02283099; NCT02296983; NCT02344407; NCT02378753; NCT02503202. Copyright © 2017. Published by Elsevier Ltd.

  17. Avian influenza vaccine development: Application technology platforms, field use and predictors of protection

    Science.gov (United States)

    Vaccines against avian influenza (AI) began over 100 years ago as experimentally produced products, but commercial application did not occur until: 1) a reliable method was developed to grow and titer the virus (i.e. embryonating chicken eggs), 2) an efficient and predictable method was developed to...

  18. A pilot study on developing mucosal vaccine against alveolar echinococcosis (AE using recombinant tetraspanin 3: Vaccine efficacy and immunology.

    Directory of Open Access Journals (Sweden)

    Zhisheng Dang

    Full Text Available BACKGROUND: We have previously evaluated the vaccine efficacies of seven tetraspanins of Echinococcus multilocularis (Em-TSP1-7 against alveolar echinococcosis (AE by subcutaneous (s.c. administration with Freund's adjuvant. Over 85% of liver cyst lesion number reductions (CLNR were achieved by recombinant Em-TSP1 (rEm-TSP1 and -TSP3 (rEm-TSP3. However, to develop an efficient and safe human vaccine, the efficacy of TSP mucosal vaccines must be thoroughly evaluated. METHODOLOGY/PRINCIPAL FINDINGS: rEm-TSP1 and -TSP3 along with nontoxic CpG ODN (CpG oligodeoxynucleotides adjuvant were intranasally (i.n. immunized to BALB/c mice and their vaccine efficacies were evaluated by counting liver CLNR (experiment I. 37.1% (p < 0.05 and 62.1% (p < 0.001 of CLNR were achieved by these two proteins, respectively. To study the protection-associated immune responses induced by rEm-TSP3 via different immunization routes (i.n. administration with CpG or s.c. immunization with Freund's adjuvant, the systemic and mucosal antibody responses were detected by ELISA (experiment II. S.c. and i.n. administration of rEm-TSP3 achieved 81.9% (p < 0.001 and 62.8% (p < 0.01 CLNR in the liver, respectively. Both the immunization routes evoked strong serum IgG, IgG1 and IgG2α responses; i.n. immunization induced significantly higher IgA responses in nasal cavity and intestine compared with s.c. immunization (p < 0.001. Both immunization routes induced extremely strong liver IgA antibody responses (p < 0.001. The Th1 and Th2 cell responses were assessed by examining the IgG1/IgG2α ratio at two and three weeks post-immunization. S.c. immunization resulted in a reduction in the IgG1/IgG2α ratio (Th1 tendency, whereas i.n. immunization caused a shift from Th1 to Th2. Moreover, immunohistochemistry showed that Em-TSP1 and -TSP3 were extensively located on the surface of E. multilocularis cysts, protoscoleces and adult worms with additional expression of Em-TSP3 in the inner

  19. Comparison of functional assays used in the clinical development of a placental malaria vaccine

    DEFF Research Database (Denmark)

    Pehrson, Caroline; Heno, Kristine Klysner; Adams, Yvonne

    2017-01-01

    BACKGROUND: Malaria in pregnancy is associated with significant morbidity in pregnant women and their offspring. Plasmodium falciparum infected erythrocytes (IE) express VAR2CSA that mediates binding to chondroitin sulphate A (CSA) in the placenta. Two VAR2CSA-based vaccines for placental malaria...... are in clinical development. The purpose of this study was to evaluate the robustness and comparability of binding inhibition assays used in the clinical development of placental malaria vaccines. METHODS: The ability of sera from animals immunised with different VAR2CSA constructs to inhibit IE binding to CSA...

  20. The pig as a large preclinical model for therapeutic human anti-cancer vaccine development

    DEFF Research Database (Denmark)

    Overgaard, Nana Haahr; Frøsig, Thomas Mørch; Welner, Simon

    2016-01-01

    Development of therapeutic cancer vaccines has largely been based on rodent models and the majority failed to establish therapeutic responses in clinical trials. We therefore used pigs as a large animal model for human cancer vaccine development due to the large similarity between the porcine...... response. To test the CTL functionality we designed an in vivo cytotoxicity assay, where purified autologous PBMCs fluorescently labelled and pulsed with IDO-derived target peptides were administered intravenously into each donor and killing capacity was measured by flow cytometry. All animals receiving 10...

  1. GeVaDSs – decision support system for novel Genetic Vaccine development process

    Directory of Open Access Journals (Sweden)

    Blazewicz Jacek

    2012-05-01

    Full Text Available Abstract Background The lack of a uniform way for qualitative and quantitative evaluation of vaccine candidates under development led us to set up a standardized scheme for vaccine efficacy and safety evaluation. We developed and implemented molecular and immunology methods, and designed support tools for immunization data storage and analyses. Such collection can create a unique opportunity for immunologists to analyse data delivered from their laboratories. Results We designed and implemented GeVaDSs (Genetic Vaccine Decision Support system an interactive system for efficient storage, integration, retrieval and representation of data. Moreover, GeVaDSs allows for relevant association and interpretation of data, and thus for knowledge-based generation of testable hypotheses of vaccine responses. Conclusions GeVaDSs has been tested by several laboratories in Europe, and proved its usefulness in vaccine analysis. Case study of its application is presented in the additional files. The system is available at: http://gevads.cs.put.poznan.pl/preview/(login: viewer, password: password.

  2. Development of novel double-decker microneedle patches for transcutaneous vaccine delivery.

    Science.gov (United States)

    Ono, Akihiko; Azukizawa, Hiroaki; Ito, Sayami; Nakamura, Yuki; Asada, Hideo; Quan, Ying-Shu; Kamiyama, Fumio; Katayama, Ichiro; Hirobe, Sachiko; Okada, Naoki

    2017-10-30

    Microneedle (MN) patches have great potential as transcutaneous vaccine delivery devices because MNs can effectively deliver vaccine antigen into the skin through the micropores formed in the stratum corneum by low-invasive and painless skin puncturing. This study aims to develop novel double-decker MN patches which have not only high safety and efficacy but also broad applicability to various vaccine antigens. We developed two types of MN patches (PGA-MN and Nylon-MN) that are made from polyglycolic acid and Nylon-6. In pre-clinical studies, both MN patches could demonstrably deliver antigens into resected human dermal tissue, prolong antigen deposition and increase antigen-specific IgG levels after vaccination compared with conventional injections. We demonstrated both MN patches could be safely applied to human skin because no broken MNs or significant skin irritation were observed after applications in the clinical research. PGA-MN was suggested to be superior to Nylon-MN regarding human skin puncturability based on measurements of transepidermal water loss and needle failure force. A high content of tetravalent influenza hemagglutinin antigens loaded on PGA-MN could stably maintain HA titers at 35°C for 1year. Overall, double-decker MN patches can reliably and safely puncture human skin and are promising as effective transcutaneous vaccine delivery devices. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Progress toward the Development of a NEAT Protein Vaccine for Anthrax Disease.

    Science.gov (United States)

    Balderas, Miriam A; Nguyen, Chinh T Q; Terwilliger, Austen; Keitel, Wendy A; Iniguez, Angelina; Torres, Rodrigo; Palacios, Frederico; Goulding, Celia W; Maresso, Anthony W

    2016-12-01

    Bacillus anthracis is a sporulating Gram-positive bacterium that is the causative agent of anthrax and a potential weapon of bioterrorism. The U.S.-licensed anthrax vaccine is made from an incompletely characterized culture supernatant of a nonencapsulated, toxigenic strain (anthrax vaccine absorbed [AVA]) whose primary protective component is thought to be protective antigen (PA). AVA is effective in protecting animals and elicits toxin-neutralizing antibodies in humans, but enthusiasm is dampened by its undefined composition, multishot regimen, recommended boosters, and potential for adverse reactions. Improving next-generation anthrax vaccines is important to safeguard citizens and the military. Here, we report that vaccination with recombinant forms of a conserved domain (near-iron transporter [NEAT]), common in Gram-positive pathogens, elicits protection in a murine model of B. anthracis infection. Protection was observed with both Freund's and alum adjuvants, given subcutaneously and intramuscularly, respectively, with a mixed composite of NEATs. Protection correlated with an antibody response against the NEAT domains and a decrease in the numbers of bacteria in major organs. Anti-NEAT antibodies promote opsonophagocytosis of bacilli by alveolar macrophages. To guide the development of inactive and safe NEAT antigens, we also report the crystal structure of one of the NEAT domains (Hal) and identify critical residues mediating its heme-binding and acquisition activity. These results indicate that we should consider NEAT proteins in the development of an improved antianthrax vaccine. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  4. Lack of a Negative Effect of BCG-Vaccination on Child Psychomotor Development

    DEFF Research Database (Denmark)

    Kjærgaard, Jesper; Stensballe, Lone Graff; Birk, Nina Marie

    2016-01-01

    OBJECTIVES: To assess the non-specific effect of Bacillus Calmette-Guérin (BCG) vaccination at birth on psychomotor development. DESIGN: This is a pre-specified secondary outcome from a randomised, clinical trial. SETTING: Maternity units and paediatric wards at three university hospitals...... and 2133 randomised (73 premature) to the control group. INTERVENTIONS: BCG vaccination 0.05 ml was given intradermally in the upper left arm at the hospital within seven days of birth. Children in the control group did not receive any intervention. Parents were not blinded to allocation. MAIN OUTCOME...... was -7.8 points (-20.6 to 5.0, p = 0.23), d = -0.23 (-0.62 to 0.15). CONCLUSIONS: A negative non-specific effect of BCG vaccination at birth on psychomotor development was excluded in term children. TRIAL REGISTRATION: ClinicalTrials.gov NCT01694108....

  5. Toward the development of effective transmission-blocking vaccines for malaria.

    Science.gov (United States)

    Nikolaeva, Daria; Draper, Simon J; Biswas, Sumi

    2015-05-01

    The continued global burden of malaria can in part be attributed to a complex lifecycle, with both human hosts and mosquito vectors serving as transmission reservoirs. In preclinical models of vaccine-induced immunity, antibodies to parasite sexual-stage antigens, ingested in the mosquito blood meal, can inhibit parasite survival in the insect midgut as judged by ex vivo functional studies such as the membrane feeding assay. In an era of renewed political momentum for malaria elimination and eradication campaigns, such observations have fueled support for the development and implementation of so-called transmission-blocking vaccines. While leading candidates are being evaluated using a variety of promising vaccine platforms, the field is also beginning to capitalize on global '-omics' data for the rational genome-based selection and unbiased characterization of parasite and mosquito proteins to expand the candidate list. This review covers the progress and prospects of these recent developments.

  6. Development and evaluation of two subunit vaccine candidates containing antigens of hepatitis E virus, rotavirus, and astrovirus.

    Science.gov (United States)

    Xia, Ming; Wei, Chao; Wang, Leyi; Cao, Dianjun; Meng, Xiang-Jin; Jiang, Xi; Tan, Ming

    2016-05-19

    Hepatitis E virus (HEV), rotavirus (RV), and astrovirus (AstV) are important pathogens that transmit through a common fecal-oral route, causing hepatitis (HEV) and gastroenteritis (RV and AstV) respectively in humans. In this study, we developed and evaluated two subunit vaccine candidates that consisted of the same protruding or spike protein antigens of the three viruses in two formats, a fusion of the three antigens into one molecule (fused vaccine) vs. a mixture of the three free antigens together (mixed vaccine). Both vaccines were easily made via E. coli expression system. Mouse immunization experiments showed that the fused vaccine elicited significantly higher antibody responses against the three viral antigens than those induced by the mixed vaccine. In addition, the mouse post-immune antisera of the fused vaccine revealed significantly higher neutralizing titers against HEV infection in cell culture, as well as significantly higher 50% blocking titers (BT50) against RV VP8-HBGA receptor interactions than those of the post-immune antisera after immunization of the mixed vaccine. Thus, the fused vaccine is a promising trivalent vaccine candidate against HEV, RV, and AstV, which is worth for further development.

  7. Contraceptive Vaccines

    Directory of Open Access Journals (Sweden)

    M.V. Supotnitsky

    2014-02-01

    Full Text Available Researches to develop vaccines with contraceptive effect are being carried out since the 1920s. Since 1972, the contraceptive vaccines are one of the priority programs of the World Health Organization (WHO Special Programme of Research, Development and Research Training in Human Reproduction. Rockefeller Foundation participates in implementing the program. Openly declared objective of creating such vaccines — the regulation of the population in the Third World countries. There are currently three main directions of contraceptive vaccine design: 1 vaccines targeted at blocking the production of gametes; 2 impairing their function; 3 violating the fertilization process. Contraceptive vaccines for more than 10 years are widely used to reduce fertility and castration of wild and domestic animals. In the commercial realization there are veterinary vaccines Equity®, Improvac®, GonaCon®, Repro-BLOC (based on gonadotropin-releasing hormone; SpayVac™ and IVT-PZP® (based on zona pellucida antigens. Clinical studies have shown effective contraceptive action (in women of vaccines, in which human chorionic gonadotropin is used as an antigen. At the same time, there are found the side effects of such vaccines: for vaccines containing gonadotropin-releasing hormone and luteinizing hormone as antigenic components — castration, impotence; for vaccines containing follicle stimulating hormone — oligospermia; zona pellucida antigens — irreversible oophoritis. This paper discusses approaches to detection of sterilizing components in vaccines intended for mass prevention of infectious diseases, not reported by manufacturers, and the consequences of their use. Hidden use of contraceptive vaccines, which already took place, can be detected: 1 by the presence of antibodies to their antigenic components (in unvaccinated by contraceptive vaccines people such antibodies do not exist, except infertility cases; 2 by change in the hormonal levels of the

  8. Application of a Scalable Plant Transient Gene Expression Platform for Malaria Vaccine Development.

    Science.gov (United States)

    Spiegel, Holger; Boes, Alexander; Voepel, Nadja; Beiss, Veronique; Edgue, Gueven; Rademacher, Thomas; Sack, Markus; Schillberg, Stefan; Reimann, Andreas; Fischer, Rainer

    2015-01-01

    Despite decades of intensive research efforts there is currently no vaccine that provides sustained sterile immunity against malaria. In this context, a large number of targets from the different stages of the Plasmodium falciparum life cycle have been evaluated as vaccine candidates. None of these candidates has fulfilled expectations, and as long as we lack a single target that induces strain-transcending protective immune responses, combining key antigens from different life cycle stages seems to be the most promising route toward the development of efficacious malaria vaccines. After the identification of potential targets using approaches such as omics-based technology and reverse immunology, the rapid expression, purification, and characterization of these proteins, as well as the generation and analysis of fusion constructs combining different promising antigens or antigen domains before committing to expensive and time consuming clinical development, represents one of the bottlenecks in the vaccine development pipeline. The production of recombinant proteins by transient gene expression in plants is a robust and versatile alternative to cell-based microbial and eukaryotic production platforms. The transfection of plant tissues and/or whole plants using Agrobacterium tumefaciens offers a low technical entry barrier, low costs, and a high degree of flexibility embedded within a rapid and scalable workflow. Recombinant proteins can easily be targeted to different subcellular compartments according to their physicochemical requirements, including post-translational modifications, to ensure optimal yields of high quality product, and to support simple and economical downstream processing. Here, we demonstrate the use of a plant transient expression platform based on transfection with A. tumefaciens as essential component of a malaria vaccine development workflow involving screens for expression, solubility, and stability using fluorescent fusion proteins. Our

  9. Application of a scalable plant transient gene expression platform for malaria vaccine development

    Directory of Open Access Journals (Sweden)

    Holger eSpiegel

    2015-12-01

    Full Text Available Despite decades of intensive research efforts there is currently no vaccine that provides sustained sterile immunity against malaria. In this context, a large number of targets from the different stages of the Plasmodium falciparum life cycle have been evaluated as vaccine candidates. None of these candidates has fulfilled expectations, and as long as we lack a single target that induces strain-transcending protective immune responses, combining key antigens from different life cycle stages seems to be the most promising route towards the development of efficacious malaria vaccines. After the identification of potential targets using approaches such as omics-based technology and reverse immunology, the rapid expression, purification and characterization of these proteins, as well as the generation and analysis of fusion constructs combining different promising antigens or antigen domains before committing to expensive and time consuming clinical development, represents one of the bottlenecks in the vaccine development pipeline. The production of recombinant proteins by transient gene expression in plants is a robust and versatile alternative to cell-based microbial and eukaryotic production platforms. The transfection of plant tissues and/or whole plants using Agrobacterium tumefaciens offers a low technical entry barrier, low costs and a high degree of flexibility embedded within a rapid and scalable workflow. Recombinant proteins can easily be targeted to different subcellular compartments according to their physicochemical requirements, including post-translational modifications, to ensure optimal yields of high quality product, and to support simple and economical downstream processing. Here we demonstrate the use of a plant transient expression platform based on transfection with A. tumefaciens as essential component of a malaria vaccine development workflow involving screens for expression, solubility and stability using fluorescent fusion

  10. Strategies for Developing Oral Vaccines for Human Papillomavirus (HPV) Induced Cancer using Nanoparticle mediated Delivery System.

    Science.gov (United States)

    Uddin, Mohammad Nasir; Kouzi, Samir A; Hussain, Muhammad Delwar

    2015-01-01

    Human Papillomaviruses (HPV) are a diverse group of small non-enveloped DNA viruses. Some HPVs are classified as low-risk as they are very rarely associated with neoplasia or cancer in the general population, and cause lenient warts. Other HPVs are considered as high-risk types because they are responsible for several important human cancers, including cervical cancer, a large proportion of other anogenital cancers, and a growing number of head and neck cancers. Transmission of HPV occurs primarily by skin-to-skin contact. The risk of contracting genital HPV infection and cervical cancer is influenced by sexual activity. Currently two prophylactic HPV vaccines, Gardasil® (Merck, USA) and Cervarix® (GlaxoSmithKline, UK), are available and recommended for mass immunization of adolescents. However, these vaccines have limitations as they are expensive and require cold chain storage and trained personnel to administer them by injection. The use of nano or micro particulate vaccines could address most of these limitations as they are stable at room temperature, inexpensive to produce and distribute to resource poor regions, and can be administered orally without the need for adjuvants in the formulation. Also it is possible to increase the efficiency of these particulate vaccines by decorating the surface of the nano or micro particulates with suitable ligands for targeted delivery. Oral vaccines, which can be delivered using particulate formulations, have the added potential to stimulate mucosa-associated lymphoid tissue located in the digestive tract and the gut-associated lymphoid tissue, both of which are important for the induction of effective mucosal response against many viruses. In addition, oral vaccines provide the opportunity to reduce production and administration costs and are very patient compliant. This review elaborately discusses different strategies that can be pursued to develop a nano or micro particulate oral vaccine for HPV induced cancers and

  11. A real options approach to biotechnology investment policy-the case of developing a Campylobacter vaccine to poultry.

    Science.gov (United States)

    Lund, Mogens; Jensen, Jørgen Dejgård

    2016-06-01

    The aim of the article is to identify and analyse public-private incentives for the development and marketing of new animal vaccines within a real options methodological framework, and to investigate how real options methodology can be utilized to support economic incentives for vaccine development in a cost-effective way. The development of a vaccine against Campylobacter jejuni in poultry is applied as a case study. Employing the real options methodology, the net present value of the vaccine R&D project becomes larger than a purely probabilistic expected present value throughout the different stages of the project - and the net present value becomes larger, when more types of real options are taken into consideration. The insight from the real options analysis reveals opportunities for new policies to promote the development of animal vaccines. One such approach might be to develop schemes combining stage-by-stage optimized subsidies in the individual development stages, with proper account taken of investors'/developers' economic incentives to proceed, sell or cancel the project in the respective stages. Another way of using the real options approach to support the development of desirable animal vaccines could be to issue put options for the vaccine candidate, enabling vaccine developers to hedge against the economic risk from market volatility. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Development and clinical evaluation of multiple investigational monovalent DENV vaccines to identify components for inclusion in a live attenuated tetravalent DENV vaccine

    Science.gov (United States)

    Durbin, Anna P.; Kirkpatrick, Beth D.; Pierce, Kristen K.; Schmidt, Alexander C.; Whitehead, Stephen S.

    2011-01-01

    The Laboratory of Infectious Diseases at the National Institute of Allergy and Infectious Diseases, National Institutes of Health has been engaged in an effort to develop a safe, efficacious, and affordable live attenuated tetravalent dengue vaccine (LATV) for more than ten years. Numerous recombinant monovalent DENV vaccine candidates have been evaluated in the SCID-HuH-7 mouse and in rhesus macaques to identify those candidates with a suitable attenuation phenotype. In addition, the ability of these candidates to infect and disseminate in Aedes mosquitoes had also been determined. Those candidates that were suitably attenuated in SCID-HuH-7 mice, rhesus macaques, and mosquitoes were selected for further evaluation in humans. This review will describe the generation of multiple candidate vaccines directed against each DENV serotype, the preclinical and clinical evaluation of these candidates, and the process of selecting suitable candidates for inclusion in a LATV dengue vaccine. PMID:21781997

  13. Developing an Inactivated Rotavirus Vaccine and Evaluating the Immunogenicity Against a Commercially Available Attenuated Rotavirus Vaccine Using a Mice Animal Model.

    Science.gov (United States)

    Hashim, Ayaa S M; Aboshanab, Khaled M A; El-Sayed, Aly F M

    2016-12-01

    There is a high demand for public immunization against Rotavirus (RV), especially in Africa. In Africa, the attenuated RV vaccination is contraindicated in patients with immune diseases and nutrition deficiency. Therefore, the inactivated RV vaccine (IRVV) could be an alternative. In this study, we aimed to develop a pentavalent-IRVV using the most circulating RV strains in Egypt and evaluate it against the commercially available Rotarix® vaccine. Trial-IRVV was developed with 5% sucrose, 2% polysorbate-80, and adsorbed on Alum to potentiate the vaccine immune response. Then, it was injected subcutaneously into mice groups at 0-, 21-, and 35-time intervals. In parallel, Rotarix was administered twice on 0 and 28th day. The success of the pentavalent-IRVV/monovalent-Rotarix vaccine immunity rested on achieving immunoglobulin G (IgG) exceeding 1:6,400 that implies less susceptibility to RV infection (RVI). IRVV stimulating IgG >1:6,400 could be an alternative vaccination approach to reach a reasonable protective immunization level against RVI. In addition, Alum adjuvant incorporation effectively provoked a triple elevation of the immunization pattern.

  14. Epstein-Barr virus vaccine development: a lytic and latent protein cocktail.

    Science.gov (United States)

    Lockey, Timothy D; Zhan, Xiaoyan; Surman, Sherri; Sample, Clare E; Hurwitz, Julia L

    2008-05-01

    Epstein-Barr Virus (EBV) is the causative agent of acute infectious mononucleosis and associates with malignancies such as Burkitt lymphoma, nasopharyngeal carcinoma, and non-Hodgkin's lymphoma. Additionally, EBV is responsible for B-lymphoproliferative disease in the context of HIV-infection, genetic immunodeficiencies and organ/stem-cell transplantation. Here we discuss past and current efforts to design an EBV vaccine. We further describe preliminary studies of a novel cocktail vaccine expressing both lytic and latent EBV proteins. Specifically, a tetrameric vaccinia virus (VV) -based vaccine was formulated to express the EBV lytic proteins gp350 and gp110, and the latent proteins EBNA-2 and EBNA-3C. In a proof-of-concept study, mice were vaccinated with the individual or mixed VV. Each of the passenger genes was expressed in vivo at levels sufficient to elicit binding antibody responses. Neutralizing gp350-specific antibodies were also elicited, as were EBV-specific T-cell responses, following inoculation of mice with the single or mixed VV. Results encourage further development of the cocktail vaccine strategy as a potentially powerful weapon against EBV infection and disease in humans.

  15. Developing vaccines against foot-and-mouth disease and some other exotic viral diseases of livestock.

    Science.gov (United States)

    Paton, David J; Taylor, Geraldine

    2011-10-12

    Vaccines remain the main tool for the control of livestock viral diseases that pose a serious threat to animal and occasionally human health, reduce food security, distort trade in animals and their products, and undermine agricultural development in poor countries. Globalization and climate change increase the likelihood for new patterns of emergence and spread of livestock viruses. Conventionally attenuated and killed virus products have had spectacular success, and recent examples include the global eradication of rinderpest and the control of bluetongue in the UK and northern Europe. However, in many cases, livestock vaccines could benefit from improvement in some properties (e.g. stability, speed of onset and duration of immunity, and breadth of cross-protection to different serotypes or strains) and in some cases are not available at all. Compared with human vaccines, uptake of livestock products is highly cost-sensitive and their use may also need to be compatible with post-vaccination screening methods to determine whether or not animals continue to be infected. Requirements and prospects for new or improved vaccines are described for some priority viral diseases with potential for transboundary spread, particularly for foot-and-mouth disease.

  16. Pre-clinical development of a hydrogen peroxide-inactivated West Nile virus vaccine.

    Science.gov (United States)

    Poore, Elizabeth A; Slifka, Dawn K; Raué, Hans-Peter; Thomas, Archana; Hammarlund, Erika; Quintel, Benjamin K; Torrey, Lindsay L; Slifka, Ariel M; Richner, Justin M; Dubois, Melissa E; Johnson, Lawrence P; Diamond, Michael S; Slifka, Mark K; Amanna, Ian J

    2017-01-05

    West Nile virus (WNV) is a mosquito-transmitted pathogen with a wide geographical range that can lead to long-term disability and death in some cases. Despite the public health risk posed by WNV, including an estimated 3 million infections in the United States alone, no vaccine is available for use in humans. Here, we present a scaled manufacturing approach for production of a hydrogen peroxide-inactivated whole virion WNV vaccine, termed HydroVax-001WNV. Vaccination resulted in robust virus-specific neutralizing antibody responses and protection against WNV-associated mortality in mice or viremia in rhesus macaques (RM). A GLP-compliant toxicology study performed in rats demonstrated an excellent safety profile with clinical findings limited to minor and transient irritation at the injection site. An in vitro relative potency (IVRP) assay was developed and shown to correlate with in vivo responses following forced degradation studies. Long-term in vivo potency comparisons between the intended storage condition (2-8°C) and a thermally stressed condition (40±2°C) demonstrated no loss in vaccine efficacy or protective immunity over a 6-month span of time. Together, the positive pre-clinical findings regarding immunogenicity, safety, and stability indicate that HydroVax-001WNV is a promising vaccine candidate. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Role of men in promoting the uptake of HPV vaccinations: focus groups' finding from a developing country.

    Science.gov (United States)

    Wong, Li Ping

    2010-02-01

    Better outcomes of human papillomavirus (HPV) vaccination would be expected if men become full partners and advocates in vaccination initiative. Men involvement has important implication especially within the context that they are equally responsible for spreading the virus. Twenty-seven men took part in four focus group discussions carried out to assess men's attitudes toward the HPV vaccine between October and November 2007. The results revealed that men have low awareness about the newly release vaccine and minimal knowledge of HPV and its association with cervical cancer. When provided with information, most men were in favor of protecting their spouses, partners, or daughters from cervical cancer using the vaccine. They were aware of the effects of men's risk behavioral patterns on women's risk for acquiring HPV infections. Many needed assurance about the vaccine's long-term safety and efficacy. They also expressed concern over the high cost of the vaccine. Men in this study played an influential role in the vaccination decision of their child and sexual partners. Many were in favor of male vaccination for cervical cancer prevention of their spouse or partner. Vaccine advocacy should put special emphasis on men as sexual partners, husbands, and fathers from a gender equality and partnership perspective. The findings are useful in facilitating the development of strategies for effective immunization initiatives.

  18. The receptor binding domain of MERS-CoV: The dawn of vaccine and treatment development

    Directory of Open Access Journals (Sweden)

    Nan Zhou

    2014-03-01

    Full Text Available The newly emerged Middle East respiratory syndrome coronavirus (MERS-CoV is becoming another “SARS-like” threat to the world. It has an extremely high death rate (∼50% as there is no vaccine or efficient therapeutics. The identification of the structures of both the MERS-CoV receptor binding domain (RBD and its complex with dipeptidyl peptidase 4 (DPP4, raises the hope of alleviating this currently severe situation. In this review, we examined the molecular basis of the RBD-receptor interaction to outline why/how could we use MERS-CoV RBD to develop vaccines and antiviral drugs.

  19. Vector Development for the Expression of Foreign Proteins in the Vaccine Strain Brucella abortus S19

    Science.gov (United States)

    Comerci, Diego J.; Pollevick, Guido D.; Vigliocco, Ana M.; Frasch, Alberto C. C.; Ugalde, Rodolfo A.

    1998-01-01

    A vector for the expression of foreign antigens in the vaccine strain Brucella abortus S19 was developed by using a DNA fragment containing the regulatory sequences and the signal peptide of the Brucella bcsp31 gene. This fragment was cloned in broad-host-range plasmid pBBR4MCS, resulting in plasmid pBEV. As a reporter protein, a repetitive antigen of Trypanosoma cruzi was used. The recombinant fusion protein is stably expressed and secreted into the Brucella periplasmic space, inducing a good antibody response against the T. cruzi antigen. The expression of the repetitive antigen in Brucella neither altered its growth pattern nor generated a toxic or lethal effect during experimental infection. The application of this strategy for the generation of live recombinant vaccines and the tagging of B. abortus S19 vaccine is discussed. This is the first time that a recombinant protein has been expressed in the periplasm of brucellae. PMID:9673273

  20. The role of Plasmodium falciparum variant surface antigens in protective immunity and vaccine development

    DEFF Research Database (Denmark)

    Hviid, Lars

    2010-01-01

    that development of PfEMP1-based vaccines to protect specifically against severe malaria syndromes-in particular PAM-is feasible. This review summarizes the evidence that VSAs are important targets of NAI, discusses why VSA-based vaccines might be feasible despite the extensive intra- and interclonal variation...... of VSAs, and how vaccines based on this type of antigens fit into the current global strategy to reduce, eliminate and eventually eradicate the burden of malaria.......There is substantial immuno-epidemiological evidence that the parasite-encoded, so-called variant surface antigens (VSAs), such as PfEMP1 on the surface of infected erythrocytes (IEs) are important-in some cases probably decisive determinants of clinical outcome of P. falciparum malaria...

  1. Development of malaria transmission-blocking vaccines: from concept to product.

    Science.gov (United States)

    Wu, Yimin; Sinden, Robert E; Churcher, Thomas S; Tsuboi, Takafumi; Yusibov, Vidadi

    2015-06-01

    Despite decades of effort battling against malaria, the disease is still a major cause of morbidity and mortality. Transmission-blocking vaccines (TBVs) that target sexual stage parasite development could be an integral part of measures for malaria elimination. In the 1950s, Huff et al. first demonstrated the induction of transmission-blocking immunity in chickens by repeated immunizations with Plasmodium gallinaceum-infected red blood cells. Since then, significant progress has been made in identification of parasite antigens responsible for transmission-blocking activity. Recombinant technologies accelerated evaluation of these antigens as vaccine candidates, and it is possible to induce effective transmission-blocking immunity in humans both by natural infection and now by immunization with recombinant vaccines. This chapter reviews the efforts to produce TBVs, summarizes the current status and advances and discusses the remaining challenges and approaches. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. The role of Plasmodium falciparum variant surface antigens in protective immunity and vaccine development

    DEFF Research Database (Denmark)

    Hviid, Lars

    2010-01-01

    that development of PfEMP1-based vaccines to protect specifically against severe malaria syndromes-in particular PAM-is feasible. This review summarizes the evidence that VSAs are important targets of NAI, discusses why VSA-based vaccines might be feasible despite the extensive intra- and interclonal variation...... of VSAs, and how vaccines based on this type of antigens fit into the current global strategy to reduce, eliminate and eventually eradicate the burden of malaria.......There is substantial immuno-epidemiological evidence that the parasite-encoded, so-called variant surface antigens (VSAs) such as PfEMP1 on the surface of infected erythrocytes (IEs) are important-in some cases probably decisive-determinants of clinical outcome of P. falciparum malaria...

  3. Western blot assay for quantitative and qualitative antigen detection in vaccine development.

    Science.gov (United States)

    Kumar, Sanjai; Zheng, Hong; Mahajan, Babita; Kozakai, Yukiko; Morin, Merribeth; Locke, Emily

    2014-05-01

    Immunological methods for quantitative measurement, antigenic characterization, and monitoring the stability of active immunogenic component(s) are a critical need in the vaccine development process. This unit describes an enhanced chemiluminescence-based western blot for quantitative detection of Plasmodium falciparum circumsporozoite protein (PfCSP), a major malaria candidate vaccine antigen. The most salient features of this assay are its high sensitivity and reproducibility; it can reliably detect ∼5 to 10 pg PfCSP expressed on native parasites or recombinantly expressed in Escherichia coli. Although described for a specific vaccine antigen, this assay should be applicable for any antigen-antibody combination for which relevant detection reagents are available. Detailed stepwise experimental procedures and methods for data acquisition and analysis are described. Copyright © 2014 John Wiley & Sons, Inc.

  4. Maximizing protection from use of oral cholera vaccines in developing country settings

    Science.gov (United States)

    Desai, Sachin N; Cravioto, Alejandro; Sur, Dipika; Kanungo, Suman

    2014-01-01

    When oral vaccines are administered to children in lower- and middle-income countries, they do not induce the same immune responses as they do in developed countries. Although not completely understood, reasons for this finding include maternal antibody interference, mucosal pathology secondary to infection, malnutrition, enteropathy, and previous exposure to the organism (or related organisms). Young children experience a high burden of cholera infection, which can lead to severe acute dehydrating diarrhea and substantial mortality and morbidity. Oral cholera vaccines show variations in their duration of protection and efficacy between children and adults. Evaluating innate and memory immune response is necessary to understand V. cholerae immunity and to improve current cholera vaccine candidates, especially in young children. Further research on the benefits of supplementary interventions and delivery schedules may also improve immunization strategies. PMID:24861554

  5. Clinical development of a VAR2CSA-based placental malaria vaccine PAMVAC

    DEFF Research Database (Denmark)

    Gbédandé, Komi; Fievet, Nadine; Viwami, Firmine

    2017-01-01

    Background  The antigen VAR2CSA plays a pivotal role in the pathophysiology of pregnancy-associated malaria (PAM) caused by Plasmodium falciparum. A VAR2CSA-based vaccine candidate, PAMVAC, is under development by an EU-funded multi-country consortium (PlacMalVac project). As part of PAMVAC...

  6. Highlights of the 11th International Bordetella Symposium: from Basic Biology to Vaccine Development.

    Science.gov (United States)

    Carbonetti, Nicholas H; Wirsing von König, Carl Heinz; Lan, Ruiting; Jacob-Dubuisson, Francoise; Cotter, Peggy A; Deora, Rajendar; Merkel, Tod J; van Els, Cécile A; Locht, Camille; Hozbor, Daniela; Rodriguez, Maria E

    2016-11-01

    Pertussis is a severe respiratory disease caused by infection with the bacterial pathogen Bordetella pertussis The disease affects individuals of all ages but is particularly severe and sometimes fatal in unvaccinated young infants. Other Bordetella species cause diseases in humans, animals, and birds. Scientific, clinical, public health, vaccine company, and regulatory agency experts on these pathogens and diseases gathered in Buenos Aires, Argentina from 5 to 8 April 2016 for the 11th International Bordetella Symposium to discuss recent advances in our understanding of the biology of these organisms, the diseases they cause, and the development of new vaccines and other strategies to prevent these diseases. Highlights of the meeting included pertussis epidemiology in developing nations, genomic analysis of Bordetella biology and evolution, regulation of virulence factor expression, new model systems to study Bordetella biology and disease, effects of different vaccines on immune responses, maternal immunization as a strategy to prevent newborn disease, and novel vaccine development for pertussis. In addition, the group approved the formation of an International Bordetella Society to promote research and information exchange on bordetellae and to organize future meetings. A new Bordetella.org website will also be developed to facilitate these goals. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  7. Implications of differential age distribution of disease-associated meningococcal lineages for vaccine development

    NARCIS (Netherlands)

    Brehony, Carina; Trotter, Caroline L.; Ramsay, Mary E.; Chandra, Manosree; Jolley, Keith A.; van der Ende, Arie; Carion, Françoise; Berthelsen, Lene; Hoffmann, Steen; Harðardóttir, Hjördís; Vazquez, Julio A.; Murphy, Karen; Toropainen, Maija; Caniça, Manuela; Ferreira, Eugenia; Diggle, Mathew; Edwards, Giles F.; Taha, Muhamed-Kheir; Stefanelli, Paola; Kriz, Paula; Gray, Steve J.; Fox, Andrew J.; Jacobsson, Susanne; Claus, Heike; Vogel, Ulrich; Tzanakaki, Georgina; Heuberger, Sigrid; Caugant, Dominique A.; Frosch, Matthias; Maiden, Martin C. J.

    2014-01-01

    New vaccines targeting meningococci expressing serogroup B polysaccharide have been developed, with some being licensed in Europe. Coverage depends on the distribution of disease-associated genotypes, which may vary by age. It is well established that a small number of hyperinvasive lineages account

  8. The Historical Development of Vaccine Technology: Exploring the Relationship between Science and Technology

    Science.gov (United States)

    Lee, Yeung Chung; Kwok, Ping Wai

    2017-01-01

    This paper examines the feasibility of using historical case studies to contextualise the learning of the nature of science and technology in a biology lesson. Through exploring the historical development of vaccine technology, students were expected to understand the complexity of the relationships between technology and science beyond the…

  9. Development and Characterization of recA Mutants of Campylobacter jejuni for Inclusion in Attenuated Vaccines

    Science.gov (United States)

    1994-02-01

    993. ol-o936 tinuet Nach .amkin, M. J. Blaser, and L. S. Tompkins (ed.), Campylobacier C~ampylobacterjejuni in the initiation of Guillain - Barre syndrome...colitis, reactive arthritis, and Guillain - An alternative approach to enteric vaccines is the develop- Barr6 syndrome (5. 36). An estimated 400 million

  10. Development of a nanoparticle vaccine for a major killer of cattle ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    2018-01-12

    Jan 12, 2018 ... Developing an innovative solution. This highly innovative project combines current knowledge on ECF immunity with cutting edge biotechnology to formulate a vaccine that is expected to provide protection against ECF. Using protein engineering, immunomodulatory proteins will be blended with a parasite ...

  11. Use of formative research in developing a knowledge translation approach to rotavirus vaccine introduction in developing countries

    Directory of Open Access Journals (Sweden)

    Gamazina Kateryna

    2007-10-01

    Full Text Available Abstract Background Rotavirus gastroenteritis is the leading cause of diarrheal disease mortality among children under five, resulting in 450,000 to 700,000 deaths each year, and another 2 million hospitalizations, mostly in the developing world. Nearly every child in the world is infected with rotavirus at least once before they are five years old. Vaccines to prevent rotavirus or minimize its severity are now becoming available, and have already been introduced into the public vaccine programs of several Latin American countries. The World Health Organization (WHO has made rotavirus vaccine introduction in developing countries a high priority. The WHOs Guidelines for Vaccine Introduction indicates that a key determinant to achieving vaccine introduction is the public health priority of the disease, suggesting that where the disease is not a priority uptake of the vaccine is unlikely. WHO recommends conducting a qualitative analysis of opinions held by the public health community to determine the perceptions of the disease and the priority given to the vaccine. Methods This paper presents the formative research results of a qualitative survey of public health providers in five low- and middle-income countries to determine if and to what degree rotavirus is perceived to be a problem and the priority of a vaccine. Open-ended surveys were carried out through focus group discussions and one-on-one interviews. Results Researchers discovered that in all five countries knowledge of rotavirus was extremely low, and as a result was not considered a high priority. However, diarrhea among young children was considered a high priority among public health providers in the three poorest countries with relatively high levels of child mortality: India, Indonesia, and Nicaragua. Conclusion In the poorest countries, advocacy and communication efforts to raise awareness about rotavirus sufficient for prioritization and accelerated vaccine introduction might

  12. Development of fowl cholera vaccine: I. Protection of Pasteurella multocida local isolate vaccine against challenge of homologous and heterologous strains.

    Directory of Open Access Journals (Sweden)

    Supar

    2001-03-01

    Full Text Available Pasteurella multocida locally isolated from chicken and ducks (BCC 299, BCC 2331, DY1, DY2, 12TG, 15TG andimported strains (BCC 1359, 1362; HEDDLESTON group 1 and 6 respectively had been tested for its pathogenicity in theprevious study. The aims of this experiment were to study the preparation of local isolate pasteurellosis vaccines and to determine the protective effect of that vaccines in chicken against the highly pathogenic local isolates of P. multocida. Killed monovalent, bivalent and polyvalent pasteurellosis vaccines were prepared and each was adjunvanted with aluminum hydroxide gel at a final concentration of 1.5% and the cell concentration was equal to the No 10 of MacFarland tube standard. Each of the vaccine prepared was used to vaccinated on a group of six week old of layer chicken (8 per group. Each chicken was subcutaneously injected with 0.2 ml of vaccine, four weeks later each was boostered with similar vaccine with the same dose. Two weeks after giving the boostered vaccine each group of chicken were challenged, half with life bacterium of P. Multocida BCC 2331 and other with DY2. Any chick which survive after challenge was designated as protected by vaccination. Before vaccination 1 ml of blood was drawn from each of chicken and then two weeks apart up to challenge. Serum from each sample was separated and kept in deep freeze until tested by enzyme-linked immunosorbent assay (ELISA. Chicken vaccinated with killed whole cell P. multocida vaccines of monovalent (BCC 2331 or DY2 and bivalent (BCC 2331 + DY2 were protected against challenge with live bacterium of either BCC 2331 or DY2 at rate 67-100%. There was no protection in chicken vaccinated with either BCC 299, DY1, 12TG, 15TG, BCC 1359, or 1362 killed vaccine. Similarly no protection of chicken vaccinated with either DY1 + BCC299, 12TG + 15TG or BCC 1359 + BCC 1362 bivalent vaccines. The protection rate of the polyvalent local isolate vaccine was at average 50-75%. All

  13. Trained immunity: a new avenue for tuberculosis vaccine development.

    Science.gov (United States)

    Lerm, M; Netea, M G

    2016-04-01

    Adaptive immunity towards tuberculosis (TB) has been extensively studied for many years. In addition, in recent years the profound contribution of innate immunity to host defence against this disease has become evident. The discovery of pattern recognition receptors, which allow innate immunity to tailor its response to different infectious agents, has challenged the view that this arm of immunity is nonspecific. Evidence is now accumulating that innate immunity can remember a previous exposure to a microorganism and respond differently during a second exposure. Although the specificity and memory of innate immunity cannot compete with the highly sophisticated adaptive immune response, its contribution to host defence against infection and to vaccine-induced immunity should not be underestimated and needs to be explored. Here, we present the concept of trained immunity and discuss how this may contribute to new avenues for control of TB. © 2015 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.

  14. Development of a vaccine to mitigate greenhouse gas emissions in agriculture: vaccination of sheep with methanogen fractions induces antibodies that block methane production in vitro.

    Science.gov (United States)

    Wedlock, D N; Pedersen, G; Denis, M; Dey, D; Janssen, P H; Buddle, B M

    2010-02-01

    To develop an understanding of the immune responses of ruminants to methanogens, and to provide proof of a concept that harnessing the immune system of ruminants is a potentially viable approach to mitigate greenhouse gas emissions from agriculture. Four subcellular fractions, namely cytoplasmic, two cell-wall preparations, and cell wall-derived proteins were prepared from Methanobrevibacter ruminantium M1. Twenty sheep (10 months of age) were vaccinated with these fractions or with whole cells (n=4 per group). Sheep were re-vaccinated once after 3 weeks, and antibody responses to M. ruminantium M1 antigens in sera and saliva measured using ELISA at 2 weeks after the second vaccination. Antigens recognised by the antisera were visualised using Western blotting. The antisera were tested in vitro for their impact on M. ruminantium M1, measuring the effect on cell growth, methane production, and ability to induce agglutination. Basal levels (pre-vaccination) of antibodies against M. ruminantium M1 antigens were low. Vaccination with the antigenic fractions induced strong antibody responses in serum. Both IgG and IgA responses to methanogen antigens were detected in saliva following vaccination. Western blot analysis of the antisera indicated reactivity of antibodies, and a wide range of proteins was present in the different methanogen fractions. Antisera against the various fractions agglutinated methanogens in an in-vitro assay. In addition, these antisera decreased the growth of a pure culture of a methanogen and production of methane in vitro. Antigens from methanogens are immunogenic in ruminants, and antisera from sheep vaccinated with fractions of methanogens have a significant impact on these organisms, inducing cell agglutination, and decreasing growth of methanogens and production of methane. Only antisera to selected methanogen fractions were able to achieve these effects. The results demonstrate the feasibility of a vaccination strategy to mitigate emission

  15. How to develop a program to increase influenza vaccine uptake among workers in health care settings?

    Directory of Open Access Journals (Sweden)

    van Delden Johan JM

    2011-05-01

    Full Text Available Abstract Background Apart from direct protection and reduced productivity loss during epidemics, the main reason to immunize healthcare workers (HCWs against influenza is to provide indirect protection of frail patients through reduced transmission in healthcare settings. Because the vaccine uptake among HCWs remains far below the health objectives, systematic programs are needed to take full advantage of such vaccination. In an earlier report, we showed a mean 9% increase of vaccine uptake among HCWs in nursing homes that implemented a systematic program compared with control homes, with higher rates in those homes that implemented more program elements. Here, we report in detail the process of the development of the implementation program to enable researchers and practitioners to develop intervention programs tailored to their setting. Methods We applied the intervention mapping (IM method to develop a theory- and evidence-based intervention program to change vaccination behaviour among HCWs in nursing homes. Results After a comprehensive needs assessment, we were able to specify proximal program objectives and selected methods and strategies for inducing behavioural change. By consensus, we decided on planning of three main program components, i.e., an outreach visit to all nursing homes, plenary information meetings, and the appointment of a program coordinator -- preferably a physician -- in each home. Finally, we planned program adoption, implementation, and evaluation. Conclusion The IM methodology resulted in a systematic, comprehensive, and transparent procedure of program development. A potentially effective intervention program to change influenza vaccination behaviour among HCWs was developed, and its impact was assessed in a clustered randomised controlled trial.

  16. Molecular Basis of Allele-Specific Efficacy of a Blood-Stage Malaria Vaccine: Vaccine Development Implications

    Science.gov (United States)

    Ouattara, Amed; Takala-Harrison, Shannon; Thera, Mahamadou A.; Coulibaly, Drissa; Niangaly, Amadou; Saye, Renion; Tolo, Youssouf; Dutta, Sheetij; Heppner, D. Gray; Soisson, Lorraine; Diggs, Carter L.; Vekemans, Johan; Cohen, Joe; Blackwelder, William C.; Dube, Tina; Laurens, Matthew B.; Doumbo, Ogobara K.; Plowe, Christopher V.

    2013-01-01

    The disappointing efficacy of blood-stage malaria vaccines may be explained in part by allele-specific immune responses that are directed against polymorphic epitopes on blood-stage antigens. FMP2.1/AS02A, a blood-stage candidate vaccine based on apical membrane antigen 1 (AMA1) from the 3D7 strain of Plasmodium falciparum, had allele-specific efficacy against clinical malaria in a phase II trial in Malian children. We assessed the cross-protective efficacy of the malaria vaccine and inferred which polymorphic amino acid positions in AMA1 were the targets of protective allele-specific immune responses. FMP2.1/AS02A had the highest efficacy against AMA1 alleles that were identical to the 3D7 vaccine-type allele at 8 highly polymorphic amino acid positions in the cluster 1 loop (c1L) but differed from 3D7 elsewhere in the molecule. Comparison of the incidence of vaccine-type alleles before and after vaccination in the malaria vaccine and control groups and examination of the patterns of allele change at polymorphic positions in consecutive malaria episodes suggest that the highly polymorphic amino acid position 197 in c1L was the most critical determinant of allele-specific efficacy. These results indicate that a multivalent AMA1 vaccine with broad efficacy could include only a limited set of key alleles of this extremely polymorphic antigen. PMID:23204168

  17. Development of apple latent spherical virus-based vaccines against three tospoviruses.

    Science.gov (United States)

    Taki, Ayano; Yamagishi, Noriko; Yoshikawa, Nobuyuki

    2013-09-01

    Apple latent spherical virus (ALSV) is characterized by its relatively broad host range, latency in most host plants, and ability to induce gene silencing in host plants. Herein, we focus on the above characteristic of ALSV and describe our development of ALSV vector vaccines against three tospoviruses, namely, Impatiens necrotic spot virus (INSV), Iris yellow spot virus (IYSV), and Tomato spotted wilt virus (TSWV). DNA fragments of 201 nt of three tospovirus S-RNAs (silencing suppressor (NSS) and nucleocapsid protein (N) coding regions for each tospovirus) were inserted into an ALSV-RNA2 vector to obtain six types of ALSV vector vaccines. Nicotiana benthamiana plants at the five-leaf stage were inoculated with each ALSV vector vaccine and challenged with the corresponding tospovirus species. Tospovirus-induced symptoms and tospovirus replication after challenge were significantly suppressed in plants preinoculated with all ALSV vector vaccines having the N region fragment, indicating that strong resistance was acquired after infection with ALSV vector vaccines. On the other hand, cross protection was not significant in plants preinoculated with ALSV vectors having the NSs region fragment. Similarly, inoculation with an ALSV-RNA1 vector having the N region fragment in the 3'-noncoding region, but not the NSs region fragment, induced cross protection, indicating that cross protection is via RNA silencing, not via the function of the protein derived from the N region fragment. Our approach, wherein ALSV vectors and selected target inserts are used, enables rapid establishment of ALSV vector vaccines against many pathogenic RNA viruses with known sequences. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. Development and evaluation of a novel subunit vaccine for Mycoplasma gallisepticum

    Directory of Open Access Journals (Sweden)

    L. Moura

    2012-12-01

    Full Text Available Adhesion proteins from Mycoplasma gallisepticum (MG encoded by cytadhesion genes mgc1 and mgc2 were cloned into plasmid vectors and transformed into E. coli. Seventeen groups of specific-pathogen free (SPF, birds at four weeks of age were used to inoculate these two proteins (MGC1 and MGC2 mixed into an oil emulsion creating a novel MG vaccine. Six different protein concentrations (50, 100, 200, 400, 800, and 1000µg/bird were tested with two equal concentration doses at four and seven weeks of age. In addition, many control groups were needed such as bacterin, membrane, no vaccine or challenge, oil emulsion alone, and no vaccine but challenged. Three weeks following the second vaccination, 50% of the birds in each treatment group were challenged with MG strain S6. The remaining birds were left as contacts to verify protection against horizontal transmission. All birds were bled before vaccinations, challenge and euthanasia. Birds were negative for MG at the first vaccination, as shown by serum plate agglutination test. At necropsy, tissue samples (trachea, lungs, and air sacs were collected for histopathological examination. Swabs from trachea were used for PCR analysis. ELISA results showed a strong immune response to both protein preparations and almost the same response level for different doses tested, proving the immunogenic features of MGC1 and MGC2. However, humoral responses failed to prevent MG infection and disease when challenged as demonstrated by PCR and histopathology. MGC1 contact birds showed some degree of infection by PCR analysis. In addition, histopathological and ELISA results suggest that contact birds did not have enough time to develop lesions and to mount an immune response.

  19. Development and Preclinical Evaluation of a Trivalent, Formalin-Inactivated Shigella Whole-Cell Vaccine

    Science.gov (United States)

    Kaminski, R. W.; Wu, M.; Turbyfill, K. R.; Clarkson, K.; Tai, B.; Bourgeois, A. L.; Van De Verg, L. L.; Walker, R. I.

    2014-01-01

    Studies were undertaken to manufacture a multivalent Shigella inactivated whole-cell vaccine that is safe, effective, and inexpensive. By using several formalin concentrations, temperatures, and incubation periods, an optimized set of inactivation conditions was established for Shigella flexneri 2a, S. sonnei, and S. flexneri 3a to produce inactivated whole cells expressing a full repertoire of Ipa proteins and lipopolysaccharide (LPS). The inactivation conditions selected were treatment with 0.2% formalin (S. flexneri 2a and 3a) or 0.6% formalin (S. sonnei) for 48 h at 25°C. Vaccine formulations prepared under different inactivation conditions, in different doses (10E5, 10E7, and 10E9 cells), and with or without the inclusion of double-mutant heat-labile toxin (dmLT) were evaluated in mice. Two intranasal immunizations with ≥10E7 inactivated whole cells resulted in high levels of anti-Invaplex and moderate levels of LPS-specific IgG and IgA in serum and in lung and intestinal wash samples. Addition of dmLT to the vaccine formulations did not significantly enhance humoral immunogenicity. Minimal humoral responses for IpaB, IpaC, or IpaD were detected after immunization with inactivated whole Shigella cells regardless of the vaccine inactivation conditions. In guinea pigs, monovalent formulations of S. flexneri 2a of 3a or S. sonnei consisting of 10E8, 10E9, or 10E10 cells were protective in a keratoconjunctivitis assay. A trivalent formulation provided protection against all three serotypes (S. flexneri 2a, P = 0.018; S. flexneri 3a, P = 0.04; S. sonnei, P inactivated Shigella whole-cell vaccine approach incorporates an uncomplicated manufacturing process that is compatible with multivalency and the future development of a broadly protective Shigella vaccine. PMID:24403527

  20. Green revolution vaccines, edible vaccines | Tripurani | African ...

    African Journals Online (AJOL)

    ... cholera, hepatitis-B, and many more are in the process of development. Food vaccines may also help to suppress autoimmunity disorders such as Type-1 Diabetes. Key words: Edible vaccines, oral vaccines, antigen expression, food vaccines. African Journal of Biotechnology Vol. 2 (12), pp. 679-683, December 2003 ...

  1. New strategies for immune-mediated anti-viral drug and vaccine development.

    Science.gov (United States)

    Chen, Chiann-Chyi; Ron, Yacov

    2006-01-01

    Substantial progress in the development of new anti-viral drugs has taken place in recent years. Most of these new drugs belong to three groups of compounds, nucleoside analogs, thymidine kinase-dependent nucleotide analogs and specific viral enzyme inhibitors. Although these drugs revolutionized the treatment of several viral diseases, the involvement of the immune system is crucial for complete recovery and prevention of re-infection. New advances in the understanding of immune regulation mechanisms, mainly the role of cytokines, led to the development of several new immunologically-based anti-viral drugs and treatments. The most studied group of immunomodulators is the cytokines, some of which were shown to act as potent stimulators of immune responses. Other, non-cytokine immune modulators have also been successfully employed in both humans and experimental animals as anti-viral drugs of which several are currently in clinical trials. Advances in genetic engineering and transgenic mouse technologies facilitated the production of humanized as well as authentic human anti-viral monoclonal antibodies. Some of these antibodies proved to be clinically efficacious and are commercially produced as anti-viral drugs. As is often the case in anti-viral treatments, a combination of conventional and an immune-mediated anti-viral drugs or a combination therapy involving immunomodulators, therapeutic vaccines, immune intervention and even gene therapy might prove most efficacious as a treatment for a particular virus. Most of the advances made in anti-viral treatments have also been applied to the development of new vaccines. Some of the classical attenuated viruses are being replaced by recombinant attenuated viruses. Recombinant viral vaccines containing genes encoding other viral antigens and/or cytokines are being tested as new vaccines. Several chimeric viral vaccines have proven efficacious in experimental animals and are now in different phases of clinical trials

  2. The Development of Vaccination Perspectives among Chiropractic, Naturopathic and Medical Students: A Case Study of Professional Enculturation

    Science.gov (United States)

    McMurtry, Angus; Wilson, Kumanan; Clarkin, Chantalle; Walji, Rishma; Kilian, Brendan C.; Kilian, Carney C.; Lohfeld, Lynne; Alolabi, Bashar; Hagino, Carol; Busse, Jason W.

    2015-01-01

    An important influence on parents' decisions about pediatric vaccination (children under 6 years of age) is the attitude of their health care providers, including complementary and alternative medicine (CAM) providers. Very limited qualitative research exists, however, on how attitudes towards vaccination develop among healthcare professionals…

  3. History of vaccination

    OpenAIRE

    Plotkin, Stanley

    2014-01-01

    Vaccines have a history that started late in the 18th century. From the late 19th century, vaccines could be developed in the laboratory. However, in the 20th century, it became possible to develop vaccines based on immunologic markers. In the 21st century, molecular biology permits vaccine development that was not possible before.

  4. History of vaccination.

    Science.gov (United States)

    Plotkin, Stanley

    2014-08-26

    Vaccines have a history that started late in the 18th century. From the late 19th century, vaccines could be developed in the laboratory. However, in the 20th century, it became possible to develop vaccines based on immunologic markers. In the 21st century, molecular biology permits vaccine development that was not possible before.

  5. Development of Virus-Like-Particle Vaccine and Reporter Assay for Zika Virus.

    Science.gov (United States)

    Garg, Himanshu; Sedano, Melina; Plata, Gabrielle; Punke, Erin B; Joshi, Anjali

    2017-10-15

    Recent worldwide outbreaks of Zika virus (ZIKV) infection and the lack of an approved vaccine raise serious concerns regarding preparedness to combat this emerging virus. We used a virus-like particle (VLP)-based approach to develop a vaccine and a microneutralization assay for ZIKV. A synthetic capsid-premembrane-envelope (C-prM-E) gene construct of ZIKV was used to generate reporter virus particles (RVPs) that package a green fluorescent protein (GFP) reporter-expressing West Nile virus (WNV) replicon. The assay was adapted to a 96-well format, similar to the plaque reduction neutralization test (PRNT), and showed high reproducibility with specific detection of ZIKV neutralizing antibodies. Furthermore, C-prM-E and prM-E VLPs were tested as vaccine candidates in mice and compared to DNA vaccination. While the ZIKV prM-E construct alone was sufficient for generating VLPs, efficient VLP production from the C-prM-E construct could be achieved in the presence of the WNV NS2B-3 protease, which cleaves C from prM, allowing virus release. Immunization studies in mice showed that VLPs generated higher neutralizing antibody titers than those with the DNA vaccines, with C-prM-E VLPs giving slightly higher titers than those with prM-E VLPs. The superiority of C-prM-E VLPs suggests that inclusion of capsid may have benefits for ZIKV and other flaviviral VLP vaccines. To facilitate the VLP platform, we generated a stable cell line expressing high levels of ZIKV prM-E proteins that constitutively produce VLPs as well as a cell line expressing ZIKV C-prM-E proteins for RVP production. While several vaccine platforms have been proposed for ZIKV, this study describes a safe, effective, and economical VLP-based vaccine against ZIKV.IMPORTANCE To address the growing Zika virus epidemic, we undertook this study with two objectives: first, to develop a safe, effective, and economical vaccine for ZIKV, and second, to develop a rapid and versatile assay to detect the anti-ZIKV immune

  6. Preclinical Development of an In Vivo BCG Challenge Model for Testing Candidate TB Vaccine Efficacy

    Science.gov (United States)

    Minassian, Angela M.; Ronan, Edward O.; Poyntz, Hazel; Hill, Adrian V. S.; McShane, Helen

    2011-01-01

    There is an urgent need for an immunological correlate of protection against tuberculosis (TB) with which to evaluate candidate TB vaccines in clinical trials. Development of a human challenge model of Mycobacterium tuberculosis (M.tb) could facilitate the detection of such correlate(s). Here we propose a novel in vivo Bacille Calmette-Guérin (BCG) challenge model using BCG immunization as a surrogate for M.tb infection. Culture and quantitative PCR methods have been developed to quantify BCG in the skin, using the mouse ear as a surrogate for human skin. Candidate TB vaccines have been evaluated for their ability to protect against a BCG skin challenge, using this model, and the results indicate that protection against a BCG skin challenge is predictive of BCG vaccine efficacy against aerosol M.tb challenge. Translation of these findings to a human BCG challenge model could enable more rapid assessment and down selection of candidate TB vaccines and ultimately the identification of an immune correlate of protection. PMID:21629699

  7. A review of reverse vaccinology approaches for the development of vaccines against ticks and tick borne diseases.

    Science.gov (United States)

    Lew-Tabor, A E; Rodriguez Valle, M

    2016-06-01

    The field of reverse vaccinology developed as an outcome of the genome sequence revolution. Following the introduction of live vaccinations in the western world by Edward Jenner in 1798 and the coining of the phrase 'vaccine', in 1881 Pasteur developed a rational design for vaccines. Pasteur proposed that in order to make a vaccine that one should 'isolate, inactivate and inject the microorganism' and these basic rules of vaccinology were largely followed for the next 100 years leading to the elimination of several highly infectious diseases. However, new technologies were needed to conquer many pathogens which could not be eliminated using these traditional technologies. Thus increasingly, computers were used to mine genome sequences to rationally design recombinant vaccines. Several vaccines for bacterial and viral diseases (i.e. meningococcus and HIV) have been developed, however the on-going challenge for parasite vaccines has been due to their comparatively larger genomes. Understanding the immune response is important in reverse vaccinology studies as this knowledge will influence how the genome mining is to be conducted. Vaccine candidates for anaplasmosis, cowdriosis, theileriosis, leishmaniasis, malaria, schistosomiasis, and the cattle tick have been identified using reverse vaccinology approaches. Some challenges for parasite vaccine development include the ability to address antigenic variability as well the understanding of the complex interplay between antibody, mucosal and/or T cell immune responses. To understand the complex parasite interactions with the livestock host, there is the limitation where algorithms for epitope mining using the human genome cannot directly be adapted for bovine, for example the prediction of peptide binding to major histocompatibility complex motifs. As the number of genomes for both hosts and parasites increase, the development of new algorithms for pan-genomic mining will continue to impact the future of parasite and

  8. Worldwide genetic variability of the Duffy binding protein: insights into Plasmodium vivax vaccine development.

    Directory of Open Access Journals (Sweden)

    Taís Nóbrega de Sousa

    Full Text Available The dependence of Plasmodium vivax on invasion mediated by Duffy binding protein (DBP makes this protein a prime candidate for development of a vaccine. However, the development of a DBP-based vaccine might be hampered by the high variability of the protein ligand (DBP(II, known to bias the immune response toward a specific DBP variant. Here, the hypothesis being investigated is that the analysis of the worldwide DBP(II sequences will allow us to determine the minimum number of haplotypes (MNH to be included in a DBP-based vaccine of broad coverage. For that, all DBP(II sequences available were compiled and MNH was based on the most frequent nonsynonymous single nucleotide polymorphisms, the majority mapped on B and T cell epitopes. A preliminary analysis of DBP(II genetic diversity from eight malaria-endemic countries estimated that a number between two to six DBP haplotypes (17 in total would target at least 50% of parasite population circulating in each endemic region. Aiming to avoid region-specific haplotypes, we next analyzed the MNH that broadly cover worldwide parasite population. The results demonstrated that seven haplotypes would be required to cover around 60% of DBP(II sequences available. Trying to validate these selected haplotypes per country, we found that five out of the eight countries will be covered by the MNH (67% of parasite populations, range 48-84%. In addition, to identify related subgroups of DBP(II sequences we used a Bayesian clustering algorithm. The algorithm grouped all DBP(II sequences in six populations that were independent of geographic origin, with ancestral populations present in different proportions in each country. In conclusion, in this first attempt to undertake a global analysis about DBP(II variability, the results suggest that the development of DBP-based vaccine should consider multi-haplotype strategies; otherwise a putative P. vivax vaccine may not target some parasite populations.

  9. Vaccinomics and personalized vaccinology: is science leading us toward a new path of directed vaccine development and discovery?

    Directory of Open Access Journals (Sweden)

    Gregory A Poland

    2011-12-01

    Full Text Available As is apparent in many fields of science and medicine, the new biology, and particularly new high-throughput genetic sequencing and transcriptomic and epigenetic technologies, are radically altering our understanding and views of science. In this article, we make the case that while mostly ignored thus far in the vaccine field, these changes will revolutionize vaccinology from development to manufacture to administration. Such advances will address a current major barrier in vaccinology-that of empiric vaccine discovery and development, and the subsequent low yield of viable vaccine candidates, particularly for hyper-variable viruses. While our laboratory's data and thinking (and hence also for this paper has been directed toward viruses and viral vaccines, generalization to other pathogens and disease entities (i.e., anti-cancer vaccines may be appropriate.

  10. Development of World Health Organization (WHO recommendations for appropriate clinical trial endpoints for next-generation Human Papillomavirus (HPV vaccines

    Directory of Open Access Journals (Sweden)

    Malavika Prabhu

    2016-12-01

    Full Text Available The World Health Organization (WHO serves as a key organization to bring together experts along the continuum of vaccine development and regulatory approval, among its other functions. Using the revision of WHO's guidelines on prophylactic human papillomavirus (HPV vaccine as an example, we describe the process by which (1 a need to revise the guidelines was identified; (2 a group of stakeholders with complementary expertise and key questions were identified; (3 a scientific review was conducted; (4 consensus on revisions was achieved; (5 guidelines were updated, reviewed widely, and approved. This multi-year process resulted in the consensus that regulatory agencies could consider additional endpoints, such as persistent HPV infection or immune equivalence, depending on the design of the HPV vaccine trials. Updating the guidelines will now accelerate vaccine development, reduce costs of clinical trials, and lead to faster regulatory approval. Keywords: HPV vaccine, WHO, Policy guidelines

  11. Deinococcus Mn(2+)-peptide complex: A novel approach to alphavirus vaccine development.

    Science.gov (United States)

    Gayen, Manoshi; Gupta, Paridhi; Morazzani, Elaine M; Gaidamakova, Elena K; Knollmann-Ritschel, Barbara; Daly, Michael J; Glass, Pamela J; Maheshwari, Radha K

    2017-06-22

    Over the last ten years, Chikungunya virus (CHIKV), an Old World alphavirus has caused numerous outbreaks in Asian and European countries and the Americas, making it an emerging pathogen of great global health importance. Venezuelan equine encephalitis virus (VEEV), a New World alphavirus, on the other hand, has been developed as a bioweapon in the past due to its ease of preparation, aerosol dispersion and high lethality in aerosolized form. Currently, there are no FDA approved vaccines against these viruses. In this study, we used a novel approach to develop inactivated vaccines for VEEV and CHIKV by applying gamma-radiation together with a synthetic Mn-decapeptide-phosphate complex (MnDpPi), based on manganous-peptide-orthophosphate antioxidants accumulated in the extremely radiation-resistant bacterium Deinococcus radiodurans. Classical gamma-irradiated vaccine development approaches are limited by immunogenicity-loss due to oxidative damage to the surface proteins at the high doses of radiation required for complete virus-inactivation. However, addition of MnDpPi during irradiation process selectively protects proteins, but not the nucleic acids, from the radiation-induced oxidative damage, as required for safe and efficacious vaccine development. Previously, this approach was used to develop a bacterial vaccine. In the present study, we show that this approach can successfully be applied to protecting mice against viral infections. Irradiation of VEEV and CHIKV in the presence of MnDpPi resulted in substantial epitope preservation even at supra-lethal doses of gamma-rays (50,000Gy). Irradiated viruses were found to be completely inactivated and safe in vivo (neonatal mice). Upon immunization, VEEV inactivated in the presence of MnDpPi resulted in drastically improved protective efficacy. Thus, the MnDpPi-based gamma-inactivation approach described here can readily be applied to developing vaccines against any pathogen of interest in a fast and cost

  12. Development of a transmission-blocking malaria vaccine: progress, challenges, and the path forward.

    Science.gov (United States)

    Nunes, Julia K; Woods, Colleen; Carter, Terrell; Raphael, Theresa; Morin, Merribeth J; Diallo, Diadier; Leboulleux, Didier; Jain, Sanjay; Loucq, Christian; Kaslow, David C; Birkett, Ashley J

    2014-09-29

    New interventions are needed to reduce morbidity and mortality associated with malaria, as well as to accelerate elimination and eventual eradication. Interventions that can break the cycle of parasite transmission, and prevent its reintroduction, will be of particular importance in achieving the eradication goal. In this regard, vaccines that interrupt malaria transmission (VIMT) have been highlighted as an important intervention, including transmission-blocking vaccines that prevent human-to-mosquito transmission by targeting the sexual, sporogonic, or mosquito stages of the parasite (SSM-VIMT). While the significant potential of this vaccine approach has been appreciated for decades, the development and licensure pathways for vaccines that target transmission and the incidence of infection, as opposed to prevention of clinical malaria disease, remain ill-defined. This article describes the progress made in critical areas since 2010, highlights key challenges that remain, and outlines important next steps to maximize the potential for SSM-VIMTs to contribute to the broader malaria elimination and eradication objectives. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  13. Towards clinical development of a Pfs48/45-based transmission blocking malaria vaccine.

    Science.gov (United States)

    Theisen, Michael; Jore, Matthijs M; Sauerwein, Robert

    2017-04-01

    Malaria is a devastating vector-borne disease caused by the Plasmodium parasite, resulting in almost 0.5 million casualties per year. The parasite has a complex life-cycle that includes asexual replication in human red blood cells, causing symptomatic malaria, and sexual stages which are essential for the transmission to the mosquito vector. A vaccine targeting the sexual stages of the parasite and thus blocking transmission will be instrumental for the eradication of malaria. One of the leading transmission blocking vaccine candidates is the sexual stage antigen Pfs48/45. Areas covered: PubMed was searched to review the progress and future prospects for clinical development of a Pfs48/45-based subunit vaccine. We will focus on biological function, naturally acquired immunity, functional activity of specific antibodies, sequence diversity, production of recombinant protein and preclinical studies. Expert commentary: Pfs48/45 is one of the lead-candidates for a transmission blocking vaccine and should be further explored in clinical trials.

  14. Isolation, Specification, Molecular Biology Assessment and Vaccine Development of Clostridium in Iran: A Review

    Directory of Open Access Journals (Sweden)

    Reza Pilehchian Langroudi

    2015-11-01

    Full Text Available Context: The genus Clostridium, which consists of spore-forming anaerobes, can cause different diseases in domestic animals and human and some of them are serious and fatal. According to the increasing economic value of the meat and milk-producing animals, the importance of a certain number of such diseases in Iran is unquestionable. Evidence Acquisition: In Iran, and probably in other Near East countries, much attention was formerly paid to control more serious contagious diseases, such as rinderpest, anthrax, etc. resulting in the negligence of diseases such as enterotoxaemia. The epizootiological position has now changed whereby some of the contagious diseases are eradicated or are being methodically controlled.Now it is time to care about the other problems such as clostridial diseases, which threaten the health of the sheep and cattle. It is impossible to eradicate these infectious microorganisms, since they are normally found in the soil and the intestinal contents of apparently healthy animals. Therefore, it is necessary to resort to vaccination which in some cases has given encouraging results. To avoid the losses from such infections it is necessary to have the best possible vaccination information, methodically and regularity of the susceptible animals. Conclusions: This review refers to the veterinary aspects of the anaerobic clostridial diseases and vaccine development concerning the works carried out in Iran and especially at the Razi Serum and Vaccine Research Institute in the last eight decades.

  15. Clinical development of plant-produced recombinant pharmaceuticals: vaccines, antibodies and beyond.

    Science.gov (United States)

    Yusibov, Vidadi; Streatfield, Stephen J; Kushnir, Natasha

    2011-03-01

    In the last few years, plants have become an increasingly attractive platform for recombinant protein production. This builds on two decades of research, starting with transgenic approaches to develop oral vaccines in which antigens or therapeutics can be delivered in processed plant biomass, and progressing to transient expression approaches whereby high yields of purified targets are administered parenterally. The advantages of plant-based expression systems include high scalability, low upstream costs, biocontainment, lack of human or animal pathogens, and ability to produce target proteins with desired structures and biological functions. Using transgenic and transient expression in whole plants or plant cell culture, a variety of recombinant subunit vaccine candidates, therapeutic proteins, including monoclonal antibodies, and dietary proteins have been produced. Some of these products have been tested in early phase clinical trials, and show safety and efficacy. Among those are mucosal vaccines for diarrheal diseases, hepatitis B and rabies; injectable vaccines for non-Hodgkin's lymphoma, H1N1 and H5N1 strains of influenza A virus, and Newcastle disease in poultry; and topical antibodies for the treatment of dental caries and HIV. As lead plant-based products have entered clinical trials, there has been increased emphasis on manufacturing under current Good Manufacturing Practice (cGMP) guidelines, and the preparation and presentation to the relevant government agencies of regulatory packages.

  16. Development of Autologous C5 Vaccine Nanoparticles to Reduce Intravascular Hemolysis in Vivo.

    Science.gov (United States)

    Zhang, Lingjun; Qiu, Wen; Crooke, Stephen; Li, Yan; Abid, Areeba; Xu, Bin; Finn, M G; Lin, Feng

    2017-02-17

    The complement system is emerging as a new target for treating many diseases. For example, Eculizumab, a humanized monoclonal antibody against complement component 5 (C5), has been approved for paroxysmal nocturnal hemoglobinuria (PNH) in which patient erythrocytes are lysed by complement. In this study, we developed vaccines to elicit autologous anti-C5 antibody production in mice for complement inhibition. Immunization of mice with a conservative C5 xenoprotein raised high titers of IgG's against the xenogenous C5, but these antibodies did not reduce C5 activity in the blood. In contrast, an autologous mouse C5 vaccine containing multiple predicted epitopes together with a tolerance-breaking peptide was found to induce anti-C5 autoantibody production in vivo, resulting in decreased hemolytic activity in the blood. We further validated a peptide epitope within this C5 vaccine and created recombinant virus-like particles (VLPs) displaying this epitope fused with the tolerance breaking peptide. Immunizing mice with these novel nanoparticles elicited strong humoral responses against recombinant mouse C5, reduced hemolytic activity, and protected the mice from complement-mediated intravascular hemolysis in a model of PNH. This proof-of-concept study demonstrated that autologous C5-based vaccines could be an effective alternative or supplement for treating complement-mediated diseases such as PNH.

  17. PERSPECTIVES OF THE DEVELOPMENT OF MUCOSAL VACCINES AGAINST DANGEROUS INFECTIONS ON THE BASE OF TRANSGENIC PLANTS

    Directory of Open Access Journals (Sweden)

    A.V. Tretyakova

    2012-08-01

    Full Text Available Mucosal vaccines created on the base of transgenic plants reacting with mucosal layers of the intestines and other organs are considered to be the perspective method of the vaccination. These vaccines induce both mucosal and general humoral immunogenicity after the peroral administration. The folding of antigenic proteins synthesizing in plants occurs via eukaryotic type and has advantages before yeast and prokaryotic platforms. This feature results to more adequate synthesis of antibodies against pathogens and to the interaction with effector molecules of complement. Earlier we together with The State Scientific Center “Vector”, Institute of chemical biology and fundamental medicine SB RAS and Dr R.Hammond from Laboratory of Plant Pathology (Maryland, USA created two candidate vaccines : one of them against AIDS (HIV-1 and hepatitis B on the base of the chimeric gene TBI-HBS, encoding simultaneously 9 antigenic determinants of HIV-1 and the main surface antigen of hepatitis B (HBsAg. The second candidate vaccine was created against hepatitis B on the base of the genetic construct with the gene preS2-S encoding the synthesis of two subunits of the main surface antigen of hepatitis B and the signal peptide HDEL which directed antigens for the accumulation on ER. Both vaccines were tested on mice and confirmed their immunogenicity as the pronounced antibodies response. Twice vaccinated mice maintained the antibodies response during 11 months after there was little tendency to lowering. It was established that transgenic plants – vaccines (tomato kept the capability to the synthesis of antigenic determinants in seven seed generations during 7 years. The results of the development of the mucosal vaccine against cervical carcinoma (carcinoma of uterine cervix evoked by human papillomaviruses of high oncogenic risks were presented in this report. We created the genetic construct consisting of 35S CaMV promoter, Ώ (omega leader of TMV, the

  18. The Human Immune Response to HIV and its Impact in the Potential Development of an Inactivated HIV Vaccine.

    Science.gov (United States)

    Rios, Adan; Pottet, Ethan C; Siwak, Edward B; Anderson, Dallas W; Yao, Qizhi C

    2016-01-01

    There is evidence that the transmission and acute phase of HIV infection triggers an immune response capable of controlling HIV subverted by the process of virus integration, essential to the replicative cycle of retroviruses. We review here two aspects that deserve consideration in light of recent developments concerning HIV transmission and vaccine development: vaccines directed against transmitted/founder viruses, and a reconsideration of inactivation as a viable means to obtain a preventive HIV vaccine. Since 80% of sexually transmitted HIV infections are caused by a single transmitted/founder variant, it is appropriate to target transmitted/founder viruses for vaccine development. Transmitted/founder virus transmission is subject to strong natural selection based on conserved signatures present in all forms of transmitted/founder HIV viruses. This provides an opportunity to pursue inactivation methods of vaccine development that allow antigenic preservation of HIV transmitted/founder viruses. The presentation to the immune system of an inactivated but antigenically preserved transmitted/founder virus should allow the development of an effective immune response against transmitted/founder viruses. This could be the base for an inactivated transmitted/founder virus HIV vaccine. We have devised a method of inactivation of HIV reverse transcriptase through the use of a novel photo-labeling procedure based on the use of photo-labeled analogs of antiretroviral compounds with specific affinity for HIV reverse transcriptase. We believe this method fulfills the required conditions for an effective preventive vaccine development: inactivation and antigenic preservation.

  19. Zika Virus: Recent Advances towards the Development of Vaccines and Therapeutics.

    Science.gov (United States)

    McArthur, Monica A

    2017-06-13

    Zika is a rapidly emerging public health threat. Although clinical infection is frequently mild, significant neurological manifestations have been demonstrated in infants born to Zika virus (ZIKV) infected mothers. Due to the substantial ramifications of intrauterine infection, effective counter-measures are urgently needed. In order to develop effective anti-ZIKV vaccines and therapeutics, improved animal models and a better understanding of immunological correlates of protection against ZIKV are required. This review will summarize what is currently known about ZIKV, the clinical manifestations and epidemiology of Zika as well as, the development of animal models to study ZIKV infection, host immune responses against ZIKV, and the current state of development of vaccines and therapeutics against ZIKV.

  20. Zika Virus: Recent Advances towards the Development of Vaccines and Therapeutics

    Science.gov (United States)

    McArthur, Monica A.

    2017-01-01

    Zika is a rapidly emerging public health threat. Although clinical infection is frequently mild, significant neurological manifestations have been demonstrated in infants born to Zika virus (ZIKV) infected mothers. Due to the substantial ramifications of intrauterine infection, effective counter-measures are urgently needed. In order to develop effective anti-ZIKV vaccines and therapeutics, improved animal models and a better understanding of immunological correlates of protection against ZIKV are required. This review will summarize what is currently known about ZIKV, the clinical manifestations and epidemiology of Zika as well as, the development of animal models to study ZIKV infection, host immune responses against ZIKV, and the current state of development of vaccines and therapeutics against ZIKV. PMID:28608813

  1. A real options approach to biotechnology Investment policy - the case of developing a Campylobacter vaccine to poultry

    DEFF Research Database (Denmark)

    Lund, Mogens; Jensen, Jørgen Dejgård

    2016-01-01

    in a cost-effective way. The development of a vaccine against Campylobacter jejuni in poultry is applied as a case study. Employing the real options methodology, the net present value of the vaccine R&D project becomes larger than a purely probabilistic expected present value throughout the different stages...... of the project – and the net present value becomes larger, when more types of real options are taken into consideration. The insight from the real options analysis reveals opportunities for new policies to promote the development of animal vaccines. One such approach might be to develop schemes combining stage...

  2. 76 FR 49776 - The Development and Evaluation of Next-Generation Smallpox Vaccines; Public Workshop

    Science.gov (United States)

    2011-08-11

    ... due to a threat of an attack with the smallpox virus. Currently, the next-generation smallpox vaccines...-generation smallpox vaccine, ACAM2000. This vaccine is based on a single plaque-purified vaccinia virus...

  3. Discovery of dormancy associated antigens of Mycobacterium tuberculosis : novel targets for the development of post-exposure or therapeutic tuberculosis vaccines

    NARCIS (Netherlands)

    Lin, May Young

    2009-01-01

    The growing number of tuberculosis (TB) casualties urges development of not only more effective drugs and preventive vaccines but also development of post-exposure/therapeutic TB vaccines. Post-exposure/therapeutic TB vaccines are needed since 2 billion people worldwide harbor a latent Mycobacterium

  4. Report from the World Health Organization's third Product Development for Vaccines Advisory Committee (PDVAC) meeting, Geneva, 8-10th June 2016.

    Science.gov (United States)

    Giersing, Birgitte K; Vekemans, Johan; Nava, Samantha; Kaslow, David C; Moorthy, Vasee

    2017-03-02

    The third meeting of WHO's Product Development for Vaccines Advisory Committee (PDVAC) was held in June 2016, with a remit to revisit the pathogen areas for which significant progress has occurred since recommendations from the 2015 meeting, as well as to consider new advances in the development of vaccines against other pathogens. Since the previous meeting, significant progress has been made with regulatory approvals of the first malaria and dengue vaccines, and the first phase III trials of a respiratory syncytial virus (RSV) vaccine candidate has started in the elderly and pregnant women. In addition, PDVAC has also supported vaccine development efforts against important emerging pathogens, including Middle Eastern Coronavirus (MERS CoV) and Zika virus. Trials of HIV and tuberculosis vaccine candidates are steadily progressing towards pivotal data points, and the leading norovirus vaccine candidate has entered a phase IIb efficacy study. WHO's Immunization, Vaccine and Biologicals (IVB) department is actively working in several pathogen areas on the recommendation of PDVAC, as well as continuing horizon scanning for advances in the development of vaccines that may benefit low and middle income countries (LMICs), such as the recent licensure of the enterovirus 71 (EV71) vaccine in China. Following on from discussions with WHO's Strategic Advisory Group of Experts (SAGE) on Immunization, PDVAC will also look beyond licensure and consider data needs for vaccine recommendation and implementation to reduce the delay between vaccine approval and vaccine impact. Copyright © 2017.

  5. Progress in development of immunocontraceptive vaccines for permanent non-surgical sterilization of cats and dogs.

    Science.gov (United States)

    Munks, M W

    2012-08-01

    Each year, millions of cats and dogs are euthanized worldwide. There are insufficient resources to control shelter animals in developed countries, as well as feral cat and wild dog population levels, with current surgical sterilization techniques. Thus, population control of these animals will likely depend on the development of new non-surgical methods for cat and dog sterilization. One promising area of research is the development of contraceptive vaccines, or immunocontraceptives. In this article, previous approaches aimed at developing contraceptive vaccines will be reviewed, with a focus on those most related to sterilization of cats and dogs. There are a number of steps in reproduction that have been, or could be, targeted by the immune system, and the advantages and obstacles for inducing immunity to each of these will be discussed. Our current understanding of how these vaccines cause sterility, and our current ability to dissect these mechanisms in cats and dogs, also will be discussed. © 2012 Blackwell Verlag GmbH.

  6. Future prospects for the development of cost-effective Adenovirus vaccines

    DEFF Research Database (Denmark)

    Fougeroux, Cyrielle; Holst, Peter J

    2017-01-01

    -vectored vaccine technology with a focus on adenoviral-based vaccines. Adenovirus (Ad) vaccines have proven to be efficient in military vaccinations against Ad4 and Ad7 and as highly efficient vectored vaccines against rabies. The question of how other adenovirus-based vaccines can become as efficient...... as the rabies vaccine is the underlying theme in this review. Here, we will first give an overview of the basic properties of vectored vaccines, followed by an introduction to the characteristics of adenoviral vectors and previously tested modifications of the vector backbone and expression cassettes...

  7. Using combinatorial bioinformatics methods to analyze annual perspective changes of influenza viruses and to accelerate development of effective vaccines

    Directory of Open Access Journals (Sweden)

    Yu-Jen Hu

    2015-08-01

    Full Text Available The standard World Health Organization procedure for vaccine development has provided a guideline for influenza viruses, but no systematic operational model. We recently designed a systemic analysis method to evaluate annual perspective sequence changes of influenza virus strains. We applied dnaml of PHYLIP 3.69, developed by Joseph Felsenstein of Washington University, and ClustalX2, developed by Larkin et al, for calculating, comparing, and localizing the most plausible vaccine epitopes. This study identified the changes in biological sequences and associated alignment alterations, which would ultimately affect epitope structures, as well as the plausible hidden features to search for the most conserved and effective epitopes for vaccine development. Addition our newly designed systemic analysis method to supplement the WHO guidelines could accelerate the development of urgently needed vaccines that might concurrently combat several strains of viruses within a shorter period.

  8. Current Status and Development of Vaccines and Other Biologics for Human Rabies Prevention.

    Science.gov (United States)

    Rupprecht, Charles E; Nagarajan, Thirumeni; Ertl, Hildegund

    2016-06-01

    Rabies is a neglected viral zoonosis with the highest case fatality of any infectious disease. Pasteur's historical accomplishments during the late 19(th) century began the process of human vaccine development, continuing to evolve into the 21(st) century. Over the past 35 years, great improvements occurred in the production of potent tissue culture vaccines and the gradual removal from the market of unsafe nerve tissue products. Timely and appropriate administration of modern biologics virtually assures survivorship, even after severe exposures. Nevertheless, in the developing world, if not provided for free nationally, the cost of a single course of human prophylaxis exceeds the average monthly wage of the common worker. Beyond traditional approaches, recombinant, sub-unit and other novel methods are underway to improve the availability of safe, effective and more affordable rabies biologics.

  9. The imperative to develop a human vaccine for the Hendra virus in Australia.

    Science.gov (United States)

    Zahoor, Bilal A; Mudie, Lucy I

    2015-01-01

    The Hendra virus (HeV) poses a significant challenge to public health in Australia. Expanding migratory patterns observed among bats and the mutation of the virus to seek and successfully infect new hosts is a significant departure from the generalized epidemiological trend. The recent discovery of equine-related infections and deaths in addition to a canine infection demonstrates the inadequacy of the current equine vaccine developed in 2012. Traditional models for controlling the spread of the vector are futile given the rapid pace at which bats' habitats are eroded. Recent ongoing zoonotic epidemics, for example, Ebola and Middle East respiratory syndrome coronavirus, demonstrate that human-to-human transmission is a distinct reality rather than an obscure possibility. The development of a human HeV vaccine is essential for the biosecurity of Australia, as part of a multipronged strategy to control HeV in Australia.

  10. The imperative to develop a human vaccine for the Hendra virus in Australia

    Directory of Open Access Journals (Sweden)

    Bilal A. Zahoor

    2015-10-01

    Full Text Available The Hendra virus (HeV poses a significant challenge to public health in Australia. Expanding migratory patterns observed among bats and the mutation of the virus to seek and successfully infect new hosts is a significant departure from the generalized epidemiological trend. The recent discovery of equine-related infections and deaths in addition to a canine infection demonstrates the inadequacy of the current equine vaccine developed in 2012. Traditional models for controlling the spread of the vector are futile given the rapid pace at which bats' habitats are eroded. Recent ongoing zoonotic epidemics, for example, Ebola and Middle East respiratory syndrome coronavirus, demonstrate that human-to-human transmission is a distinct reality rather than an obscure possibility. The development of a human HeV vaccine is essential for the biosecurity of Australia, as part of a multipronged strategy to control HeV in Australia.

  11. Strategies Using Bio-Layer Interferometry Biosensor Technology for Vaccine Research and Development

    Directory of Open Access Journals (Sweden)

    Rejane L. Petersen

    2017-10-01

    Full Text Available Bio-layer interferometry (BLI real-time, label-free technology has greatly contributed to advances in vaccine research and development. BLI Octet platforms offer high-throughput, ease of use, reliability, and high precision analysis when compared with common labeling techniques. Many different strategies have been used to immobilize the pathogen or host molecules on BLI biosensors for real-time kinetics and affinity analysis, quantification, or high-throughput titer. These strategies can be used in multiple applications and shed light onto the structural and functional aspects molecules play during pathogen-host interactions. They also provide crucial information on how to achieve protection. This review summarizes some key BLI strategies used in human vaccine research and development.

  12. Malaria in pregnancy: the relevance of animal models for vaccine development.

    Science.gov (United States)

    Doritchamou, Justin; Teo, Andrew; Fried, Michal; Duffy, Patrick E

    2017-10-06

    Malaria during pregnancy due to Plasmodium falciparum or P. vivax is a major public health problem in endemic areas, with P. falciparum causing the greatest burden of disease. Increasing resistance of parasites and mosquitoes to existing tools, such as preventive antimalarial treatments and insecticide-treated bed nets respectively, is eroding the partial protection that they offer to pregnant women. Thus, development of effective vaccines against malaria during pregnancy is an urgent priority. Relevant animal models that recapitulate key features of the pathophysiology and immunology of malaria in pregnant women could be used to accelerate vaccine development. This review summarizes available rodent and nonhuman primate models of malaria in pregnancy, and discusses their suitability for studies of biologics intended to prevent or treat malaria in this vulnerable population.

  13. Update on the Clinical Development of Candidate Malaria Vaccines

    National Research Council Canada - National Science Library

    Ballou, W. R; Arevalo-Herrera, Myriam; Carucci, Daniel; Richie, Thomas L; Corradin, Giampietro; Diggs, Carter; Druilhe, Pierre; Giersing, Birgitte K; Saul, Allan; Heppner, D. G

    2004-01-01

    The recent availability of significantly increased levels of funding for unmet medical needs in the developing world, made available by newly created public-private partnerships, has proven to be a...

  14. How can plant genetic engineering contribute to cost-effective fish vaccine development for promoting sustainable aquaculture?

    Science.gov (United States)

    Clarke, Jihong Liu; Waheed, Mohammad Tahir; Lössl, Andreas G; Martinussen, Inger; Daniell, Henry

    2013-09-01

    Aquaculture, the fastest growing food-producing sector, now accounts for nearly 50 % of the world's food fish (FAO in The state of world fisheries and aquaculture. FAO, Rome, 2010). The global aquaculture production of food fish reached 62.7 million tonnes in 2011 and is continuously increasing with an estimated production of food fish of 66.5 million tonnes in 2012 (a 9.4 % increase in 1 year, FAO, www.fao.org/fishery/topic/16140 ). Aquaculture is not only important for sustainable protein-based food fish production but also for the aquaculture industry and economy worldwide. Disease prevention is the key issue to maintain a sustainable development of aquaculture. Widespread use of antibiotics in aquaculture has led to the development of antibiotic-resistant bacteria and the accumulation of antibiotics in the environment, resulting in water and soil pollution. Thus, vaccination is the most effective and environmentally-friendly approach to combat diseases in aquaculture to manage fish health. Furthermore, when compared to >760 vaccines against human diseases, there are only about 30 fish vaccines commercially available, suggesting the urgent need for development and cost-effective production of fish vaccines for managing fish health, especially in the fast growing fish farming in Asia where profit is minimal and therefore given high priority. Plant genetic engineering has made significant contributions to production of biotech crops for food, feed, valuable recombinant proteins etc. in the past three decades. The use of plants for vaccine production offers several advantages such as low cost, safety and easy scaling up. To date a large number of plant-derived vaccines, antibodies and therapeutic proteins have been produced for human health, of which a few have been made commercially available. However, the development of animal vaccines in plants, especially fish vaccines by genetic engineering, has not yet been addressed. Therefore, there is a need to exploit

  15. Antibody Recognition of the Dengue Virus Proteome and Implications for Development of Vaccines

    Science.gov (United States)

    2011-04-01

    was replaced hy TVP360), grown in Vero cells , purified, and inactivated with formalin. Study groups, each consisting of four rhesus macaques, were...of dengue virus, each appearing t’Yclically in the tropics and subtropics along the equator . Although vaccines are currently under development, none...isolates of DENV in cultured cells , resulting in viruses that are sufficiently immu- nogenic but reduced in reactogenicity ( 10, 37). Alternatively

  16. The multi-epitope polypeptide approach in HIV-1 vaccine development.

    Science.gov (United States)

    Cano, C A

    1999-11-01

    The application of a preventive HIV vaccine is the only hope for most developing countries to halt the AIDS pandemic. A project aimed to develop a preventive AIDS vaccine is being carried out since 1992 by three Cuban research institutions: Centro de Ingeniería Genética y Biotecnologia de La Habana, Instituto de Medicina Tropical 'Pedro Kouri' and Laboratorio de Investigaciones de SIDA de La Habana. The project includes two main strategies: (a) generation of recombinant multi-epitope polypeptides (MEPs) bearing several copies of the V3 loop from different HIV-1 isolates; and (b) development of immunogens capable of inducing a cytotoxic T cell response (CTL) specific for human immunodeficiency virus type 1 (HIV-1) antigens. This article summarizes the work in the first of these strategies. Based on the sequence of the V3 loop of HIV-1 we constructed a series of MEPs and evaluated their immunogenicity in mice, rabbits and macaques. The MEP TAB9, containing six V3 epitopes from isolates LR10, JY1, RF, MN, BRVA and IIIB, was selected together with the oil adjuvant Montanide ISA720 (SEPPIC, France) to perform a Phase I clinical trial in HIV seronegative Cuban volunteers. The trial was double blinded, randomized, and fulfilled all ethical and regulatory requirements. All TAB9 vaccinated volunteers developed a strong immune response and neutralizing antibodies were observed in the 50% of the subjects. However the second and third inoculations of the vaccine were not well tolerated because transient severe local reactions appeared in some individuals. A new formulation of TAB9 is currently in pre-clinical studies and is expected to enter clinical trials in 1999.

  17. Control of Ebola hemorrhagic fever: vaccine development and our Ebola project in Sierra Leone.

    Science.gov (United States)

    Watanabe, Tokiko; Kawaoka, Yoshihiro

    2016-01-01

    Since December 2013, West Africa has experienced the worst Ebola virus outbreak in recorded history. Of the 28,639 cases reported to the World Health Organization as of March 2016, nearly half (14,124) occurred in Sierra Leone. With a case fatality rate of approximately 40%, this outbreak has claimed the lives of 11,316 individuals. No FDA-approved vaccines or drugs are available to prevent or treat Ebola virus infection. Experimental vaccines and therapies are being developed; however, their safety and efficacy are still being evaluated. Therefore, there is an urgent need to develop control measures to prevent or limit future Ebola virus outbreaks.Previously, we developed a replication-defective Ebola virus that lacks the coding region for the essential viral transcription activator VP30 (Ebola ΔVP30 virus). Here, we evaluated the vaccine efficacy of Ebola ΔVP30 virus in a non-human primate model and describe our collaborative Ebola project in Sierra Leone.

  18. Communication Challenges During the Development and Introduction of a New Meningococcal Vaccine in Africa.

    Science.gov (United States)

    Berlier, Monique; Barry, Rodrigue; Shadid, John; Sirica, Coimbra; Brunier, Alison; Hasan, Hayatee; Bouma, Enricke

    2015-11-15

    A new group A meningococcal conjugate vaccine was developed to eliminate deadly meningitis epidemics in sub-Saharan Africa. From the outset of the project, advocacy and communication strategies were developed and adjusted as the project evolved in Europe, Africa, India, and the United States. Communications efforts were evidence-based, and involved partnerships with the media and various stakeholders including African ministries of health, the World Health Organization, UNICEF, Gavi, the Centers for Disease Control and Prevention, and Médecins Sans Frontières. The implementation of an integrated communication strategy ensured the active cooperation of stakeholders while providing an organized and defined format for the dissemination of project-related developmental activities and the successful introduction of the vaccine. Early in the project, a communications strategy that engaged stakeholders and potential supporters was developed. The strategy was implemented and adapted as the project matured. Linked communication proved to be key to the successful wide-scale introduction of the PsA-TT (MenAfriVac) vaccine in Africa. © 2015 World Health Organization; licensee Oxford Journals.

  19. Approaches toward the development of DNA vaccine for influenza ...

    African Journals Online (AJOL)

    Administrator

    2011-06-13

    Jun 13, 2011 ... pathogen's genetic code (Kim and Jacob, 2009; Donnelly et al., 2005). The aims of this study were to develop eight. DNA constructs of influenza A virus in mammalian expression system, immunization of chicken by mixing the NP construct with other viral gene constructs, and evaluation study for the most ...

  20. Cost and effectiveness evaluation of prophylactic HPV vaccine in developing countries.

    Science.gov (United States)

    Termrungruanglert, Wichai; Havanond, Piyalamporn; Khemapech, Nipon; Lertmaharit, Somrat; Pongpanich, Sathirakorn; Khorprasert, Chonlakiet; Taneepanichskul, Surasak

    2012-01-01

    Approximately 80% of cervical cancer cases occur in developing countries. In Thailand, cervical cancer has been the leading cancer in females, with an incidence of 24.7 cases per 100,000 individuals per year. We constructed a decision model to simulate the lifetime economic impact for women in the context of human papillomavirus (HPV) infection prevention. HPV-related diseases were of interest: cervical cancer, cervical intraepithelial neoplasia, and genital warts. The two strategies used were 1) current practice and 2) prophylactic quadrivalent vaccine against HPV types 6, 11, 16, and 18. We developed a Markov simulation model to evaluate the incremental cost-effectiveness ratio of prophylactic HPV vaccine. Women transition through a model either healthy or developing HPV or its related diseases, or die from cervical cancer or from other causes according to transitional probabilities under the Thai health-care context. Costs from a provider perspective were obtained from King Chulalongkorn Memorial Hospital. Costs and benefits were discounted at 3% annually. Compared with no prophylactic HPV vaccine, the incremental cost-effectiveness ratio was 160,649.50 baht per quality-adjusted life-year. The mortality rate was reduced by 54.8%. The incidence of cervical cancer, cervical intraepithelial neoplasia grade 1, cervical intraepithelial neoplasia grade 2/3, and genital warts was reduced by up to 55.1%. Compared with commonly accepted standard thresholds recommended by the World Health Organization Commission on Macroeconomics and Health, the nationwide coverage of HPV vaccination in girls is likely to be cost-effective in Thailand. Copyright © 2012 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

  1. Advanced Development of the rF1V and rBV A/B Vaccines: Progress and Challenges

    OpenAIRE

    Mary Kate Hart; George A. Saviolakis; Welkos, Susan L.; House, Robert V.

    2012-01-01

    The development of vaccines for microorganisms and bacterial toxins with the potential to be used as biowarfare and bioterrorism agents is an important component of the US biodefense program. DVC is developing two vaccines, one against inhalational exposure to botulinum neurotoxins A1 and B1 and a second for Yersinia pestis, with the ultimate goal of licensure by the FDA under the Animal Rule. Progress has been made in all technical areas, including manufacturing, nonclinical, and clinical de...

  2. Policy development process for introducing new malaria interventions in Tanzania : the case of Malaria vaccine RTS,S

    OpenAIRE

    Romore, Idda

    2015-01-01

    This thesis describes research into anticipated policy processes and develops a comprehensive framework for informing policy decisions about the RTS,S malaria vaccine in Tanzania. RTS,S is the most advanced of malaria vaccines in development and has shown to protect children 5-17 months when used in conjunction with other malaria control strategies such as insecticides treated nets (ITNs) and anti-malaria drugs. The goal of this study was to analyse the decision making and policy developm...

  3. Mucin-type O-glycosylation and its potential use in drug and vaccine development

    DEFF Research Database (Denmark)

    Tarp, Mads Agervig; Clausen, Henrik

    2007-01-01

    Mucin-type O-glycans are found on mucins as well as many other glycoproteins. The initiation step in synthesis is catalyzed by a large family of polypeptide GalNAc-transferases attaching the first carbohydrate residue, GalNAc, to selected serine and threonine residues in proteins. During the last...... to recombinant therapeutics to specific acceptor sites directed by GalNAc-transferases. GalNAc-transferases have also been used to control density of glycosylation in the development of glycopeptide-based cancer vaccines. The membrane-associated mucin-1 (MUC1) has long been considered a target...... for immunotherapeutic and immunodiagnostic measures, since it is highly overexpressed and aberrantly O-glycosylated in most adenocarcinomas, including breast, ovarian, and pancreatic cancers. By using vaccines mimicking the glycosylation pattern of cancer-cells, it is possible to overcome tolerance in transgenic...

  4. Skin-resident antigen-presenting cells: Instruction manual for vaccine development

    Directory of Open Access Journals (Sweden)

    Cynthia M. Fehres

    2013-06-01

    Full Text Available The induction of antigen-specific effector T cells is driven by proper antigen presentation and co-stimulation by dendritic cells (DCs. For this reason strategies have been developed to instruct DCs for the induction of CD4+ and CD8+ T cell responses. Since DCs are localized, amongst other locations, in peripheral tissues such as the skin, new vaccines are aiming at targeting antigens to DCs in situ. Optimal skin-DC targeting in combination with adequate adjuvant delivery facilitates DC maturation and migration to draining lymph nodes and enhances antigen cross-presentation and T cell priming. In this review we describe what DC subsets populate the human skin, as well as current vaccination strategies based on targeting strategies and alternative administration for the induction of robust long-lived anti-cancer effector T cells.

  5. Structural, antigenic and immunogenic features of respiratory syncytial virus glycoproteins relevant for vaccine development

    Science.gov (United States)

    Melero, José A.; Mas, Vicente; McLellan, Jason S.

    2016-01-01

    Extraordinary progress in the structure and immunobiology of the human respiratory syncytial virus glycoproteins has been accomplished during the last few years. Determination of the fusion (F) glycoprotein structure folded in either the prefusion or the postfusion conformation was an inspiring breakthrough not only to understand the structural changes associated with the membrane fusion process but additionally to appreciate the antigenic intricacies of the F molecule. Furthermore, these developments have opened new avenues for structure-based designs of promising hRSV vaccine candidates. Finally, recent advances in our knowledge of the attachment (G) glycoprotein and its interaction with cell-surface receptors have revitalized interest in this molecule as a vaccine, as well as its role in hRSV immunobiology. PMID:27692522

  6. Progress and future opportunities in the development of vaccines against atherosclerosis.

    Science.gov (United States)

    Govea-Alonso, Dania O; Beltrán-López, Josué; Salazar-González, Jorge A; Vargas-Morales, Juan; Rosales-Mendoza, Sergio

    2017-04-01

    Atherosclerosis represents a serious global health problem that demands new therapeutic and prophylactic interventions. Considering that atherosclerosis has autoimmune and inflammatory components, immunotherapy is a possible focus to treat this disease. Areas covered: Based on the analysis of the current biomedical literature, this review describes the status on the development of vaccines against atherosclerosis. Several targets have been identified including sequences of apolipoprotein B100 (ApoB100), cholesteryl ester transfer protein (CETP), heat shock proteins (HSP), extracellular matrix proteins, T cell receptor β chain variable region 31 (TRBV31), the major outer membrane protein (MOMP), and the outer membrane protein 5 (Pomp5) from Chlamydia pneumoniae. Humoral and cellular immunities to these targets have been associated with therapeutic effects in murine models and humans. The evaluation of some candidates in clinical trials is ongoing. Expert commentary: New research paths based on the use of next generation vaccine production platforms are envisioned.

  7. African Trypanosomes Undermine Humoral Responses and Vaccine Development: Link with Inflammatory Responses?

    Directory of Open Access Journals (Sweden)

    Benoit Stijlemans

    2017-05-01

    Full Text Available African trypanosomosis is a debilitating disease of great medical and socioeconomical importance. It is caused by strictly extracellular protozoan parasites capable of infecting all vertebrate classes including human, livestock, and game animals. To survive within their mammalian host, trypanosomes have evolved efficient immune escape mechanisms and manipulate the entire host immune response, including the humoral response. This report provides an overview of how trypanosomes initially trigger and subsequently undermine the development of an effective host antibody response. Indeed, results available to date obtained in both natural and experimental infection models show that trypanosomes impair homeostatic B-cell lymphopoiesis, B-cell maturation and survival and B-cell memory development. Data on B-cell dysfunctioning in correlation with parasite virulence and trypanosome-mediated inflammation will be discussed, as well as the impact of trypanosomosis on heterologous vaccine efficacy and diagnosis. Therefore, new strategies aiming at enhancing vaccination efficacy could benefit from a combination of (i early parasite diagnosis, (ii anti-trypanosome (drugs treatment, and (iii anti-inflammatory treatment that collectively might allow B-cell recovery and improve vaccination.

  8. Challenges to the development of vaccines to hepatitis C virus that elicit neutralizing antibodies.

    Directory of Open Access Journals (Sweden)

    Heidi Edelgard Drummer

    2014-07-01

    Full Text Available Despite 20 years of research, a vaccine to prevent hepatitis C virus (HCV infection has not been developed. A vaccine to prevent HCV will need to induce broadly reactive immunity able to prevent infection by the 7 genetically and antigenically distinct genotypes circulating world-wide. Hepatitis C virus encodes two surface exposed glycoproteins, E1 and E2 that function as a heterodimer to mediate viral entry. Neutralizing antibodies (NAbs to both E1 and E2 have been described with the major NAb target being E2. The function of E2 is to attach virions to host cells via cell surface receptors that include, but is not limited to, the tetraspanin CD81 and scavenger receptor B class I. However, E2 has developed a number of immune evasion strategies to limit the effectiveness of the NAb response and possibly limit the ability of the immune system to generate potent NAbs in natural infection. Hypervariable regions that shield the underlying core domain, subdominant neutralization epitopes and glycan shielding combine to make E2 a difficult target for the immune system. This review summarizes recent information on the role of neutralizing antibodies to prevent HCV infection, the targets of the neutralizing antibody response and structural information on gly