Tocotrienols are good adjuvants for developing cancer vaccines

International Nuclear Information System (INIS)

Abdul Hafid, Sitti Rahma; Radhakrishnan, Ammu Kutty; Nesaretnam, Kalanithi

2010-01-01

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. 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. 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. Our study show that TRF has the potential to be an adjuvant to augment DC based immunotherapy

Rhabdoviruses as vaccine platforms for infectious disease and cancer.

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Zemp, Franz; Rajwani, Jahanara; Mahoney, Douglas J

2018-05-21

The family Rhabdoviridae (RV) comprises a large, genetically diverse collection of single-stranded, negative sense RNA viruses from the order Mononegavirales. Several RV members are being developed as live-attenuated vaccine vectors for the prevention or treatment of infectious disease and cancer. These include the prototype recombinant Vesicular Stomatitis Virus (rVSV) and the more recently developed recombinant Maraba Virus, both species within the genus Vesiculoviridae. A relatively strong safety profile in humans, robust immunogenicity and genetic malleability are key features that make the RV family attractive vaccine platforms. Currently, the rVSV vector is in preclinical development for vaccination against numerous high-priority infectious diseases, with clinical evaluation underway for HIV/AIDS and Ebola virus disease. Indeed, the success of the rVSV-ZEBOV vaccine during the 2014-15 Ebola virus outbreak in West Africa highlights the therapeutic potential of rVSV as a vaccine vector for acute, life-threatening viral illnesses. The rVSV and rMaraba platforms are also being tested as 'oncolytic' cancer vaccines in a series of phase 1-2 clinical trials, after being proven effective at eliciting immune-mediated tumour regression in preclinical mouse models. In this review, we discuss the biological and genetic features that make RVs attractive vaccine platforms and the development and ongoing testing of rVSV and rMaraba strains as vaccine vectors for infectious disease and cancer.

Human Papilloma Virus Vaccine: Future of Cervical Cancer Prevention

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Jannatul Fardows

2016-09-01

Full Text Available Cervical cancer is a deadly cancer that clutches lives of the women in most of the cases due to lack of consciousness about the disease in the developing countries. It remains a threat which is second only to breast cancer in overall disease burden for women throughout the world. Cervical cancer is almost a preventable disease by prophylactic vaccine and routine screening. Both Cervarix and Gardasil vaccines have been effective in preventing persistent infection with targeted HPV types and in preventing cervical intraepithelial lesions. It is safe and nearly 100% effective if given before onset of sexual activity. This review article is aimed to explore different aspects of this vaccine as well as to develop awareness among health professionals of different disciplines.

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.

Preventing Cervical Cancer with HPV Vaccines

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Cervical cancer can be prevented with HPV vaccines. NCI-supported researchers helped establish HPV as a cause of cervical cancer. They also helped create the first HPV vaccines, were involved in the vaccine trials, and contribute to ongoing studies.

RNA-Based Vaccines in Cancer Immunotherapy

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Megan A. McNamara

2015-01-01

Full Text Available RNA vaccines traditionally consist of messenger RNA synthesized by in vitro transcription using a bacteriophage RNA polymerase and template DNA that encodes the antigen(s of interest. Once administered and internalized by host cells, the mRNA transcripts are translated directly in the cytoplasm and then the resulting antigens are presented to antigen presenting cells to stimulate an immune response. Alternatively, dendritic cells can be loaded with either tumor associated antigen mRNA or total tumor RNA and delivered to the host to elicit a specific immune response. In this review, we will explain why RNA vaccines represent an attractive platform for cancer immunotherapy, discuss modifications to RNA structure that have been developed to optimize mRNA vaccine stability and translational efficiency, and describe strategies for nonviral delivery of mRNA vaccines, highlighting key preclinical and clinical data related to cancer immunotherapy.

The pig as a model for therapeutic human anti-cancer vaccine development, elucidating the T-cell reactivity against IDO and RhoC

DEFF Research Database (Denmark)

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

is important. Previous development of therapeutic cancer vaccines has largely been based on studies in mice and the majority of these candidate vaccines failed to establish therapeutic responses in subsequent human clinical trials. Since the porcine immunome is more closely related to the human counterpart, we...... here introduce pigs as a superior large animal model for human cancer vaccine development via the use of our unique technology for swine leukocyte antigen (SLA) production. IDO and RhoC, both known to be important in human cancer development and progression, were used as vaccine targets. Pigs were......, and peptide-SLA complex stability measurements revealed 89 stable (t½ ≥ 0.5 hour) complexes. Vaccine-induced peptide-specific CTL responses were monitored using IFN-γ release as a read out. We found responses to IDO- and RhoC-derived peptides across all groups; surprisingly non-stably binding peptides also...

Synthetic Self-Adjuvanting Glycopeptide Cancer Vaccines

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Payne, Richard; McDonald, David; Byrne, Scott

2015-10-01

Due to changes in glycosyltransferase expression during tumorigenesis, the glycoproteins of cancer cells often carry highly truncated carbohydrate chains compared to those on healthy cells. These glycans are known as tumor-associated carbohydrate antigens, and are prime targets for use in vaccines for the prevention and treatment of cancer. Herein, we review the state-of-the-art in targeting the immune system towards tumor-associated glycopeptide antigens via synthetic self adjuvanting vaccines, in which the antigenic and adjuvanting moieties of the vaccines are present in the same molecule. The majority of the self-adjuvanting glycopeptide cancer vaccines reported to date employ antigens from mucin 1, a protein which is highly over-expressed and aberrantly glycosylated in many forms of cancer. The adjuvants used in these vaccines predominantly include lipopeptide- or lipoamino acid-based TLR2 agonists, although studies investigating stimulation of TLR9 and TLR4 are also discussed. Most of these adjuvants are highly lipophilic, and, upon conjugation to antigenic peptides, provide amphiphilic vaccine molecules. The amphiphilic nature of these vaccine constructs can lead to the formation of higher-order structures by vaccines in solution, which are likely to be important for their efficacy in vivo.

Polyclonal immune responses to antigens associated with cancer signaling pathways and new strategies to enhance cancer vaccines.

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Clay, Timothy M; Osada, Takuya; Hartman, Zachary C; Hobeika, Amy; Devi, Gayathri; Morse, Michael A; Lyerly, H Kim

2011-04-01

Aberrant signaling pathways are a hallmark of cancer. A variety of strategies for inhibiting signaling pathways have been developed, but monoclonal antibodies against receptor tyrosine kinases have been among the most successful. A challenge for these therapies is therapeutic unresponsiveness and acquired resistance due to mutations in the receptors, upregulation of alternate growth and survival pathways, or inadequate function of the monoclonal antibodies. Vaccines are able to induce polyclonal responses that can have a multitude of affects against the target molecule. We began to explore therapeutic vaccine development to antigens associated with these signaling pathways. We provide an illustrative example in developing therapeutic cancer vaccines inducing polyclonal adaptive immune responses targeting the ErbB family member HER2. Further, we will discuss new strategies to augment the clinical efficacy of cancer vaccines by enhancing vaccine immunogenicity and reversing the immunosuppressive tumor microenvironment.

Sex, drugs, and politics: the HPV vaccine for cervical cancer.

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Casper, Monica J; Carpenter, Laura M

2008-09-01

HPV is the most common sexually transmitted infection in the world. While most strains are relatively harmless, some increase a woman's risk of developing cervical cancer. This article explores the intimate, contested relationships among etiologies of cervical cancer, development and use of the new HPV vaccine, and contested notions of sexuality. We particularly focus on shifts in US health care and sexual politics, where the vaccine has animated longstanding concerns about vaccination (e.g. parental rights, cost, specialisation) and young women's bodies and behaviour. We conclude that vaccines are a distinctive kind of pharmaceutical, invoking notions of contagion and containment, and that politics shape every aspect of the pharmaceutical life course.

Human Papillomavirus and Vaccination in Cervical Cancer

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Kung-Liahng Wang

2007-12-01

Full Text Available Cervical cancer is not only the most frequently reported cancer among women, but also the most common female genital tract neoplasm in Taiwan. Early detection is effective, because the development, maintenance and progression of precursor lesions (cervical intraepithelial neoplasia [CIN] evolve slowly into invasive cancer, typically over a period of more than 10 years. It is now recognized that human papillomavirus (HPV infection is a necessary cause for over 99% of cervical cancer cases. Advances in the understanding of the causative role of HPV in the etiology of high-grade cervical lesions (CIN 2/3 and cervical cancer have led to the development, evaluation and recommendation of HPV-based technologies for cervical cancer prevention and control. The prevention of HPV infection before the onset of CIN is now possible with recently available prophylactic HPV vaccines, e.g. the quadrivalent Gardasil (Merck & Co., NJ, USA and bivalent Cervarix (GlaxoSmithKline, London, UK. This review article provides an up-to-date summary of recent studies and available information concerning HPV and vaccination in cervical cancer.

Quadrivalent human papillomavirus recombinant vaccine: The first vaccine for cervical cancers

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Sharma Rashmi

2007-01-01

Full Text Available Gardasil ® is the first quadrivalent human papillomavirus (HPV- types 6, 11, 16, 18 recombinant vaccine approved by the FDA on June 8, 2006. It induces genotype-specific virus-neutralizing antibodies and prevents infection with HPV. Various clinical trials demonstrated a reduction in the incidence of vaccine-type-specific persistent infections and of associated moderate- and high-grade cervical dysplasias and carcinomas in situ after its use. Gardasil is currently approved by FDA for prevention of genital warts, cancers and precancerous conditions of cervix and vulva in 9-26 years old females. Three doses of 0.5 ml of gardasil each at 0, 2 and 6 months are given intramuscularly. It is contraindicated in individuals who are hypersensitive to the active substances or to any of the excipients of the vaccine, patients with bleeding abnormalities or patients on anticoagulant therapy and during pregnancy. However, the vaccine, at an estimated $300-500 per course, is too expensive for many women in developing countries. Moreover, question regarding the longevity of the protection by vaccine is still unsolved. Hence, longer studies are required to establish its real status in cancer prevention.

Radiation and Anti-Cancer Vaccines: A Winning Combination.

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Cadena, Alexandra; Cushman, Taylor R; Anderson, Clark; Barsoumian, Hampartsoum B; Welsh, James W; Cortez, Maria Angelica

2018-01-30

The emerging combination of radiation therapy with vaccines is a promising new treatment plan in the fight against cancer. While many cancer vaccines such as MUC1, p53 CpG oligodeoxynucleotide, and SOX2 may be great candidates for antitumor vaccination, there still remain many investigations to be done into possible vaccine combinations. One fruitful partnership that has emerged are anti-tumor vaccines in combination with radiation. Radiation therapy was previously thought to be only a tool for directly or indirectly damaging DNA and therefore causing cancer cell death. Now, with much preclinical and clinical data, radiation has taken on the role of an in situ vaccine. With both cancer vaccines and radiation at our disposal, more and more studies are looking to combining vaccine types such as toll-like receptors, viral components, dendritic-cell-based, and subunit vaccines with radiation. While the outcomes of these combinatory efforts are promising, there is still much work to be covered. This review sheds light on the current state of affairs in cancer vaccines and how radiation will bring its story into the future.

Role of HPV Vaccine in the Prevention of Cervical Cancer

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Saleh JA

2013-08-01

Full Text Available Background: Cervical cancer which affects relatively young women of child bearing age is considered to be the second most common cancer in women and a leading cause of cancer-related deaths in developing countries, a reflection of global health inequity. There are more than 450,000 newly diagnosed cases annually with over a quarter of million deaths recorded out of which over 80 percent are from the developing countries especially Africa, South Asia, South and Central America, and the Caribbean, with an exponential rise expected from this figure by 2020. The preventive measures available (Pap smear and HPV vaccine aimed at reducing morbidity and mortality associated with this disease, has been shown to be very effective but difficult to implement especially in the developing countries partly due to lack of resources and mainly lack of government commitment amongst other things. This forms the basis of this review to look at the position of HPV vaccine in the prevention of cancer of the cervix. Method: In the course of this write-up, relevant literatures were reviewed using manual library search, relevant websites and internet articles. The key words employed were: cervical cancer, human papilloma virus, pap smear and vaccination. Results: It has been shown that, where resources permits, combining HPV vaccine in combination with pap smear screening methods especially to high risk group would greatly reduce the morbidity and mortality associated with cancer of the cervix. Conclusion: Although there are so many essential questions still unanswered, considering the havoc caused by this preventable gynaecological malignancy and coupled with the ever increasing costs of its treatment, the advantages of using HPV vaccine in addition to routine Pap smear as a means of preventing cancer of the cervix greatly outweighs the disadvantages. However, there is the need for caution to be adhered to when it comes to large scale vaccination programs in view of

Anti-idiotypic antibodies as cancer vaccines: achievements and future improvements

International Nuclear Information System (INIS)

Ladjemi, Maha Z.

2012-01-01

Since the discovery of tumor-associated antigens (TAAs), researchers have tried to develop immune-based anti-cancer therapies. Thanks to their specificity, monoclonal antibodies (mAbs) offer the major advantage to induce fewer side effects than those caused by non-specific conventional treatments (e.g., chemotherapy, radiotherapy). Passive immunotherapy by means of mAbs or cytokines has proved efficacy in oncology and validated the use of immune-based agents as part of anti-cancer treatment options. The next step was to try to induce an active immune protection aiming to boost own’s host immune defense against TAAs. Cancer vaccines are thus developed to specifically induce active immune protection targeting only tumor cells while preserving normal tissues from a non-specific toxicity. But, as most of TAAs are self antigens, an immune tolerance against them exists representing a barrier to effective vaccination against these oncoproteins. One promising approach to break this immune tolerance consists in the use of anti-idiotypic (anti-Id) mAbs, so called Ab2, as antigen surrogates. This vaccination strategy allows also immunization against non-proteic antigens (such as carbohydrates). In some clinical studies, anti-Id cancer vaccines indeed induced efficient humoral and/or cellular immune responses associated with clinical benefit. This review article will focus on recent achievements of anti-Id mAbs use as cancer vaccines in solid tumors.

Human Papillomavirus Vaccine as an Anti-cancer Vaccine: Collaborative Efforts to Promote HPV Vaccine in the National Comprehensive Cancer Control Program

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Townsend, Julie S.; Steele, C. Brooke; Hayes, Nikki; Bhatt, Achal; Moore, Angela R.

2018-01-01

Background Widespread use of the HPV vaccine has the potential to reduce incidence from HPV-associated cancers. However, vaccine uptake among adolescents remains well below the Healthy People 2020 targets. The Centers for Disease Control and Prevention (CDC)’s National Comprehensive Cancer Control Program awardees (NCCCP) are well positioned to work with immunization programs to increase vaccine uptake. Methods CDC’s chronic disease management information system was queried for objectives and activities associated with HPV vaccine that were reported by NCCCP awardees from 2013 – 2016 as part of program reporting requirements. A content analysis was conducted on the query results to categorize interventions according to strategies outlined in The Guide to Community Preventive Services and the 2014 President’s Cancer Panel report. Results Sixty-two percent of NCCCP awardees had planned or implemented at least one activity since 2013 to address low HPV vaccination coverage in their jurisdictions. Most NCCCP awardees (86%) reported community education activities, while 65% reported activities associated with provider education. Systems-based strategies such as client reminders or provider assessment and feedback were each reported by less than 25% of NCCCP awardees. Conclusion Many NCCCP awardees report planning or implementing activities to address low HPV vaccination coverage, often in conjunction with state immunization programs. NCCCP awardees can play a role in increasing HPV vaccination coverage through their cancer prevention and control expertise and access to partners in the health care community. PMID:28263672

Successes and Challenges of Vaccines to Prevent HPV-associated Cancers

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Dr. John T. Schiller received his bachelor’s degree in Molecular Biology from the University of Wisconsin, Madison in 1975, and his master’s and PhD degrees in Microbiology from the University of Washington, Seattle, in 1978 and 1982, respectively. He is currently a NIH Distinguished Investigator and Section Chief in the Laboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute, Bethesda, MD. In his 35 years at the NCI, Dr. Schiller has studied various aspects of papillomavirus molecular biology, immunology, and epidemiology The laboratory headed by Dr. Schiller and Dr. Lowy led in the discovery, characterization, and clinical testing of virus-like particle (VLP) vaccines to prevent the HPV infections that cause cervical and other cancers. They have facilitated technology transfer to potential HPV vaccine manufactures in developing countries and provided leadership in promoting global public health issues related to the implementation of HPV vaccination. They have received numerous awards for this work including the 2007 Sabin Gold Medal Award, the 2014 National Medal of Technology and Innovation, and the 2017 Lasker~DeBakey Clinical Medical Research Award. Dr. Schiller’s current interests include basic studies of papillomavirus virion assembly and infection, the development of 2 generation HPV vaccines, and vaccines and therapies for other infectious diseases and cancers.  

Cancer vaccines: an update with special focus on ganglioside antigens.

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Bitton, Roberto J; Guthmann, Marcel D; Gabri, Mariano R; Carnero, Ariel J L; Alonso, Daniel F; Fainboim, Leonardo; Gomez, Daniel E

2002-01-01

Vaccine development is one of the most promising and exciting fields in cancer research; numerous approaches are being studied to developed effective cancer vaccines. The aim of this form of therapy is to teach the patient's immune system to recognize the antigens expressed in tumor cells, but not in normal tissue, to be able to destroy these abnormal cells leaving the normal cells intact. In other words, is an attempt to teach the immune system to recognize antigens that escaped the immunologic surveillance and are by it, therefore able to survive and, in time, disseminate. However each research group developing a cancer vaccine, uses a different technology, targeting different antigens, combining different carriers and adjuvants, and using different immunization schedules. Most of the vaccines are still experimental and not approved by the US or European Regulatory Agencies. In this work, we will offer an update in the knowledge in cancer immunology and all the anticancer vaccine approaches, with special emphasis in ganglioside based vaccines. It has been demonstrated that quantitative and qualitative changes occur in ganglioside expression during the oncogenic transformation. Malignant transformation appears to activate enzymes associated with ganglioside glycosylation, resulting in altered patterns of ganglioside expression in tumors. Direct evidence of the importance of gangliosides as potential targets for active immunotherapy has been suggested by the observation that human monoclonal antibodies against these glycolipids induce shrinkage of human cutaneous melanoma metastasis. Thus, the cellular over-expression and shedding of gangliosides into the interstitial space may play a central role in cell growth regulation, immune tolerance and tumor-angiogenesis, therefore representing a new target for anticancer therapy. Since 1993 researchers at the University of Buenos Aires and the University of Quilmes (Argentina), have taken part in a project carried out by

9-Valent HPV vaccine for cancers, pre-cancers and genital warts related to HPV.

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Pitisuttithum, Punnee; Velicer, Christine; Luxembourg, Alain

2015-01-01

Human papillomavirus (HPV) is the causative agent of nearly all cervical cancer cases as well as a substantial proportion of anal, vulvar, vaginal, penile and oropharyngeal cancers, making it responsible for approximately 5% of the global cancer burden. The first-generation HPV vaccines that is, quadrivalent HPV type 6/11/16/18 vaccine and bivalent HPV type 16/18 vaccine were licensed in 2006 and 2007, respectively. A second-generation 9-valent HPV type 6/11/16/18/31/33/45/52/58 vaccine with broader cancer coverage was initiated even before the first vaccines were approved. By preventing HPV infection and disease due to HPV31/33/45/52/58, the 9vHPV vaccine has the potential to increase prevention of cervical cancer from 70 to 90%. In addition, the 9vHPV vaccine has the potential to prevent 85-95% of HPV-related vulvar, vaginal and anal cancers. Overall, the 9vHPV vaccine addresses a significant unmet medical need, although further health economics and implementation research is needed.

Clinical cancer chemoprevention: From the hepatitis B virus (HBV vaccine to the human papillomavirus (HPV vaccine

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Horng-Jyh Tsai

2015-04-01

Full Text Available Approximately 2 million new cancer cases are attributed to infectious agents each year worldwide. Vaccines for the hepatitis B virus (HBV, a risk factor of hepatocellular cancer, and human papillomavirus (HPV, a risk factor of cervical cancer, are considered major successes in clinical chemoprevention of cancer. In Taiwan, the first evidence of cancer prevention through vaccinations was provided by HBV vaccination data in infants. The Taiwanese HBV vaccination program has since become a model immunization schedule for newborns worldwide. Persistent infection with high-risk HPV is generally accepted as prerequisite for cervical cancer diagnosis; however, cervical cancer is a rare complication of HPV infections. This is due to the fact that such infections tend to be transient. The safety and efficacy of both available HPV quadrivalent vaccine and bivalent vaccine are not in doubt at the present time. Until a human cytomegalovirus (CMV vaccine becomes available, simple hygienic practices, such as hand washing, can prevent CMV infection both before and during pregnancy. Each country should establish her official guidelines regarding which vaccines should be used to treat various conditions, the target population (i.e., universal or limited to a selected population, and the immunization schedules. After a vaccine is recommended, decisions regarding reimbursement by the public health care fund are evaluated. The guidelines become part of the immunization schedule, which is updated annually and published in the official bulletin. In conclusion, both HBV and HPV vaccines are considered major successes in the chemoprevention of cancer.

Can dendritic cells improve whole cancer cell vaccines based on immunogenically killed cancer cells?

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Cicchelero, Laetitia; Denies, Sofie; Devriendt, Bert; de Rooster, Hilde; Sanders, Niek N

2015-01-01

Immunogenic cell death (ICD) offers interesting opportunities in cancer cell (CC) vaccine manufacture, as it increases the immunogenicity of the dead CC. Furthermore, fusion of CCs with dendritic cells (DCs) is considered a superior method for generating whole CC vaccines. Therefore, in this work, we determined in naive mice whether immunogenically killed CCs per se (CC vaccine) elicit an antitumoral immune response different from the response observed when immunogenically killed CCs are associated with DCs through fusion (fusion vaccine) or through co-incubation (co-incubation vaccine). After tumor inoculation, the type of immune response in the prophylactically vaccinated mice differed between the groups. In more detail, fusion vaccines elicited a humoral anticancer response, whereas the co-incubation and CC vaccine mainly induced a cellular response. Despite these differences, all three approaches offered a prophylactic protection against tumor development in the murine mammary carcinoma model. In summary, it can be concluded that whole CC vaccines based on immunogenically killed CCs may not necessarily require association with DCs to elicit a protective anticancer immune response. If this finding can be endorsed in other cancer models, the manufacture of CC vaccines would greatly benefit from this new insight, as production of DC-based vaccines is laborious, time-consuming and expensive. PMID:26587315

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

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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.

Vaxjo: a web-based vaccine adjuvant database and its application for analysis of vaccine adjuvants and their uses in vaccine development.

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Sayers, Samantha; Ulysse, Guerlain; Xiang, Zuoshuang; He, Yongqun

2012-01-01

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.

Unconventional cytokine profiles and development of T cell memory in long-term survivors after cancer vaccination

DEFF Research Database (Denmark)

Kyte, Jon Amund; Trachsel, Sissel; Risberg, Bente

2009-01-01

Cancer vaccine trials frequently report on immunological responses, without any clinical benefit. This paradox may reflect the challenge of discriminating between effective and pointless immune responses and sparse knowledge on their long-term development. Here, we have analyzed T cell responses...... in long-term survivors after peptide vaccination. There were three main study aims: (1) to characterize the immune response in patients with a possible clinical benefit. (2) To analyze the long-term development of responses and effects of booster vaccination. (3) To investigate whether the Th1/Th2...... display unconventional cytotoxicity and specifically kill tumor cells expressing mutated TGFbeta receptor II. Cytokine profiling on the long-term survivors demonstrates high IFN gamma/IL10-ratios, favoring immunity over tolerance, and secretion of multiple chemokines likely to mobilize the innate...

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

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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.

Vaccination with apoptosis colorectal cancer cell pulsed autologous ...

African Journals Online (AJOL)

To investigate vaccination with apoptosis colorectal cancer (CRC) cell pulsed autologous dendritic cells (DCs) in advanced CRC, 14 patients with advanced colorectal cancer (CRC) were enrolled and treated with DCs vaccine to assess toxicity, tolerability, immune and clinical responses to the vaccine. No severe toxicity ...

Preventing cervical cancer through human papillomavirus vaccination: perspective from focus groups.

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Wong, Li Ping

2009-04-01

It has been a little more than a year ago since the prophylactic vaccine against human papillomavirus (HPV) was released in Malaysia. Little is known about parental knowledge and acceptability of the vaccine. The objective of this study is to assess the mother's knowledge and attitudes toward HPV vaccination. The results are aimed to provide insights into the provision of appropriate educational and promotional program for effective immunization uptake. Purposive sampling method was adopted for recruitment of participants. A total of 47 mothers participated across 8 focus group discussions carried out between October and November 2007. The transcribed group discussions were analyzed using open-, axial-, and selective-coding procedures. Respondents have low awareness about the newly released vaccine and the link between HPV and cervical cancer. When provided with information about HPV and cervical cancer, most mothers were in favor of protecting their daughters from cervical cancer using the vaccine. As with any new vaccine, efficacy and safety were the major concern, particularly when the vaccine is recommended to preadolescent. Many expressed concern about the high cost of the vaccine and hope that the inoculation could be at least partially subsidized by the government. A minority were concerned that the sexually transmitted disease-related vaccine would promote sexual activities, and some opposed making vaccination mandatory. For Muslim respondents, the kosher issue of HPV vaccine was an important factor for acceptance. Developing public health messages that focus on the susceptibility of HPV infection and its link to cervical cancer to educate parents may have the greatest impact on improving the uptake of the vaccine. Apart from the major concern about safety and efficacy, affordability, and acceptability of vaccinating young children, religious and ethnic backgrounds were important considerations when recommending the HPV vaccine. To foster broad acceptance

Muc1 based breast cancer vaccines: role of post translational modifications

International Nuclear Information System (INIS)

Begum, M.; Khurshid, R.; Nagra, S.A.

2008-01-01

Vaccine development is one of the most promising fields in cancer research. After autologous transplantation, due to low tumour burden, patients are more likely to respond immunologically to a cancer vaccine. MUC1 with its adhesive and anti adhesive functions, immunostimulatory and immunosuppressive activities, is therefore a good candidate for breast cancer vaccine. A structure-based insight into the immunogenicity of natural MUC1 glyco forms, of its sub-domains, motifs and post translational modification like glycosylation and myriostoylation may aid the design of tumour vaccines. Primary sequences of human MUC1 were retrieved from the SWISSPROT data bank. Protein pattern search: The primary sequence of Human MUC1 was searched at PROSITE (a dictionary of protein sites and patterns) database. Our study observes that post-translational modifications play an important role in presenting MUC1 as a candidate for breast cancer vaccine. It is found that the phosphorylation and glycosylation of important functional motifs of MUC1 may take part in the production of cytokines that may provide immunization. (author)

The Vaccine and Cervical Cancer Screen project 2 (VACCS 2 ...

African Journals Online (AJOL)

The Vaccine and Cervical Cancer Screen project 2 (VACCS 2): Linking cervical cancer screening to a two-dose HPV vaccination ... In VACCS 1 the feasibility of linking cervical cancer with HPV vaccination was demonstrated. ... Article Metrics.

Vaccines 2.0 | Center for Cancer Research

Science.gov (United States)

In 1974, Jay A. Berzofsky, M.D., Ph.D., now Chief of CCR’s Vaccine Branch, came to NIH to study protein folding. His curious mind and collaborative spirit quickly led him into the intertwined fields of immunology and vaccine development. With close to 500 publications to his name, Berzofsky has pioneered the characterization of B- and T-cell epitopes and their modification to make vaccines directed against cancer and chronic infectious diseases. He has also characterized and taken advantage of the cellular and molecular regulators of immune responses in order to enhance tumor immunity and vaccine efficacy. In the last several years, he has translated many of these strategies into promising clinical trials. From the microcosm of his laboratory, he brings the same spirit of cross-fertilizing, bench-to-bedside research to leading the Vaccine Branch as a whole.

Cost-effectiveness of adding vaccination with the AS04-adjuvanted human papillomavirus 16/18 vaccine to cervical cancer screening in Hungary

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Vokó Zoltán

2012-10-01

Full Text Available Abstract Background The cervical cancer screening program implemented in Hungary to date has not been successful. Along with screening, vaccination is an effective intervention to prevent cervical cancer. The aim of this study was to assess the cost-effectiveness of adding vaccination with the human papillomavirus 16/18 vaccine to the current cervical cancer screening program in Hungary. Methods We developed a cohort simulation state-transition Markov model to model the life course of 12-year-old girls. Eighty percent participation in the HPV vaccination program at 12 years of age was assumed. Transitional probabilities were estimated using data from the literature. Local data were used regarding screening participation rates, and the costs were estimated in US $. We applied the purchasing power parity exchange rate of 129 HUF/$ to the cost data. Only direct health care costs were considered. We used a 3.7% discount rate for both the cost and quality-adjusted life years (QALYs. The time horizon was 88 years. Results Inclusion of HPV vaccination at age 12 in the cervical cancer prevention program was predicted to be cost-effective. The incremental cost-effectiveness ratio (ICER of adding HPV vaccination to the current national cancer screening program was estimated to be 27 588 $/QALY. The results were sensitive to the price of the vaccine, the discount rate, the screening participation rate and whether herd immunity was taken into account. Conclusions Our modeling analysis showed that the vaccination of 12-year-old adolescent girls against cervical cancer with the AS04-adjuvanted human papillomavirus 16/18 vaccine would be a cost-effective strategy to prevent cervical cancer in Hungary.

Progress towards development of an HIV vaccine: report of the AIDS Vaccine 2009 Conference.

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Ross, Anna Laura; Bråve, Andreas; Scarlatti, Gabriella; Manrique, Amapola; Buonaguro, Luigi

2010-05-01

The search for an HIV/AIDS vaccine is steadily moving ahead, generating and validating new concepts in terms of novel vectors for antigen delivery and presentation, new vaccine and adjuvant strategies, alternative approaches to design HIV-1 antigens for eliciting protective cross-neutralising antibodies, and identification of key mechanisms in HIV infection and modulation of the immune system. All these different perspectives are contributing to the unprecedented challenge of developing a protective HIV-1 vaccine. The high scientific value of this massive effort is its great impact on vaccinology as a whole, providing invaluable scientific information for the current and future development of new preventive vaccine as well as therapeutic knowledge-based infectious-disease and cancer vaccines. Copyright 2010 Elsevier Ltd. All rights reserved.

HPV Prevalence in Colombian Women with Cervical Cancer: Implications for Vaccination in a Developing Country

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Raúl Murillo

2009-01-01

Full Text Available Human Papillomavirus (HPV vaccines have been considered potentially cost-effective for the reduction of cervical cancer burden in developing countries; their effectiveness in a public health setting continues to be researched. We conducted an HPV prevalence survey among Colombian women with invasive cancer. Paraffin-embedded biopsies were obtained from one high-risk and one low-middle-risk regions. GP5+/GP6+ L1 primers, RLB assays, and E7 type specific PCR were used for HPV-DNA detection. 217 cases were analyzed with 97.7% HPV detection rate. HPV-16/18 prevalence was 63.1%; HPV-18 had lower occurrence in the high-risk population (13.8% versus 9.6% allowing for the participation of less common HPV types; HPV-45 was present mainly in women under 50 and age-specific HPV type prevalence revealed significant differences. Multiple high-risk infections appeared in 16.6% of cases and represent a chance of replacement. Age-specific HPV prevalence and multiple high-risk infections might influence vaccine impact. Both factors highlight the role of HPVs other than 16/18, which should be considered in cost-effectiveness analyses for potential vaccine impact.

Cancer vaccines: looking to the future. Interview by Jenaid Rees.

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Apostolopoulos, Vasso

2013-10-01

Interview by Jenaid Rees (Commissioning Editor) Vasso Apostolopoulos has been working in the field of cancer vaccines since 1991, and human clinical trials on her work have been conducted since 1994. Her work has been at the forefront of scientific research into the development of a vaccine for cancer and she has received over 90 awards and honours in recognition of her achievements. Some notable awards include, the Premier's Award for medical research, was named Young Australian of the Year (Victoria), recipient of the Channel 10/Herald Sun Young Achiever of the Year Award as well as being awarded the Order of Brigadier General of the Phoenix Battalion by the Greek President. In 1998 Apostolopoulos received the NHMRC CJ Martin Research Fellowship and worked at the Scripps Research Institute in California, USA, for 3.5 years and returned to the Austin Research Institute (VIC, Australia), and headed the Immunology and Vaccine Laboratory receiving the NHMRC RD Wright Fellowship. Upon her return to Australia, Apostolopoulos received the Victorian Tall Poppy Award, the Bodossaki Foundation Academic Prize, was inducted into the Victorian Honour roll of Women, was a torchbearer for the Melbourne leg of the International Athens 2004 Olympic Torch Relay, was named Woman of the Year, and is an Australia Day Ambassador. Her contribution into cancer research, vaccines and immunology has been extensive - publishing over 200 scientific papers and books, an inventor on 14 patents and collaborates with over 50 national and international Research Institutes and Universities. Her current research interests are in the development of new improved cancer vaccines and new modes of antigen delivery for immune stimulation. She is also interested in chronic diseases treatment and prevention through immunotherapy. She serves on the Editorial Board for Expert Review of Vaccines.

A cost-utility analysis of cervical cancer vaccination in preadolescent Canadian females

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Merid Maraki

2009-10-01

Full Text Available Abstract Background Despite the fact that approximately 70% of Canadian women undergo cervical cancer screening at least once every 3 years, approximately 1,300 women were diagnosed with cervical cancer and approximately 380 died from it in 2008. This study estimates the effectiveness and cost-effectiveness of vaccinating 12-year old Canadian females with an AS04-adjuvanted cervical cancer vaccine. The indirect effect of vaccination, via herd immunity, is also estimated. Methods A 12-health-state 1-year-cycle Markov model was developed to estimate lifetime HPV related events for a cohort of 12-year old females. Annual transition probabilities between health-states were derived from published literature and Canadian population statistics. The model was calibrated using Canadian cancer statistics. From a healthcare perspective, the cost-effectiveness of introducing a vaccine with efficacy against HPV-16/18 and evidence of cross-protection against other oncogenic HPV types was evaluated in a population undergoing current screening practices. The base-case analysis included 70% screening coverage, 75% vaccination coverage, $135/dose for vaccine, and 3% discount rate on future costs and health effects. Conservative herd immunity effects were taken into account by estimated HPV incidence using a mathematical model parameterized by reported age-stratified sexual mixing data. Sensitivity analyses were performed to address parameter uncertainties. Results Vaccinating 12-year old females (n = 100,000 was estimated to prevent between 390-633 undiscounted cervical cancer cases (reduction of 47%-77% and 168-275 undiscounted deaths (48%-78% over their lifetime, depending on whether or not herd immunity and cross-protection against other oncogenic HPV types were included. Vaccination was estimated to cost $18,672-$31,687 per QALY-gained, the lower range representing inclusion of cross-protective efficacy and herd immunity. The cost per QALY-gained was most

Cancer testis antigen vaccination affords long-term protection in a murine model of ovarian cancer.

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Maurizio Chiriva-Internati

Full Text Available Sperm protein (Sp17 is an attractive target for ovarian cancer (OC vaccines because of its over-expression in primary as well as in metastatic lesions, at all stages of the disease. Our studies suggest that a Sp17-based vaccine can induce an enduring defense against OC development in C57BL/6 mice with ID8 cells, following prophylactic and therapeutic treatments. This is the first time that a mouse counterpart of a cancer testis antigen (Sp17 was shown to be expressed in an OC mouse model, and that vaccination against this antigen significantly controlled tumor growth. Our study shows that the CpG-adjuvated Sp17 vaccine overcomes the issue of immunologic tolerance, the major barrier to the development of effective immunotherapy for OC. Furthermore, this study provides a better understanding of OC biology by showing that Th-17 cells activation and contemporary immunosuppressive T-reg cells inhibition is required for vaccine efficacy. Taken together, these results indicate that prophylactic and therapeutic vaccinations can induce long-standing protection against OC and delay tumor growth, suggesting that this strategy may provide additional treatments of human OC and the prevention of disease onset in women with a family history of OC.

Cancer vaccine THERATOPE- Biomira.

Science.gov (United States)

2003-01-01

Biomira is developing a therapeutic cancer vaccine [THERATOPE] for treatment of breast and other cancers. This profile has been selected from R&D Insight, a pharmaceutical intelligence database produced by Adis International Ltd. THERATOPE consists of the mucin antigen, sialyl-Tn (STn), a carbohydrate located on the surface of breast, colorectal and ovarian cancer cells, conjugated to keyhole limpet haemocyanin (KLH). Merck KGaA has acquired a worldwide licence to THERATOPE for treatment of breast cancer. Under the terms of the licence, Biomira and Merck KGaA, via its US affiliate, EMD Pharmaceuticals, will jointly market the vaccine in the US. Merck KGaA holds exclusive marketing rights for the rest of the world, except in Canada (where Biomira retains rights), Israel and the Palestine Autonomy Area. Merck KGaA is now collaborating on phase III development for breast cancer. Biomira stands to receive $US150 million in licence, milestone payments and equity investments. The development costs will be shared between the two companies in North America but Merck KGaA will be solely responsible for these costs in countries outside the US. Previously, Chiron Corporation had purchased a licence to THERATOPE in 1997; however, Chiron terminated this agreement in June 2000. Under the terms of the termination, Biomira paid Chiron $US2.25 million to compensate the company for its investment in the development of THERATOPE. In addition, Biomira will make another payment of $US3.25 million to Chiron upon FDA approval of the vaccine. No further payments or royalties will be made. In the third quarter of 2002, an independent review of interim data from the trial was conducted. This was the fifth scheduled review of the data by the Independent Data Safety Monitoring Board (DSMB), all of which produced a positive response. Following the completion of the review, the DSMB stated that the trial should continue and that it had no safety concerns regarding this trial. Although the data

Vaccines for Prevention of Cervical Cancer

International Nuclear Information System (INIS)

Mahomed, M.F.

2017-01-01

The characteristics of two prophylactic Human Papilloma Virus HPV vaccines and ethical issues related to HPV vaccination are reviewed in this paper. These vaccines have the potential of substantially reducing HPV-related morbidity and mortality, and in particular cervical cancer. The vaccines cannot treat women with current HPV infection or HPV related disease. They should be administered before the commencement of sexual activity. The ideal age group is adolescent girls between the ages 9-13. Both vaccines are highly efficacious and immunogenic and induce high levels of serum antibodies after three doses for all vaccine-related HPV types. School-based vaccination is considered as a costeffective method for its delivery. Adequate education of both clinicians and patients is an essential to ensure effective implementation when considering a national vaccination program. (author)

RNA Vaccine: novel approach for cancer treatment

OpenAIRE

L K Dwivedi; Prateeksha Goswami; Kanika Bhalla

2011-01-01

Cancer is still an unsolved puzzle and a major cause of mortality and morbidity in the world. Today, about one in every thousand people is dying due to cancer. No effective agent has yet been found which can cure cancer in its metastatic stage. However, attempts in the shape of chemotherapy, immunotherapy and vaccines are made worldwide to find a remedy through a proper regimen. In continuation, tumor specific mRNA has been introduced as part of vaccines in recent days. It is mostly used in t...

Pancreatic cancer vaccine: a unique potential therapy

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Cappello P

2015-12-01

Full Text Available Paola Cappello, Moitza Principe, Francesco Novelli Department of Molecular Biotechnologies and Health Sciences, Center for Experimental Research and Medical Studies, AOU Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy Abstract: Pancreatic ductal adenocarcinoma (PDA is a lethal disease and is one of the cancers that is most resistant to traditional therapies. Historically, neither chemotherapy nor radiotherapy has provided any significant increase in the survival of patients with PDA. Despite intensive efforts, any attempts to improve the survival in the past 15 years have failed. This holds true even after the introduction of molecularly targeted agents, chosen on the basis of their involvement in pathways that are considered to be important in PDA development and progression. Recently, however, FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin treatment has provided a limited survival advantage in patients with advanced PDA. Therefore, effective therapeutic strategies are urgently needed to improve the survival rate of patients with PDA. Results from the last 10 years of research in the field of PDA have helped to identify new immunological targets and develop new vaccines that are capable of stimulating an immune response. In addition, the information obtained about the role of the tumor microenvironment in suppressing the immune response and the possibility of targeting PDA microenvironment to limit immune suppression and enhance the response of effector T-cells has opened new avenues for treating this incurable disease. The time is ripe for developing new therapeutic approaches that are able to effectively counteract the progression and spreading of PDA. This review discusses the potential prospects in the care of patients with pancreatic cancer through vaccination and its combination therapy with surgery, chemotherapy, targeting of the tumor microenvironment, and inhibition of immunological

FDA Approves First Therapeutic Cancer Vaccine

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Sipuleucel-T (Provenge) is a relatively nontoxic treatment option for men with hormone-resistant or castration-resistant prostate cancer. The FDA's approval of the vaccine represented the first proof of principle that immunotherapy can work in cancer.

Vaccines with dendritic cells in prostate cancer patients

International Nuclear Information System (INIS)

Kvalheim, G.

2004-01-01

It has been shown that autologous D Cs pulsed with peptides specific for prostate specific Ag (PSA) or prostate-specific membrane Ag are capable of stimulating potent CT L in vitro. However there is evidence to believe that multiple tumour derived antigens would be more potent to elicit anti-tumour responses. Based on these observations a Phase I/II clinical trial in has been initiated. Autologous monocyte-derived dendritic cells (DC s) were transfected with mRNA from three prostate cancer cell lines (DU145, LNCaP and P C-3) and used for vaccination. Twenty patients have been enrolled and 19 have finished vaccination. Each patient received at least four weekly injections. Of them, 10 patients were vaccinated intranodally under ultrasonic guidance and 9 others received the vaccine intradermally. Safety and feasibility were evaluated. No evidence of toxicity and adverse events was observed. Immune response was measured as DTH and by vitro immunoassays including ELISPOT, T cell proliferation test and cytotoxicity test in pre- and post-vaccination peripheral blood samples. Twelve patients developed a specific immune response to tumour cells. Ten patients showed a significant decrease in log slope PSA. Patients with lower PSA tend to give a better response. The early clinical outcome was significantly related to immune responses (p<0.05). We conclude that the strategy of vaccinating with mRNA transfected D Cs functions to elicit cellular immune responses specific for antigens associated with prostate cancer cells and such responses may result in a clinical benefit for the patients

Breast Cancer Vaccines: New Insights

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Rosaria Benedetti

2017-10-01

Full Text Available Breast cancer (BC is a persistent global challenge for its high frequency in women (although it seldom occurs in men, due to the large diffusion of risk factors and gene mutations, and for its peculiar biology and microenvironment. To date, BC can benefit from different therapeutic strategies involving surgery, ablation, chemotherapy, radiotherapy, and more specific approaches such as hormone therapy and the administration of various substances impairing cancer growth, aggressivity, and recurrence with different modalities. Despite these relatively wide chances, also used in combinatory protocols, relevant mortality and relapse rates, often associated with resistant phenotypes, stress the need for a personalized-medicine based on prompting the patient’s immune system (IS against cancer cells. BC immunogenicity was latterly proven, so the whole immunotherapy field for BC is still at a very early stage. This immunotherapeutic approach exploits both the high specificity of adaptive immune response and the immunological memory. This review is focused on some of the majorly relevant BC vaccines available (NeuVax, AVX901, and INO-1400, providing a description of the more promising clinical trials. The efficacy of cancer vaccines highly depends on the patient’s IS, and a wide optimization is needed in terms of targets’ selection, drug design and combinations, dose finding, protocol structuring, and patients’ recruitment; moreover, new standards are being discussed for the outcome evaluation. However, early-phases excellent results suggest that the manipulation of the IS via specific vaccines is a highly attractive approach for BC.

Combined immunotherapy of breast cancer with EGF and VEGF vaccines from DNA shuffling in a mouse model.

Science.gov (United States)

Jin, Dong; Yu, Xin; Chen, Bing; Li, Zhitao; Ding, Jia; Zhao, Xiuyun; Qi, Gaofu

2017-06-01

Development of EGF and VEGF vaccines with high antigenicity for combined immunotherapy of EGF-EGFR signaling-dependent epithelial tumors such as breast cancer. EGF genes from mouse, human and chicken were randomly assembled to chimeric genes by DNA shuffling, then a chimeric EGF was selected out by PCR, SDS-PAGE and immunization for combined immunotherapy of breast cancer with a previously constructed chimeric VEGF vaccine from shuffling. Combined vaccination with chimeric EGF and VEGF from shuffling could induce high titer of antibodies against EGF and VEGF to inhibit tumor growth and angiogenesis, and improve the survival rate of mice with breast cancer. Combined vaccination with EGF and VEGF from shuffling showed better immunotherapy on EGF-EGFR signaling-dependent epithelial tumors such as breast cancer than the single-agent EGF vaccination.

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.

Elucidating the T-cell reactivity against porcine IDO and RhoC to establish the pig as an animal model for vaccine development against human cancer

DEFF Research Database (Denmark)

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

therapies against cancer, vaccine formulations tailored to mount in vivo CTL responses towards co-delivered cancer antigens will be an important hallmark. Recognition of antigen-derived peptides presented in the context of major histocompatibility complex (MHC) class I molecules on cancer cells......Immune therapy of cancer has recently experienced a great breakthrough with prolonged overall survival in patients with metastatic disease following the use of checkpoint inhibitors and T cell therapy with ex vivo expanded CD8+ cytotoxic T cells (CTLs). In the further development of immune...... is a requirement for activation of CTLs. Previously, the development of therapeutic anti-cancer vaccines have largely been based on rodent models, in particular mice; however the majority of these fail to establish a therapeutic response once put into clinical trials. Pigs have the potential of serving as a model...

Tumor cell-derived microparticles: a new form of cancer vaccine.

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Zhang, Huafeng; Huang, Bo

2015-08-01

For cancer vaccines, tumor antigen availability is currently not an issue due to technical advances. However, the generation of optimal immune stimulation during vaccination is challenging. We have recently demonstrated that tumor cell-derived microparticles (MP) can function as a new form of potent cancer vaccine by efficiently activating type I interferon pathway in a cGAS/STING dependent manner.

Preventive vaccines for cervical cancer

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WHEELER COSETTE M

1997-01-01

Full Text Available The potential use of vaccines for the human papillomavirus (HPV in the prevention and treatment of cervical cancer is a possibility in the near future. Close to 20 genotypes of HPV, of the 75 that have been identified, infect the femine genital tract, but four subtypes (16, 18, 31 and 45 have been associated in close to 80% of cervical cancers. this article proposes that in order to design an effective prophylactic vaccine against HPV infection, an adequate immune response should be guaranteed through four goals; a activation of antigens present in the cell; b overcoming the host response and viral genetic variability in the T cell response; c generation of high levels of T and B memory cells; and d persistence of antigens.

Knowledge on HPV Vaccine and Cervical Cancer Facilitates Vaccine Acceptability among School Teachers in Kitui County, Kenya.

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Moses Muia Masika

Full Text Available Vaccines against human papillomavirus (HPV infection have the potential to reduce the burden of cervical cancer. School-based delivery of HPV vaccines is cost-effective and successful uptake depends on school teachers' knowledge and acceptability of the vaccine. The aim of this study is to assess primary school teachers' knowledge and acceptability of HPV vaccine and to explore facilitators and barriers of an ongoing Gavi Alliance-supported vaccination program in Kitui County, Kenya.This was a cross-sectional, mixed methods study in Central Division of Kitui County where the Ministry of Health is offering the quadrivalent HPV vaccine to grade four girls. Data on primary school teachers' awareness, knowledge and acceptability of HPV vaccine as well as facilitators and barriers to the project was collected through self-administered questionnaires and two focus group discussions.339 teachers (60% female completed the survey (62% response rate and 13 participated in 2 focus group discussions. Vaccine awareness among teachers was high (90%, the level of knowledge about HPV and cervical cancer among teachers was moderate (48%, SD = 10.9 and females scored higher than males (50% vs. 46%, p = 0.002. Most teachers (89% would recommend the vaccine to their daughter or close relatives. Those who would recommend the vaccine had more knowledge than those who would not (p = <0.001. The main barriers were insufficient information about the vaccine, poor accessibility of schools, absenteeism of girls on vaccine days, and fear of side effects.Despite low to moderate levels of knowledge about HPV vaccine among school teachers, vaccine acceptability is high. Teachers with little knowledge on HPV vaccine are less likely to accept the vaccine than those who know more; this may affect uptake if not addressed. Empowering teachers to be vaccine champions in their community may be a feasible way of disseminating information about HPV vaccine and cervical cancer.

Knowledge on HPV Vaccine and Cervical Cancer Facilitates Vaccine Acceptability among School Teachers in Kitui County, Kenya

Science.gov (United States)

Masika, Moses Muia; Ogembo, Javier Gordon; Chabeda, Sophie Vusha; Wamai, Richard G.; Mugo, Nelly

2015-01-01

Background Vaccines against human papillomavirus (HPV) infection have the potential to reduce the burden of cervical cancer. School-based delivery of HPV vaccines is cost-effective and successful uptake depends on school teachers’ knowledge and acceptability of the vaccine. The aim of this study is to assess primary school teachers’ knowledge and acceptability of HPV vaccine and to explore facilitators and barriers of an ongoing Gavi Alliance-supported vaccination program in Kitui County, Kenya. Methods This was a cross-sectional, mixed methods study in Central Division of Kitui County where the Ministry of Health is offering the quadrivalent HPV vaccine to grade four girls. Data on primary school teachers’ awareness, knowledge and acceptability of HPV vaccine as well as facilitators and barriers to the project was collected through self-administered questionnaires and two focus group discussions. Results 339 teachers (60% female) completed the survey (62% response rate) and 13 participated in 2 focus group discussions. Vaccine awareness among teachers was high (90%), the level of knowledge about HPV and cervical cancer among teachers was moderate (48%, SD = 10.9) and females scored higher than males (50% vs. 46%, p = 0.002). Most teachers (89%) would recommend the vaccine to their daughter or close relatives. Those who would recommend the vaccine had more knowledge than those who would not (p = vaccine, poor accessibility of schools, absenteeism of girls on vaccine days, and fear of side effects. Conclusions Despite low to moderate levels of knowledge about HPV vaccine among school teachers, vaccine acceptability is high. Teachers with little knowledge on HPV vaccine are less likely to accept the vaccine than those who know more; this may affect uptake if not addressed. Empowering teachers to be vaccine champions in their community may be a feasible way of disseminating information about HPV vaccine and cervical cancer. PMID:26266949

Identification of a microRNA signature in dendritic cell vaccines for cancer immunotherapy

DEFF Research Database (Denmark)

Holmstrøm, Kim; Pedersen, Ayako Wakatsuki; Claesson, Mogens Helweg

2010-01-01

Dendritic cells (DCs) exposed to tumor antigens followed by treatment with T(h)1-polarizing differentiation signals have paved the way for the development of DC-based cancer vaccines. Critical parameters for assessment of the optimal functional state of DCs and prediction of the vaccine potency o...

Racial and ethnic disparities in human papillomavirus-associated cancer burden with first-generation and second-generation human papillomavirus vaccines.

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Burger, Emily A; Lee, Kyueun; Saraiya, Mona; Thompson, Trevor D; Chesson, Harrell W; Markowitz, Lauri E; Kim, Jane J

2016-07-01

In the United States, the burden of human papillomavirus (HPV)-associated cancers varies by racial/ethnic group. HPV vaccination may provide opportunities for primary prevention of these cancers. Herein, the authors projected changes in HPV-associated cancer burden among racial/ethnic groups under various coverage assumptions with the available first-generation and second-generation HPV vaccines to evaluate changes in racial/ethnic disparities. Cancer-specific mathematical models simulated the burden of 6 HPV-associated cancers. Model parameters, informed using national registries and epidemiological studies, reflected sex-specific, age-specific, and racial/ethnic-specific heterogeneities in HPV type distribution, cancer incidence, stage of disease at detection, and mortality. Model outcomes included the cumulative lifetime risks of developing and dying of 6 HPV-associated cancers. The level of racial/ethnic disparities was evaluated under each alternative HPV vaccine scenario using several metrics of social group disparity. HPV vaccination is expected to reduce the risks of developing and dying of HPV-associated cancers in all racial/ethnic groups as well as reduce the absolute degree of disparities. However, alternative metrics suggested that relative disparities would persist and in some scenarios worsen. For example, when assuming high uptake with the second-generation HPV vaccine, the lifetime risk of dying of an HPV-associated cancer for males decreased by approximately 60%, yet the relative disparity increased from 3.0 to 3.9. HPV vaccines are expected to reduce the overall burden of HPV-associated cancers for all racial/ethnic groups and to reduce the absolute disparity gap. However, even with the second-generation vaccine, relative disparities will likely still exist and may widen if the underlying causes of these disparities remain unaddressed. Cancer 2016;122:2057-66. © 2016 American Cancer Society. © 2016 American Cancer Society.

Prevalence of HPV 16 and 18 and attitudes toward HPV vaccination trials in patients with cervical cancer in Mali

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Téguété, Ibrahima; Dolo, Amadou; Sangare, Kotou; Sissoko, Abdoulaye; Rochas, Mali; Beseme, Sarah; Tounkara, Karamoko; Yekta, Shahla; De Groot, Anne S.; Koita, Ousmane A.

2017-01-01

Background Cervical cancer is one of the most common and lethal cancers in West Africa. Even though vaccines that protect against the most common Human papillomavirus (HPV) strains, 16 and 18, are currently in use in developed countries, the implementation of these vaccines in developing countries has been painfully slow, considering the pre-eminence of HPV-associated cervical cancer among women in those countries. Aim We performed serological and PCR-based assessment of blood and tissue specimens obtained from women undergoing cervical cancer-related surgery at a major urban hospital in Bamako. Since several therapeutic HPV vaccines are currently in clinical trials, we also assessed willingness to participate in HPV cancer vaccine trials. Methods Blood and biopsy samples of 240 women were evaluated for HPV types 16 and 18 by serology and PCR. Knowledge regarding the HPV vaccine and autonomy to decide to vaccinate their own child was assessed with a standardized questionnaire. Results HPV 16 and 18 were identified in 137/166 (82.5%) cervical cancer biopsy samples by PCR. Co-infection with both HPV 16 and 18 was significantly more frequent in women over 50 years of age than in younger women (63.0% vs. 37.0%). 44% of study participants said they would be willing to vaccinate their child with HPV vaccine. Only 39% of women participating in this study reported that they would be able to make an autonomous decision to receive HPV vaccination. Permission from a male spouse or head of household was identified as important for participation by 59% of the women. Conclusion This study provides strong support for the introduction of currently available HPV vaccines in Mali, and also provides key information about conditions for obtaining informed consent for HPV vaccine trials and HPV vaccination in Mali. PMID:28231334

Cyclooxygenase-2 inhibitor enhances the efficacy of a breast cancer vaccine: role of IDO.

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Basu, Gargi D; Tinder, Teresa L; Bradley, Judy M; Tu, Tony; Hattrup, Christine L; Pockaj, Barbara A; Mukherjee, Pinku

2006-08-15

We report that administration of celecoxib, a specific cyclooxygenase-2 (COX-2) inhibitor, in combination with a dendritic cell-based cancer vaccine significantly augments vaccine efficacy in reducing primary tumor burden, preventing metastasis, and increasing survival. This combination treatment was tested in MMTV-PyV MT mice that develop spontaneous mammary gland tumors with metastasis to the lungs and bone marrow. Improved vaccine potency was associated with an increase in tumor-specific CTLs. Enhanced CTL activity was attributed to a significant decrease in levels of tumor-associated IDO, a negative regulator of T cell activity. We present data suggesting that inhibiting COX-2 activity in vivo regulates IDO expression within the tumor microenvironment; this is further corroborated in the MDA-MB-231 human breast cancer cell line. Thus, a novel mechanism of COX-2-induced immunosuppression via regulation of IDO has emerged that may have implications in designing future cancer vaccines.

Cancer treatment: the combination of vaccination with other therapies

DEFF Research Database (Denmark)

Andersen, M.H.; Sorensen, R.B.; Schrama, D.

2008-01-01

approach to fight cancer, the combination with additional therapy could create a number of synergistic effects. Herein we discuss the possibilities and prospects of vaccination when combined with other treatments. In this regard, cell death upon drug exposure may be immunogenic or non-immunogenic depending...... and endothelial cells. The efficacy of therapeutic vaccination against cancer will over the next few years be studied in settings taking advantage of strategies in which vaccination is combined with other treatment modalities. These combinations should be based on current knowledge not only regarding the biology...... of the cancer cell per se, but also considering how treatment may influence the malignant cell population as well as the immune system Udgivelsesdato: 2008/11...

NIH Research Leads to Cervical Cancer Vaccine

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... Issues Sexually Transmitted Diseases NIH Research Leads to Cervical Cancer Vaccine Past Issues / Fall 2008 Table of Contents ... in women, the cause of the majority of cervical cancers. Photo courtesy of Judy Folkenberg, NLM Writer By ...

Embryonic vaccines against cancer: an early history.

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Brewer, Bradley G; Mitchell, Robert A; Harandi, Amir; Eaton, John W

2009-06-01

Almost 100 years have passed since the seminal observations of Schöne showing that vaccination of animals with fetal tissue would prevent the growth of transplantable tumors. Many subsequent reports have affirmed the general idea that immunologic rejection of transplantable tumors, as well as prevention of carcinogenesis, may be affected by vaccination with embryonic/fetal material. Following a decade of intense research on this phenomenon during approximately 1964-1974, interest appears to have waned. This earlier experimental work may be particularly pertinent in view of the rising interest in so-called cancer stem cells. We believe that further work - perhaps involving the use of embryonic stem cells as immunogens - is warranted and that the results reviewed herein support the concept that vaccination against the appearance of cancers of all kinds is a real possibility.

Mothers' knowledge and attitudes about HPV vaccination to prevent cervical cancers.

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Kose, Dilek; Erkorkmaz, Unal; Cinar, Nursan; Altinkaynak, Sevin

2014-01-01

Cervical cancer which is one of the most preventable cancers is an important public health problem worldwide, and especially in developing countries. The aim of this study was to determine knowledge and attitudes about the HPV vaccination of mothers with 0- to 18-year old children. Written approval was taken from the local authorities. The study subjects consisted of 799 mothers who agreed to participate. The data were collected via a "Personal Information Form" which included 30 questions that were prepared by the researchers themselves in line with the literature. The data were collected by face to face interviews with the mothers. Analyses were performed using commercial software. The mean age of the mothers who participated in the study was 32.0 ± 6.52, and 88.1% reported no information about HPV, and 83.5% no information about HPV vaccination. Only 0.7% of the mothers had daughters who had HPV vaccination, and 44.3% of the mothers who had sons were found out to be indecisive about having HPV vaccination. There was a significant corelation between the educational status of the mothers and their knowledge about HPV vaccination (p0.05). This study suggested that mothers had very little information on HPV and HPV vaccination. Knowledge of the disease and its vaccination is an essential factor for the success of the vaccination program. It is of great importance that mothers are trained in this subject by health professionals.

Epidemiology of HPV 16 and cervical cancer in Finland and the potential impact of vaccination: mathematical modelling analyses.

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Ruanne V Barnabas

2006-05-01

Full Text Available BACKGROUND: Candidate human papillomavirus (HPV vaccines have demonstrated almost 90%-100% efficacy in preventing persistent, type-specific HPV infection over 18 mo in clinical trials. If these vaccines go on to demonstrate prevention of precancerous lesions in phase III clinical trials, they will be licensed for public use in the near future. How these vaccines will be used in countries with national cervical cancer screening programmes is an important question. METHODS AND FINDINGS: We developed a transmission model of HPV 16 infection and progression to cervical cancer and calibrated it to Finnish HPV 16 seroprevalence over time. The model was used to estimate the transmission probability of the virus, to look at the effect of changes in patterns of sexual behaviour and smoking on age-specific trends in cancer incidence, and to explore the impact of HPV 16 vaccination. We estimated a high per-partnership transmission probability of HPV 16, of 0.6. The modelling analyses showed that changes in sexual behaviour and smoking accounted, in part, for the increase seen in cervical cancer incidence in 35- to 39-y-old women from 1990 to 1999. At both low (10% in opportunistic immunisation and high (90% in a national immunisation programme coverage of the adolescent population, vaccinating women and men had little benefit over vaccinating women alone. We estimate that vaccinating 90% of young women before sexual debut has the potential to decrease HPV type-specific (e.g., type 16 cervical cancer incidence by 91%. If older women are more likely to have persistent infections and progress to cancer, then vaccination with a duration of protection of less than 15 y could result in an older susceptible cohort and no decrease in cancer incidence. While vaccination has the potential to significantly reduce type-specific cancer incidence, its combination with screening further improves cancer prevention. CONCLUSIONS: HPV vaccination has the potential to

Clinical responses in patients with advanced colorectal cancer to a dendritic cell based vaccine

DEFF Research Database (Denmark)

Burgdorf, Stefan K; Fischer, Anders; Myschetzky, Peter S

2008-01-01

Patients with disseminated colorectal cancer have a poor prognosis. Preliminary studies have shown encouraging results from vaccines based on dendritic cells. The aim of this phase II study was to evaluate the effect of treating patients with advanced colorectal cancer with a cancer vaccine based...... with this DC-based cancer vaccine was safe and non-toxic. Stable disease was found in 24% (4/17) of the patients. The quality of life remained for most categories high and stable throughout the study period.......Patients with disseminated colorectal cancer have a poor prognosis. Preliminary studies have shown encouraging results from vaccines based on dendritic cells. The aim of this phase II study was to evaluate the effect of treating patients with advanced colorectal cancer with a cancer vaccine based......-testis antigens. Vaccines were biweekly administered intradermally with a total of 10 vaccines per patient. CT scans were performed and responses were graded according to the RECIST criteria. Quality of life was monitored with the SF-36 questionnaire. Toxicity and adverse events were graded according...

Cost-effectiveness of human papillomavirus vaccination for prevention of cervical cancer in Taiwan

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Chow Song-Nan

2010-01-01

Full Text Available Abstract Background Human papillomavirus (HPV infection has been shown to be a major risk factor for cervical cancer. Vaccines against HPV-16 and HPV-18 are highly effective in preventing type-specific HPV infections and related cervical lesions. There is, however, limited data available describing the health and economic impacts of HPV vaccination in Taiwan. The objective of this study was to assess the cost-effectiveness of prophylactic HPV vaccination for the prevention of cervical cancer in Taiwan. Methods We developed a Markov model to compare the health and economic outcomes of vaccinating preadolescent girls (at the age of 12 years for the prevention of cervical cancer with current practice, including cervical cytological screening. Data were synthesized from published papers or reports, and whenever possible, those specific to Taiwan were used. Sensitivity analyses were performed to account for important uncertainties and different vaccination scenarios. Results Under the assumption that the HPV vaccine could provide lifelong protection, the massive vaccination among preadolescent girls in Taiwan would lead to reduction in 73.3% of the total incident cervical cancer cases and would result in a life expectancy gain of 4.9 days or 8.7 quality-adjusted life days at a cost of US$324 as compared to the current practice. The incremental cost-effectiveness ratio (ICER was US$23,939 per life year gained or US$13,674 per quality-adjusted life year (QALY gained given the discount rate of 3%. Sensitivity analyses showed that this ICER would remain below US$30,000 per QALY under most conditions, even when vaccine efficacy was suboptimal or when vaccine-induced immunity required booster shots every 13 years. Conclusions Although gains in life expectancy may be modest at the individual level, the results indicate that prophylactic HPV vaccination of preadolescent girls in Taiwan would result in substantial population benefits with a favorable cost

Modeling Cervical Cancer Prevention in Developed Countries

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Kim, Jane J.; Brisson, Marc; Edmunds, W. John; Goldie, Sue J.

2009-01-01

Cytology-based screening has reduced cervical cancer mortality in countries able to implement, sustain and financially support organized programs that achieve broad coverage. These ongoing secondary prevention efforts considerably complicate the question of whether vaccination against Human Papillomavirus (HPV) types -16 and 18 should be introduced. Policy questions focus primarily on the target ages of vaccination, appropriate ages for a temporary “catch-up” program, possible revisions in screening policies to optimize synergies with vaccination, including the increased used of HPV DNA testing, and the inclusion of boys in the vaccination program. Decision-analytic models are increasingly being developed to simulate disease burden and interventions in different settings in order to evaluate the benefits and cost-effectiveness of primary and secondary interventions for informed decision-making. This article is a focused review on existing mathematical models that have been used to evaluate HPV vaccination in the context of developed countries with existing screening programs. Despite variations in model assumptions and uncertainty in existing data, pre-adolescent vaccination of girls is consistently found to be attractive in the context of current screening practices, provided there is complete and lifelong vaccine protection and widespread vaccination coverage. Questions related to catch-up vaccination programs, potential benefits of other non-cervical cancer outcomes and inclusion of boys are subject to far more uncertainty, and results from these analyses have reached conflicting conclusions. Most analyses find that some catch-up vaccination is warranted but becomes increasingly unattractive as the catch-up age is extended, and vaccination of boys is unlikely to be cost-effective if reasonable levels of coverage are achieved in girls or coverage among girls can be improved. The objective of the review is to highlight points of consensus and qualitative

Vaccines against human papilloma virus and cervical cancer: An overview

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Sharma Savita

2008-01-01

Full Text Available The paradigm of preventing human papilloma virus (HPV infection through currently approved vaccines, namely, Gardasil, manufactured by Merck and Co., Inc. (Whitehouse Station, NJ and Cervarix, manufactured by GlaxoSmithKline (GSK, Philadelphia holds tremendous promise for the developing countries in decreasing the burden of HPV infection and its sequelae, such as cervical cancer, genital warts and anogenital cancers. Effective screening programs that have reduced the burden of this killer disease in the developed countries are still lacking in India, despite the high incidence of cervical cancer and the implementation of the National Cancer Control Programme since 1975. The recent breakthrough in the global war against cervical cancer will provide new insight for meeting the future challenge of the prevention of cervical cancer in India.

Human Papillomavirus-mediated cervical cancer awareness and Gardasil vaccination: a pilot survey among North Indian women.

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Pandey, Saumya; Chandravati

2013-10-01

Human Papillomavirus (HPV)-mediated cervical cancer is a leading cause of morbidity and mortality in women worldwide, including Indian women. Cervical cancer control and prevention strategies are being adopted in developing nations to reduce the increasing burden of HPV infection in the vaccine era. The present study, therefore, aimed to evaluate cervical cancer awareness and knowledge of Gardasil vaccination in North Indian women. A pilot survey was conducted among 103 women of North Indian ethnicity residing in Lucknow/adjoining areas in state of Uttar Pradesh, during routine screening/clinic visits from June 2012 to December 2012. The study subjects were interviewed in either Hindi or English; subsequently the awareness of HPV-mediated cervical cancer and knowledge of Gardasil vaccination was assessed in terms of "yes", "no" and "no response". The study was approved by the Institutional Review Board. Written informed consent was taken from the participants. Overall, the response of participants (n = 103) in our single-centre survey-based pilot study was well-defined. The response regarding HPV-mediated cervical cancer awareness in terms of "yes", "no" and "no response" among the study subjects was 43.7, 44.7 and 11.6 %, respectively. Furthermore, in response to knowledge of HPV vaccine Gardasil, out of 103 subjects, 28.1 % answered "yes" while 37.9 and 34.0 % stated "no" and "no response", respectively. Our pilot survey may help in assessing knowledge of HPV-mediated cervical cancer and Gardasil vaccination awareness in women, and accordingly develop cost-effective cervical cancer control and prevention/public health counseling sessions in a clinical setting.

Tailoring DNA vaccines: designing strategies against HER2 positive cancers

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Cristina eMarchini

2013-05-01

Full Text Available The crucial role of HER2 in epithelial transformation and its selective overexpression on cancer tissues makes it an ideal target for cancer immunotherapies such as passive immunotherapy with Trastuzumab. There are, however, a number of concerns regarding the use of monoclonal antibodies which include resistance, repeated treatments, considerable costs and side effects that make active immunotherapies against HER2 desirable alternative approaches. The efficacy of anti-HER2 DNA vaccination has been widely demonstrated in transgenic cancer-prone mice, which recapitulate several features of human breast cancers. Nonetheless, the rational design of a cancer vaccine able to trigger a long lasting immunity, and thus prevent tumor recurrence in patients, would require the understanding of how tolerance and immunosuppression regulate antitumor immune responses and, at the same time, the identification of the most immunogenic portions of the target protein. We herein retrace the findings that led to our most promising DNA vaccines that, by encoding human/rat chimeric forms of HER2, are able to circumvent peripheral tolerance. Preclinical data obtained with these chimeric DNA vaccines have provided the rationale for their use in an ongoing phase I clinical trial (EudraCT 2011-001104-34.

Knowledge, Awareness and Attitude on HPV, HPV Vaccine and Cervical Cancer among the College Students in India.

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Rashid, Shazia; Labani, Satyanarayana; Das, Bhudev C

2016-01-01

Infection of specific high risk Human papillomaviruses (HPVs) is known to cause cervical cancer and two prophylactic vaccines have been developed against two major high risk HPV types 16 and 18 for prevention of cervical cancer. Because of societal, religious and ethical issues associated with the vaccination of adolescent girls in India together with lack of awareness about HPV and HPV vaccines, no successful HPV immunization program has been employed in India. To determine knowledge, awareness and attitude of college students on HPV, HPV vaccine and cervical cancer. A questionnaire-based survey was conducted in a total of 1580 undergraduate students between the age group 16-26 years comprising 684 girls and 876 boys. Out of a total of 1580 students, girls had more knowledge about cervical cancer (82.45%, pawareness about cervical cancer (81.89%, pawareness compared to boys. Analysis of odds ratio (ORs) along with 95% CI showed older girls with 1.2 to 3 fold (pawareness campaigns to augment HPV immunization program for control of cervical cancer in India.

Vaccination with apoptosis colorectal cancer cell pulsed autologous ...

African Journals Online (AJOL)

user

2011-02-18

Feb 18, 2011 ... with DCs vaccine to assess toxicity, tolerability, immune and clinical responses to the vaccine. No ... Key words: Dendritic cells, immunotherapy, colorectal cancer. .... color analyses of DCs, cells were labeled simultaneously with ..... promote CD8+ Tc1 cell survival, memory response, tumor localization and ...

Knowledge about Human Papillomavirus and Cervical Cancer: Predictors of HPV Vaccination among Dental Students

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Rajiah, Kingston; Maharajan, Mari Kannan; Fang Num, Kelly Sze; How Koh, Raymond Chee

2017-06-25

Background: The objective of this study is to determine the influence of dental students’ knowledge and attitude regarding human papillomavirus infection of cervical cancer on willingness to pay for vaccination. Basic research design: A convenience sampling method was used. The minimal sample size of 136 was calculated using the Raosoft calculator with a 5 % margin of error and 95% confidence level. Participants: The study population were all final year dental students from the School of Dentistry. Methods: A self-administered questionnaire was used to measure knowledge levels and attitudes regarding human papillomavirus vaccination. Contingent valuation was conducted for willingness to pay for vaccination. Main outcome measures: The Center for Disease Control and Prevention has stated that human papillomavirus are associated with oropharynx cancer and the American Dental Association insist on expanding public awareness of the oncogenic potential of some HPV infections. Thus, as future dental practitioners, dental students should be aware of human papillomavirus and their links with cancer and the benefits of vaccination. Results: Knowledge on HPV and cervical cancer did not impact on attitudes towards vaccines. However, significant correlation existed between knowledge and willingness to pay for vaccination. Conclusions: Dental students’ knowledge on HPV and cervical cancer has no influence on their attitude towards HPV vaccines. However, their willingness to pay for HPV vaccination is influenced by their knowledge of cervical cancer and HPV vaccination. Creative Commons Attribution License

Human Papilloma Virus associated with oral cancer and preventive strategies: the role of vaccines.

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Ottria, L; Candotto, V; Cura, F; Baggi, L; Arcuri, C; Nardone, M; Gaudio, R M; Gatto, R; Spadari, F; Carinci, F

2018-01-01

The aim of this paper is to describe the efficacy of Human Papilloma Virus (HPV) vaccines for preventing oral cancer. A systematic review of the literature was conducted to describe the state of the art about HPV vaccines for preventing oral cancer. The aspects of prevention and control of infection by administering vaccines and the diffusion of sexual education campaigns are discussed also. In recent years there has been a growing interest in HPV in dentistry, suggesting a role of such a family of viruses in the development of oral cancers as well as of the uterine cervix. Even if the mass media have increasingly faced the problem, causing frequent alarming among patients, the dentist therefore needs a complete and up-to-date knowledge of this infectious condition that is one of the most common causes of sexually transmitted mucous membrane infections (eg genital, anal and oral). Recent studies about HPV infection are a basic requirement in order to promote the HPV vaccinations and patient’s health.

The human papillomavirus vaccine: A powerful tool for the primary prevention of cervical cancer.

OpenAIRE

Nubia Muñoz; Julio César Reina; Gloria Inés Sánchez

2009-01-01

Prophylactic human papillomavirus (HPV) vaccine is the most promissory public health tool for primary prevention of cervical cancer. Immunization of females before the acquisition of HPV infection has the greatest impact in preventing pre-neoplasic lesions and cervical cancer. Current HPV vaccines do not eliminate cervical cancer risk, therefore, screening should continue covering vaccinated as well as women that do not get the vaccine. The strategies that include combination of high-coverage...

Knowledge of Human Papillomavirus Infection, Cervical Cancer and Willingness to pay for Cervical Cancer Vaccination among Ethnically Diverse Medical Students in Malaysia.

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Maharajan, Mari Kannan; Rajiah, Kingston; Num, Kelly Sze Fang; Yong, Ng Jin

2015-01-01

The primary objective of this study was to assess the knowledge of medical students and determine variation between different cultural groups. A secondary aim was to find out the willingness to pay for cervical cancer vaccination and the relationships between knowledge and attitudes towards Human Papillomavirus vaccination. A cross-sectional survey was conducted in a private medical university between June 2014 and November 2014 using a convenient sampling method. A total of 305 respondents were recruited and interviewed with standard questionnaires for assessment of knowledge, attitudes and practice towards human papilloma virus and their willingness to pay for HPV vaccination. Knowledge regarding human papilloma virus, human papilloma virus vaccination, cervical cancer screening and cervical cancer risk factors was good. Across the sample, a majority (90%) of the pupils demonstrated a high degree of knowledge about cervical cancer and its vaccination. There were no significant differences between ethnicity and the participants' overall knowledge of HPV infection, Pap smear and cervical cancer vaccination. Some 88% of participants answered that HPV vaccine can prevent cervical cancer, while 81.5% of medical students said they would recommend HPV vaccination to the public although fewer expressed an intention to receive vaccination for themselves.

Clinical development of Ebola vaccines

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Sridhar, Saranya

2015-01-01

The ongoing outbreak of Ebola virus disease in West Africa highlighted the lack of a licensed drug or vaccine to combat the disease and has renewed the urgency to develop a pipeline of Ebola vaccines. A number of different vaccine platforms are being developed by assessing preclinical efficacy in animal models and expediting clinical development. Over 15 different vaccines are in preclinical development and 8 vaccines are now in different stages of clinical evaluation. These vaccines include DNA vaccines, virus-like particles and viral vectors such as live replicating vesicular stomatitis virus (rVSV), human and chimpanzee adenovirus, and vaccinia virus. Recently, in preliminary results reported from the first phase III trial of an Ebola vaccine, the rVSV-vectored vaccine showed promising efficacy. This review charts this rapidly advancing area of research focusing on vaccines in clinical development and discusses the future opportunities and challenges faced in the licensure and deployment of Ebola vaccines. PMID:26668751

Nanotechnology Laboratory Collaborates with Army to Develop Botulism Vaccine | FNLCR

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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

Cost-effectiveness of human papillomavirus vaccination and cervical cancer screening in Thailand.

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Sharma, M; Ortendahl, J; van der Ham, E; Sy, S; Kim, J J

2012-01-01

To assess the health and economic outcomes of various screening and vaccination strategies for cervical cancer prevention. Cost-effectiveness analysis from a societal perspective. Thailand. Females aged 9 years and older. Using a mathematical model of human papillomavirus (HPV) infection and cervical cancer, calibrated to epidemiological data from Thailand, we estimated the cost-effectiveness of pre-adolescent HPV vaccination, screening [visual inspection with acetic acid (VIA), HPV DNA testing, and cytology] between one and five times per lifetime in adulthood, and combined pre-adolescent vaccination and screening. Vaccine efficacy, coverage, cost, and screening frequency were varied in sensitivity analyses. Incremental cost-effectiveness ratios, expressed as cost per year of life saved (YLS). Assuming lifelong efficacy and 80% coverage, pre-adolescent HPV vaccination alone was projected to reduce the lifetime risk of cervical cancer by 55%, which was greater than any strategy of screening alone. When cost per vaccinated girl was I$10 (approximately $2 per dose) or less, HPV vaccination alone was cost saving. Pre-adolescent vaccination and HPV DNA testing five times per lifetime, starting at age 35 years, reduced the lifetime cervical cancer risk by 70%, and had a cost-effectiveness ratio less than Thailand's GDP per capita (I$8100), provided the cost per vaccinated girl was I$200 or less. Low cost pre-adolescent HPV vaccination followed by HPV screening five times per lifetime is an efficient strategy for Thailand. Costs may need to be lower, however, for this strategy to be affordable. If vaccination is not feasible, HPV DNA testing five times per lifetime is efficient. © 2011 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2011 RCOG.

Human papillomavirus vaccine and cervical cancer prevention: practice and policy implications for pharmacists.

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McIntosh, Jennifer; Sturpe, Deborah A; Khanna, Niharika

2008-01-01

To review the epidemiology and natural history of human papillomavirus (HPV), summarize relevant clinical trials of the prophylactic HPV vaccines, and describe the practice and policy implications that HPV vaccine represents for pharmacists. Search of Medline through June 2007 using keywords human papillomavirus vaccine, Gardasil, and Cervarix; meeting abstracts; bibliographies from selected articles; and National Institutes of Health clinical trials registry. English language review articles, clinical trials, and published abstracts were considered for inclusion. HPV is a sexually transmitted infection that is necessary for the development of cervical cancer, and types 16 and 18 are associated with 70% of cases of invasive cervical cancer worldwide. A quadrivalent prophylactic vaccine against HPV-6, -11, -16, and -18 is currently available, and a bivalent vaccine targeting HPV-16 and -18 is under review by the Food and Drug Administration. Both are highly effective at preventing persistent HPV infection and precancerous lesions caused by vaccine-specific HPV. HPV vaccine is currently indicated for girls aged 9 to 26 years, but ongoing trials are evaluating the efficacy in other populations. Implementation of a vaccine administration program is an area of opportunity for new policies to include pharmacists in the administration of prophylactic HPV vaccines. Pharmacists are allowed to administer vaccinations in 46 states and can potentially play a role in HPV vaccine administration. For this to happen, however, multiple legal and regulatory changes must occur. Prophylactic HPV vaccines safely and effectively prevent HPV infection and precancerous lesions in the cervix. The availability of these vaccines also create new clinical opportunities for community pharmacists, provided needed legal, regulatory, and policy changes are made.

Vaccine-associated sarcomas in cats: a unique cancer model.

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McNiel, E A

2001-01-01

Epidemiologic evidence supports a relationship between vaccination of cats for rabies and feline leukemia virus with the development of soft tissue sarcomas at the site of administration. These tumors are locally invasive and histologically aggressive. As with high-grade soft tissue sarcoma in humans, combination treatment with radiation therapy and surgery provides for optimum tumor control. Feline vaccine-associated sarcoma has become a difficult issue for the veterinary profession for legal, ethical, and clinical reasons. Although most research efforts have focused on therapeutic intervention, this tumor has great potential to provide an informative model for carcinogenesis and genetic susceptibility applicable to cancer in all species, including humans.

Evolution of the health economics of cervical cancer vaccination

NARCIS (Netherlands)

Ferko, Nicole; Postma, Maarten; Gallivan, Steve; Kruzikas, Denise; Drummond, Michael

2008-01-01

This paper reviews the history of modelling for cervical cancer vaccination. We provide an interpretation and summary of conclusions pertaining to the usefulness of different models, the predicted epidemiological impact of vaccination and the cost-effectiveness of adolescent, catch-up and

Clinical application of dendritic cells in cancer vaccination therapy

DEFF Research Database (Denmark)

Svane, Inge Marie; Soot, Mette Line; Buus, Søren

2003-01-01

During the last decade use of dendritic cells (DC) has moved from murine and in vitro studies to clinical trials as adjuvant in cancer immunotherapy. Here they function as delivery vehicles for exogenous tumor antigens, promoting an efficient antigen presentation. The development of protocols...... for large-scale generation of dendritic cells for clinical applications has made possible phase I/II studies designed to analyze the toxicity, feasibility and efficacy of this approach. In clinical trials, DC-based vaccination of patients with advanced cancer has in many cases led to immunity...

Prevalence and Predictors of Human Papillomavirus (HPV) Vaccination among Young Women Surviving Childhood Cancer

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Klosky, James L.; Favaro, Brianne; Peck, Kelly R.; Simmons, Jessica L.; Russell, Kathryn M.; Green, Daniel M.; Hudson, Melissa M.

2015-01-01

Purpose Human papillomavirus (HPV) is a sexually transmitted infection and the cause of cervical and other cancers. Vaccination is available to protect against genital HPV and is recommended for individuals aged 9-26 years. This study aimed to estimate the prevalence of HPV vaccination among childhood cancer survivors and to identify factors associated with vaccine outcomes. Methods Young adult females with (n = 114; M age =21.18 years, SD =2.48) and without (n = 98; M age = 20.65 years, SD = 2.29) a childhood cancer history completed surveys querying HPV vaccination initiation/completion, as well as sociodemographic, medical, and health belief factors. Multivariable logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI) for vaccine outcomes. Results Among survivors, 38.6% (44/114) and 26.3% (30/114) initiated or completed vaccination compared to 44.9% (44/98) and 28.6% (28/98) among controls, respectively. In the combined survivor/control group, physician recommendation (OR = 11.24, 95% CI, 3.15 – 40.14), and familial HPV communication (OR = 7.28, 95% CI, 1.89 – 28.05) associated with vaccine initiation. Perceptions of vaccine benefit associated with vaccine completion (OR = 10.55, 95% CI, 1.59 – 69.92), whereas perceptions of HPV-related severity associated with non-completion (OR = 0.14, 95% CI, 0.03 – 0.71). Conclusion Despite their increased risk for HPV-related complication, a minority of childhood cancer survivors have initiated or completed HPV vaccination. Modifiable factors associating with vaccine outcomes were identified. Implications HPV vaccination is a useful tool for cancer prevention in survivorship, and interventions to increase vaccine uptake are warranted. PMID:26572902

Change in knowledge of women about cervix cancer, human papilloma virus (HPV) and HPV vaccination due to introduction of HPV vaccines.

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Donders, Gilbert G G; Bellen, Gert; Declerq, Ann; Berger, Judith; Van Den Bosch, Thierry; Riphagen, Ine; Verjans, Marcel

2009-07-01

Test knowledge of HPV, cervix cancer awareness and acceptance of HPV vaccination of women now and a year ago. Questionnaires were filled out by 305 women visiting four gynaecologists of the Regional Hospital Heilig Hart, Tienen, Belgium during two subsequent weeks. Fisher T or Chi(2) were used as statistical methods to compare the data with the survey of 381 women exactly one year before. Knowledge about HPV as a cause of cervix cancer and the presence of a vaccine rose from roughly 50% in 2007 to over 80% in 2008 (pwomen below 26 years had now acquired almost equivalent knowledge to older women about the virus, cervix cancer and the vaccine, but they were far less likely to accept the vaccine due to its cost, unless it would be reimbursed (OR 4.2 (1.6-11) p=0.0055). One year after introduction of the first two HPV vaccines, over 75% of women attending an ambulatory gynaecology clinic know HPV causes cervix cancer and that you can get vaccinated against it. Compared with a year earlier, young and lower educated women had dramatically improved their knowledge. However, women below 26 years are less prepared to pay the cost for vaccination if it is not reimbursed.

Dendritic cell-based vaccination in cancer: therapeutic implications emerging from murine models

Directory of Open Access Journals (Sweden)

Soledad eMac Keon

2015-05-01

Full Text Available Dendritic cells (DCs play a pivotal role in the orchestration of immune responses, and are thus key targets in cancer vaccine design. Since the 2010 FDA approval of the first cancer DC-based vaccine (Sipuleucel T there has been a surge of interest in exploiting these cells as a therapeutic option for the treatment of tumors of diverse origin. In spite of the encouraging results obtained in the clinic, many elements of DC-based vaccination strategies need to be optimized. In this context, the use of experimental cancer models can help direct efforts towards an effective vaccine design. This paper reviews recent findings in murine models regarding the antitumoral mechanisms of DC-based vaccination, covering issues related to antigen sources, the use of adjuvants and maturing agents, and the role of DC subsets and their interaction in the initiation of antitumoral immune responses. The summary of such diverse aspects will highlight advantages and drawbacks in the use of murine models, and contribute to the design of successful DC-based translational approaches for cancer treatment.

Cervical Cancer Incidence in Young U.S. Females After Human Papillomavirus Vaccine Introduction.

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Guo, Fangjian; Cofie, Leslie E; Berenson, Abbey B

2018-05-30

Since 2006, human papillomavirus vaccine has been recommended for young females in the U.S. This study aimed to compare cervical cancer incidence among young women before and after the human papillomavirus vaccine was introduced. This cross-sectional study used data from the National Program for Cancer Registries and Surveillance, Epidemiology, and End Results Incidence-U.S. Cancer Statistics 2001-2014 database for U.S. females aged 15-34 years. This study compared the 4-year average annual incidence of invasive cervical cancer in the 4 years before human papillomavirus vaccine was introduced (2003-2006) and the 4 most recent years in the vaccine era (2011-2014). Joinpoint regression models of cervical incidence from 2001 to 2014 were fitted to identify the discrete joints (year) that represent statistically significant changes in the direction of the trend after the introduction of human papillomavirus vaccination in 2006. Data were collected in 2001-2014, released, and analyzed in 2017. The 4-year average annual incidence rates for cervical cancer in 2011-2014 were 29% lower than that in 2003-2006 (6.0 vs 8.4 per 1,000,000 people, rate ratio=0.71, 95% CI=0.64, 0.80) among females aged 15-24 years, and 13.0% lower among females aged 25-34 years. Joinpoint analyses of cervical cancer incidence among females aged 15-24 years revealed a significant joint at 2009 for both squamous cell carcinoma and non-squamous cell carcinoma. Among females aged 25-34 years, there was no significant decrease in cervical cancer incidence after 2006. A significant decrease in the incidence of cervical cancer among young females after the introduction of human papillomavirus vaccine may indicate early effects of human papillomavirus vaccination. Copyright © 2018 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Progress of dendritic cell-based cancer vaccines for patients with hematological malignancies.

Science.gov (United States)

Ni, Ming; Hoffmann, Jean-Marc; Schmitt, Michael; Schmitt, Anita

2016-09-01

Dendritic cells (DCs) are the most professional antigen-presenting cells eliciting cellular and humoral immune responses against cancer cells by expressing these antigens on MHC class I/II complexes to T cells. Therefore, they have been employed in many clinical trials as cancer vaccines for patients with cancer. This review focuses on the use of DCs in leukemia patients expressing leukemia-associated antigens (LAAs). The contribution of both stimulating vs. tolerogenic DCs as well as of other factors to the milieu of anti-leukemia immune responses are discussed. Several DC vaccination strategies like leukemia lysate, proteins and peptides have been developed. Next generation DC vaccines comprise transduction of DCs with retroviral vectors encoding for LAAs, cytokines and costimulatory molecules as well as transfection of DCs with naked RNA encoding for LAAs. Published as well as ongoing clinical trials are reported and critically reviewed. Future results will demonstrate whether next-generation DCs are really superior to conventional pulsing with peptide, protein or tumor lysate. However, currently available methods based on nucleic acid transfection/transduction are tempting in terms of material production costs and time for clinical application according to good manufacturing practice (GMP).

Knowledge of cervical cancer and HPV vaccine in Bangladeshi women: a population based, cross-sectional study.

Science.gov (United States)

Islam, Jessica Yasmine; Khatun, Fatema; Alam, Anadil; Sultana, Farhana; Bhuiyan, Afsana; Alam, Nazmul; Reichenbach, Laura; Marions, Lena; Rahman, Mustafizur; Nahar, Quamrun

2018-01-11

The objective of this study was to assess the level of knowledge of cervical cancer among Bangladeshi women and to assess their willingness to receive the human papillomavirus (HPV) vaccine. A population-based, cross-sectional survey was conducted from July to December 2011 in one urban and one rural area of Bangladesh. A total of 2037 ever-married women, aged 14 to 64 years, were interviewed using a structured questionnaire. Data on socio-demographic characteristics and knowledge of cervical cancer were collected. Willingness to receive the HPV vaccine was assessed. Univariate analyses were completed using quantitative data collected. Multivariable logistic regression models were developed to identify factors associated with having heard of cervical cancer and the HPV vaccine. The majority of study participants reported to have heard of cervical cancer (urban: 89.7%, rural 93.4%; P = 0.003). The odds of having heard of cervical cancer were significantly higher in urban women aged 35-44 years (aOR: 2.92 (1.34-6.33) and rural women aged 25-34 years (aOR: 2.90 (1.24-6.73) compared to those aged less than 24 years. Very few women reported to have detailed knowledge on risk factors (urban:9.1%, rural: 8.8%) and prevention (urban: 6.4%, rural: 4.4%) of cervical cancer. In our sample, one in five urban women and one in twenty rural women heard about a vaccine that can prevent cervical cancer. Among urban women, secondary education or higher (aOR: 3.48, 95% CI: 1.67-7.25), age of 20 years and above at marriage (aOR: 2.83, 95% CI: 1.61-5.00), and high socioeconomic status (aOR: 2.25, 95% CI: 1.28-3.95) were factors associated with having heard of the HPV vaccine. Willingness to receive the HPV vaccine among study participants either for themselves (urban: 93.9%, rural: 99.4%) or for their daughters (urban: 91.8%, rural: 99.2%) was high. Detailed knowledge of cervical cancer among Bangladeshi women was found to be poor. Education on cervical cancer must include

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.

Sustainable vaccine development: a vaccine manufacturer's perspective.

Science.gov (United States)

Rappuoli, Rino; Hanon, Emmanuel

2018-05-08

Vaccination remains the most cost-effective public health intervention after clean water, and the benefits impressively outweigh the costs. The efforts needed to fulfill the steadily growing demands for next-generation and novel vaccines designed for emerging pathogens and new indications are only realizable in a sustainable business model. Vaccine development can be fast-tracked through strengthening international collaborations, and the continuous innovation of technologies to accelerate their design, development, and manufacturing. However, these processes should be supported by a balanced project portfolio, and by managing sustainable vaccine procurement strategies for different types of markets. Collectively this will allow a gradual shift to a more streamlined and profitable vaccine production, which can significantly contribute to the worldwide effort to shape global health. Copyright © 2018 GlaxoSmithKine Biologicals SA. Published by Elsevier Ltd.. All rights reserved.

Human Papilloma Virus Vaccination for Control of Cervical Cancer ...

African Journals Online (AJOL)

Human Papilloma Virus Vaccination for Control of Cervical Cancer: A ... Primary HPV prevention may be the key to reducing incidence and burden of cervical cancer ... Other resources included locally-published articles and additional internet ...

InCVAX, a novel in situ autologous cancer vaccine (Conference Presentation)

Science.gov (United States)

Lam, Samuel Siu Kit; Chen, Wei R.

2017-02-01

Cancer immunotherapy is the concept of harnessing our own immune system to fight against cancer cells. The most attractive features of immunotherapy include relatively low toxicities compared to traditional therapies (surgery, chemotherapy and radiation), the possibility of eliminating distant metastases and the potential of preventing relapses. After decades of research, its therapeutic efficacy has finally been recognized and a number of approaches has been approved by the FDA over the past 10 years. Dendritic cell vaccine and checkpoint blockade strategies were among the first to enter the clinic, with many other strategies such as peptide vaccine, whole cell tumor vaccine, and adoptive T cell transfer (with Chimeric Antigen Receptors) etc. closely following in clinical trials. Immunophotonics is developing a novel in situ autologous cancer vaccine (InCVAX) by combining thermal laser phototherapy with immunotherapy. InCVAX is a two-step procedure: (1) Delivery of low-power thermal laser to any accessible tumor to cause partial cell death, increase tumor immunogenicity by releasing tumor antigens and Damage Associated Molecular Patterns (DAMPs). This is followed immediately by (2) injection of our proprietary immunostimulant, N-dihydro-acetylglucosamine (GC), into the laser-treated region to stimulate antigen presenting cells. These two steps work synergistically to enhance the systemic anti-tumor T cell response which is capable of eliminating both primary and metastatic cancers in some patients with advanced, stage III/IV, breast cancer with minimal toxicity. Our approach has the unique benefits of stimulating an immune response against a wide array of tumor antigens, and thus the potential to induce a strong, comprehensive and long-term anti-tumor protection in patients with minimal costs. Following early data showing efficacy in breast cancer patients, a multi-center, randomized clinical trial is currently underway in South America to consolidate the findings

Real-time PCR analysis of genes encoding tumor antigens in esophageal tumors and a cancer vaccine

NARCIS (Netherlands)

Weinert, Brian T.; Krishnadath, Kausilia K.; Milano, Francesca; Pedersen, Ayako W.; Claesson, Mogens H.; Zocca, Mai-Britt

2009-01-01

Tumor antigens are the primary target of therapeutic cancer vaccines. We set out to define and compare the expression pattern of tumor antigen genes in esophagus carcinoma biopsies and in an allogeneic tumor lysate-based cancer vaccine, MelCancerVac. Cells used for vaccine production were treated

Immune Suppression in Tumors as a Surmountable Obstacle to Clinical Efficacy of Cancer Vaccines

International Nuclear Information System (INIS)

Wieërs, Grégoire; Demotte, Nathalie; Godelaine, Danièle; Bruggen, Pierre van der

2011-01-01

Human tumors are usually not spontaneously eliminated by the immune system and therapeutic vaccination of cancer patients with defined antigens is followed by tumor regressions only in a small minority of the patients. The poor vaccination effectiveness could be explained by an immunosuppressive tumor microenvironment. Because T cells that infiltrate tumor metastases have an impaired ability to lyse target cells or to secrete cytokine, many researchers are trying to decipher the underlying immunosuppressive mechanisms. We will review these here, in particular those considered as potential therapeutic targets. A special attention will be given to galectins, a family of carbohydrate binding proteins. These lectins have often been implicated in inflammation and cancer and may be useful targets for the development of new anti-cancer therapies

Overview of Current Humman Papilloma Virus (HPV Vaccination

Directory of Open Access Journals (Sweden)

Cumhur Artuk

2013-06-01

Full Text Available Persistent viral infection with high-risk human papillomavirus (HPV genotypes causes virtually all cancer of the cervix. The same HPV genotypes (“types” also cause cases of anal cancer. Cervical cancer is the third most frequent cancer in women worldwide after breast and colorectal cancers. It ranks fourth of women’s cancers according to the mortality ratio. Two vaccines have been developed against HPV infection; one is a quadrivalent vaccine (Gardasil™ and the other is a bivalent vaccine (Cervarix™. This topic will cover issues related to HPV infections, routine HPV immunization recommendations, vaccination in special patient populations, the cost-effectiveness of HPV vaccination, and vaccine safety. [TAF Prev Med Bull 2013; 12(3.000: 327-334

Optimised electroporation mediated DNA vaccination for treatment of prostate cancer.

LENUS (Irish Health Repository)

Ahmad, Sarfraz

2010-01-01

ABSTRACT: BACKGROUND: Immunological therapies enhance the ability of the immune system to recognise and destroy cancer cells via selective killing mechanisms. DNA vaccines have potential to activate the immune system against specific antigens, with accompanying potent immunological adjuvant effects from unmethylated CpG motifs as on prokaryotic DNA. We investigated an electroporation driven plasmid DNA vaccination strategy in animal models for treatment of prostate cancer. METHODS: Plasmid expressing human PSA gene (phPSA) was delivered in vivo by intra-muscular electroporation, to induce effective anti-tumour immune responses against prostate antigen expressing tumours. Groups of male C57 BL\\/6 mice received intra-muscular injections of phPSA plasmid. For phPSA delivery, quadriceps muscle was injected with 50 mug plasmid. After 80 seconds, square-wave pulses were administered in sequence using a custom designed pulse generator and acustom-designed applicator with 2 needles placed through the skin central to the muscle. To determine an optimum treatment regimen, three different vaccination schedules were investigated. In a separate experiment, the immune potential of the phPSA vaccine was further enhanced with co- administration of synthetic CpG rich oligonucleotides. One week after last vaccination, the mice were challenged subcutaneously with TRAMPC1\\/hPSA (prostate cancer cell line stably expressing human PSA) and tumour growth was monitored. Serum from animals was examined by ELISA for anti-hPSA antibodies and for IFNgamma. Histological assessment of the tumours was also carried out. In vivo and in vitro cytotoxicity assays were performed with splenocytes from treated mice. RESULTS: The phPSA vaccine therapy significantly delayed the appearance of tumours and resulted in prolonged survival of the animals. Four-dose vaccination regimen provided optimal immunological effects. Co - administration of the synthetic CpG with phPSA increased anti-tumour responses

Vaccination efficacy with marrow mesenchymal stem cell against cancer was enhanced under simulated microgravity

International Nuclear Information System (INIS)

Li, Jing; Chen, Jun; Li, Xiuyu; Qian, Yanfang

2017-01-01

Stem cell vaccination can induce consistent and strong anti-tumor immunity against cancer in mice model. The antigenic similarity between tumors and embryos has been appreciated for many years and reflects the expression of embryonic gene products by cancer cells and/or cancer-initiating stem cells. Taking advantage of this similarity, we have tested a prophylactic lung cancer vaccine composed of allogeneic murine MSCs. Based on this conception, we first compared their tumor vaccines intervention effects of adult MSCs and MSCs under simulated microgravity (MSC/SMG). In this study, BALB/c mice were vaccinated with MSCs or MSC/SMG, compared with mice vaccinated with phosphate buffered saline (PBS) as negative controls. We then subcutaneously implanted the A549 human lung cancer cell line into vaccinated mice and monitored tumor growth potential in vivo. The smaller tumor size and less tumor weight were observed in mice vaccinated with MSCs or MSC/SMG, compared with that of the Control group. Particularly, it was much more significant in the group of MSC/SMG than that group of the MSCs. Vaccination with SMG treated MSCs inhibited proliferation and promoted apoptosis of tumor tissue. SMG/MSC vaccination induced bothTh1-mediated cytokine response; CD8-dependent cytotoxic response which reduced the proportion of Treg cells. Furthermore, SMG/MSC vaccination significantly increased MHC1 and HSPs proteins expression. In conclusion, we demonstrated the SMG could improve tumor-suppressive activity of MSC. The enhanced anti-tumor immune response of MSCs/SMG was strongly associated with the higher expression of MHC class I molecule on DCs, and the abundance of HSPs in the SMG treated MSCs may make antigens in the MSC more cross-presentable to the host DCs for generating protective antitumor activity. This study gains an insight into the mechanism of MSCs anti-tumor efficacy and gives a new strategy for cancer therapies in the future. - Highlights: • Vaccination with SMG

Knowledge and Intention to Participate in Cervical Cancer Screening after the Human Papillomavirus Vaccine

Science.gov (United States)

Price, Rebecca Anhang; Koshiol, Jill; Kobrin, Sarah; Tiro, Jasmin A.

2011-01-01

Background If women who receive the human papillomavirus (HPV) vaccine are unduly reassured about the cancer prevention benefits of vaccination, they may choose not to participate in screening, thereby increasing their risk for cervical cancer. This study assesses adult women’s knowledge of the need to continue cervical cancer screening after HPV vaccination, describes Pap test intentions of vaccinated young adult women, and evaluates whether knowledge and intentions differ across groups at greatest risk for cervical cancer. Methods Data were from the 2008 Health Information National Trends Survey (HINTS) and the 2008 National Health Interview Survey (NHIS), which initiated data collection approximately 18 months after the first FDA approval of an HPV vaccine. We calculated associations between independent variables and the outcomes using chi-square tests. Results Of 1,586 female HINTS respondents ages 18 through 74, 95.6% knew that HPV-vaccinated women should continue to receive Pap tests. This knowledge did not vary significantly by race/ethnicity, education, income, or healthcare access. Among 1,101 female NHIS respondents ages 18 to 26 who had ever received a Pap test, the proportion (12.7%; n = 139) who reported receipt of the HPV vaccine were more likely than those not vaccinated to plan to receive a Pap test within three years (98.1% vs. 92.5%, pknowledge and intention to participate in Pap testing after HPV vaccination. The vast majority of young adult women who received the HPV vaccine within its first two years on the market intend to participate in cervical cancer screening in the near future. Future studies are needed to examine whether those vaccinated in adolescence will become aware of, and adhere to, screening guidelines as they become eligible. PMID:21473953

Vietnamese American women’s beliefs and perceptions on cervical cancer, cervical cancer screening, and cancer prevention vaccines: A community-based participatory study

Directory of Open Access Journals (Sweden)

Connie Kim Yen Nguyen-Truong

2017-12-01

Full Text Available Cervical cancer remains commonly diagnosed in Vietnamese American women. Despite efforts to increase cervical cancer screening among Vietnamese American women, participation rates are persistently lower than the national goal. The objective of this study is to explore beliefs of Vietnamese American women about cervical cancer, cervical cancer screening, and cancer prevention vaccines. A qualitative descriptive investigation captured group perceptions about meaning and beliefs of cervical cancer, screening, and cancer prevention vaccines, and participants’ stories using a community-based participatory research approach. Forty Vietnamese American women were recruited from the Portland, Oregon metropolitan area into four focus groups. Using a process of directed content analysis, focus group transcripts were coded for themes. We found that cervical cancer continues to be a difficult topic to discuss, and Vietnamese American women may not bring the topic up themselves to their health care providers. Some women experienced intense emotions of fear or shame of having their cervix examined. Women delayed seeking cervical cancer screening and needed to have early warning signs, which guided them as to when to seek health care. Women focused on cleanliness through vaginal and/or perineal washing as primary prevention for cervical cancer. There were limited awareness and knowledge about cancer prevention vaccines, specifically the human papillomavirus. Some women relied heavily on their informal social networks of family, friends, or community for health knowledge. Fear and misunderstanding dominated the beliefs of Vietnamese American women about cervical cancer screening and prevention. These findings underscored the importance of having culturally-specific findings, which will inform a multicomponent intervention to promote cervical cancer screening and cancer prevention vaccine uptake within this population.

Knowledge, Perception, and Acceptance of HPV Vaccination and Screening for Cervical Cancer among Women in Yogyakarta

Science.gov (United States)

Endarti, Dwi; Satibi, Satibi; Kristina, Susi Ari; Farida, Muhaya Almira; Rahmawanti, Yuni; Andriani, Tika

2018-04-27

Objective: To determine knowledge, perception, and acceptance related to cervical cancer, HPV vaccination and screening for cervical cancer among Indonesian women, particularly in Yogyakarta province. Methods: A convenience sample of 392 women consists of 192 young women, 100 mothers of girls aged 12 – 15 years, and 100 adult women in Yogyakarta province, Indonesia was participated in this study. A self-administered paper-based questionnaire was used to determine demographics characteristics of respondents, as well as their knowledge – perception – acceptance related to cervical cancer, HPV vaccination, and screening for cervical cancer. Data collection were conducted during December 2013 to March 2014. Descriptive statistics was used to analyze description of demographics characteristics, knowledge, perception, and acceptance; while crosstab analysis using Chi-Square was used to analyze the relationship between demographics characteristics versus knowledge, perception, and acceptance. Results: This study found that knowledge and perception regarding cervical cancer, HPV vaccination, and screening for cervical cancer among women in Indonesia, particularly in Yogyakarta Province were still insufficient, however the acceptance was good. Among female young women, 64% had good knowledge, 62% had positive perception of cervical cancer and HPV vaccination, and 92% tended to accept HPV vaccination. Among mothers of girls aged 12 – 15 years, 44% had good knowledge, 46% had positive perception of cervical cancer and HPV vaccination, and 91% tended to accept HPV vaccination for their daughters. Among adult women, 68% had good knowledge, 57% had positive perception of cervical cancer and screening for cervical cancer, and 90% tended to accept cervical cancer screening. In general, demographics characteristics of having experience and exposure to information had significant relationship with knowledge, perception, and acceptance of HPV vaccination and screening for

[Vaccine against human papilloma virus].

Science.gov (United States)

Juárez-Albarrán, Alfredo César; Juárez-Gámez, Carlos Alberto

2008-01-01

Genital human papilloma virus infection (HPV) is the most common sexually transmitted infection worldwide, it is the cause of genital warts, and it is related with cervical cancer, the second most common cause of death from cancer in women in America, and the first in underdeveloped countries, and it is related with penis and prostate cancer in males also, and with anal cancer in both genders. This review examines the most important actual facts about HPV infection, and the new prophylactic vaccines. Two versions of the vaccine had been developed, both target HPV 16 and HPV 18, which involve approximately 70% of cervical cancer. One of them also targets HPV 6 and HPV 11, which account for approximately 90% of external genital warts. Both vaccines have an excellent safety profile, are highly immunogenic, and have atributed complete type specific protection against persistent infection and associated lesions in fully vaccinated girls and young women. The role of men as carriers of HPV as well as vectors for transmission is well documented. Several clinical trials are currently under way to determine the efficacy of vaccinating men. Reducing the cost of vaccination would be a priority for the developing world in order to get a broad target in poor countries.

A novel cancer vaccine strategy based on HLA-A*0201 matched allogeneic plasmacytoid dendritic cells.

Directory of Open Access Journals (Sweden)

Caroline Aspord

Full Text Available BACKGROUND: The development of effective cancer vaccines still remains a challenge. Despite the crucial role of plasmacytoid dendritic cells (pDCs in anti-tumor responses, their therapeutic potential has not yet been worked out. We explored the relevance of HLA-A*0201 matched allogeneic pDCs as vectors for immunotherapy. METHODS AND FINDINGS: Stimulation of PBMC from HLA-A*0201(+ donors by HLA-A*0201 matched allogeneic pDCs pulsed with tumor-derived peptides triggered high levels of antigen-specific and functional cytotoxic T cell responses (up to 98% tetramer(+ CD8 T cells. The pDC vaccine demonstrated strong anti-tumor therapeutic in vivo efficacy as shown by the inhibition of tumor growth in a humanized mouse model. It also elicited highly functional tumor-specific T cells ex-vivo from PBMC and TIL of stage I-IV melanoma patients. Responses against MelA, GP100, tyrosinase and MAGE-3 antigens reached tetramer levels up to 62%, 24%, 85% and 4.3% respectively. pDC vaccine-primed T cells specifically killed patients' own autologous melanoma tumor cells. This semi-allogeneic pDC vaccine was more effective than conventional myeloid DC-based vaccines. Furthermore, the pDC vaccine design endows it with a strong potential for clinical application in cancer treatment. CONCLUSIONS: These findings highlight HLA-A*0201 matched allogeneic pDCs as potent inducers of tumor immunity and provide a promising immunotherapeutic strategy to fight cancer.

Midwives at youth clinics attitude to HPV vaccination and their role in cervical cancer prevention.

Science.gov (United States)

Oscarsson, Marie G; Dahlberg, Annica; Tydén, Tanja

2011-11-01

To explore youth clinic midwives role in cervical cancer prevention and their attitude to HPV vaccination. Individual interviews with 13 midwives working at youth clinics in Sweden. The interviews were recorded, transcribed, and analysed by qualitative content analysis. Three themes were identified in the qualitative content analysis: "Cervical cancer prevention not a prioritised area", "Ambivalence to the HPV vaccine", and "Gender and socioeconomic controversies". Few midwives talked spontaneously about cervical cancer prevention. The responsibility for providing information about HPV vaccination was considered as primarily that of school health nurses and parents. Midwives were positive about the HPV vaccination, but recognised certain risks, such as its potential negative impact on cervical cancer screening and increased sexual risk taking. The midwives expressed concerns with medical risks, such as side effects and unknown long-term effects of the HPV vaccine. The midwives in the study had ethical concerns that boys were not included in the program and not all families had the financial resources to vaccinate their children. Thus, weak socioeconomic groups might be excluded. The midwives considered cervical cancer prevention as important, but did not integrate information on the HPV vaccine into their routine work, mainly because young people visiting youth clinics had had their sexual debut and they were concerned about the medical risks and that the vaccine was too expensive. Copyright © 2011 Elsevier B.V. All rights reserved.

Genetically modified dendritic cell-based cancer vaccines

Czech Academy of Sciences Publication Activity Database

Bubeník, Jan

2001-01-01

Roč. 47, č. 5 (2001), s. 153-155 ISSN 0015-5500 R&D Projects: GA MZd NC5526 Keywords : dendritic cell s * cancer vaccines Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.519, year: 2001

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.

Cancer patients treated with sunitinib or sorafenib have sufficient antibody and cellular immune responses to warrant influenza vaccination.

Science.gov (United States)

Mulder, Sasja F; Jacobs, Joannes F M; Olde Nordkamp, Michel A M; Galama, Joep M D; Desar, Ingrid M E; Torensma, Ruurd; Teerenstra, Steven; Mulders, Peter F A; Vissers, Kris C P; Punt, Cornelis J A; de Vries, I Jolanda M; van Herpen, Carla M L

2011-07-01

The tyrosine kinase inhibitors sorafenib and sunitinib have efficacy in several types of cancer. Recent studies indicate that these agents affect the immune system. The way it affects the immune response to influenza vaccination is unknown. The aim of this study was to elucidate the specific immune response to seasonal flu vaccination in cancer patients treated with sunitinib or sorafenib. Sunitinib- or sorafenib-treated cancer patients were vaccinated against seasonal influenza with an inactivated vaccine. Healthy controls and patients with metastatic renal cell cancer (mRCC) without systemic treatment (nontreated mRCC controls) were included for comparison. Antibody responses were measured at baseline, day 8, and day 22 by a standard hemagglutination inhibition assay and cellular T-cell responses at baseline and day 8 by proliferation assay and secretion of cytokines. Forty subjects were enrolled: 16 patients treated with sunitinib, 6 patients with sorafenib, 7 nontreated mRCC controls, and 11 healthy controls. All patients treated with sunitinib and sorafenib developed seroprotection rates comparable with controls. Functional T-cell reactivity was observed in all groups, except for patients treated with sorafenib who showed a decreased proliferation rate and IFN-γ/IL-2 production and increased IL-10 compared with healthy controls. We conclude that influenza vaccination should be recommended to cancer patients treated with sunitinib or sorafenib.

Dendritic Cell-Based Adjuvant Vaccination Targeting Wilms’ Tumor 1 in Patients with Advanced Colorectal Cancer

Directory of Open Access Journals (Sweden)

Shigetaka Shimodaira

2015-12-01

Full Text Available Despite significant recent advances in the development of immune checkpoint inhibitors, the treatment of advanced colorectal cancer involving metastasis to distant organs remains challenging. We conducted a phase I study to investigate the safety and immunogenicity of Wilms’ tumor (WT1 class I/II peptides-pulsed dendritic cell DC vaccination for patients with advanced colorectal cancer. Standard treatment comprising surgical resection and chemotherapy was followed by one course of seven biweekly administrations of 1–2 × 107 DCs with 1–2 KE of OK-432 (streptococcal preparation in three patients. Clinical efficacy was confirmed based on WT1 expression using immunohistochemistry on paraffin-embedded tissues and immune monitoring using tetramer analysis and enzyme-linked immunosorbent spot (ELISPOT assays. WT1 expression with human leukocyte antigen (HLA-class I molecules was detected in surgical resected tissues. Adverse reactions to DC vaccinations were tolerable under an adjuvant setting. WT1-specific cytotoxic T cells were detected by both modified WT1-peptide/HLA-A*24:02 tetramer analysis and/or interferon-γ-producing cells through the use of ELISPOT assays after the first DC vaccination. Immunity acquired from DC vaccination persisted for two years with prolonged disease-free and overall survival. The present study indicated that DC vaccination targeting WT1 demonstrated the safety and immunogenicity as an adjuvant therapy in patients with resectable advanced colorectal cancer.

Burden of disease associated with cervical cancer in malaysia and potential costs and consequences of HPV vaccination.

Science.gov (United States)

Aljunid, S; Zafar, A; Saperi, S; Amrizal, M

2010-01-01

An estimated 70% of cervical cancers worldwide are attributable to persistent infection with human papillomaviruses (HPV) 16 and 18. Vaccination against HPV 16/18 has been shown to dramatically reduce the incidence of associated precancerous and cancerous lesions. The aims of the present analyses were, firstly, to estimate the clinical and economic burden of disease attributable to HPV in Malaysia and secondly, to estimate long-term outcomes associated with HPV vaccination using a prevalence-based modeling approach. In the first part of the analysis costs attributable to cervical cancer and precancerous lesions were estimated; epidemiologic data were sourced from the WHO GLOBOCAN database and Malaysian national data sources. In the second part, a prevalence-based model was used to estimate the potential annual number of cases of cervical cancer and precancerous lesions that could be prevented and subsequent HPV-related treatment costs averted with the bivalent (HPV 16/18) and the quadrivalent (HPV 16/18/6/11) vaccines, at the population level, at steady state. A vaccine efficacy of 98% was assumed against HPV types included in both vaccines. Effectiveness against other oncogenic HPV types was based on the latest results from each vaccine's respective clinical trials. In Malaysia there are an estimated 4,696 prevalent cases of cervical cancer annually and 1,372 prevalent cases of precancerous lesions, which are associated with a total direct cost of RM 39.2 million with a further RM 12.4 million in indirect costs owing to lost productivity. At steady state, vaccination with the bivalent vaccine was estimated to prevent 4,199 cervical cancer cases per year versus 3,804 cases for the quadrivalent vaccine. Vaccination with the quadrivalent vaccine was projected to prevent 1,721 cases of genital warts annually, whereas the annual number of cases remained unchanged with the bivalent vaccine. Furthermore, vaccination with the bivalent vaccine was estimated to avert RM 45

Changes in cytokine and biomarker blood levels in patients with colorectal cancer during dendritic cell-based vaccination

DEFF Research Database (Denmark)

Burgdorf, Stefan; Claesson, Mogens; Nielsen, Hans

2009-01-01

Introduction. Immunotherapy based on dendritic cell vaccination has exciting perspectives for treatment of cancer. In order to clarify immunological mechanisms during vaccination it is essential with intensive monitoring of the responses. This may lead to optimization of treatment and prediction......-inflammatory cytokines in serum of patients who achieved stable disease following vaccination suggest the occurrence of vaccine-induced Th1 responses. Since Th1 responses seem to be essential in cancer immunotherapy this may indicate a therapeutic potential of the vaccine....... of responding patients. The aim of this study was to evaluate cytokine and biomarker responses in patients with colorectal cancer treated with a cancer vaccine based on dendritic cells pulsed with an allogeneic melanoma cell lysate. Material and methods. Plasma and serum samples were collected prior...

Liposome-based synthetic long peptide vaccines for cancer immunotherapy

NARCIS (Netherlands)

Varypataki, E.M.

2016-01-01

Synthetic long peptides (SLP) derived from cancer-associated antigens hold great promise as well-defined antigens for cancer immunotherapy. Clinical studies showed that SLP vaccines have functional potency when applied to pre-malignant stage patients, but need to be improved for use as a therapeutic

Immunological and antitumor effects of IL-23 as a cancer vaccine adjuvant

NARCIS (Netherlands)

Overwijk, Willem W.; de Visser, Karin E.; Tirion, Felicia H.; de Jong, Laurina A.; Pols, Thijs W. H.; van der Velden, Yme U.; van den Boorn, Jasper G.; Keller, Anna M.; Buurman, Wim A.; Theoret, Marc R.; Blom, Bianca; Restifo, Nicholas P.; Kruisbeek, Ada M.; Kastelein, Robert A.; Haanen, John B. A. G.

2006-01-01

The promising, but modest, clinical results of many human cancer vaccines indicate a need for vaccine adjuvants that can increase both the quantity and the quality of vaccine-induced, tumor-specific T cells. In this study we tested the immunological and antitumor effects of the proinflammatory

Vaccination with Necroptotic Cancer Cells Induces Efficient Anti-tumor Immunity

Directory of Open Access Journals (Sweden)

Tania Løve Aaes

2016-04-01

Full Text Available Successful immunogenic apoptosis in experimental cancer therapy depends on the induction of strong host anti-tumor responses. Given that tumors are often resistant to apoptosis, it is important to identify alternative molecular mechanisms that elicit immunogenic cell death. We have developed a genetic model in which direct dimerization of FADD combined with inducible expression of RIPK3 promotes necroptosis. We report that necroptotic cancer cells release damage-associated molecular patterns and promote maturation of dendritic cells, the cross-priming of cytotoxic T cells, and the production of IFN-γ in response to tumor antigen stimulation. Using both FADD-dependent and FADD-independent RIPK3 induction systems, we demonstrate the efficient vaccination potential of immunogenic necroptotic cells. Our study broadens the current concept of immunogenic cell death and opens doors for the development of new strategies in cancer therapy.

Differential Adverse Event Profiles Associated with BCG as a Preventive Tuberculosis Vaccine or Therapeutic Bladder Cancer Vaccine Identified by Comparative Ontology-Based VAERS and Literature Meta-Analysis.

Directory of Open Access Journals (Sweden)

Jiangan Xie

Full Text Available M. bovis strain Bacillus Calmette-Guérin (BCG has been the only licensed live attenuated vaccine against tuberculosis (TB for nearly one century and has also been approved as a therapeutic vaccine for bladder cancer treatment since 1990. During its long time usage, different adverse events (AEs have been reported. However, the AEs associated with the BCG preventive TB vaccine and therapeutic cancer vaccine have not been systematically compared. In this study, we systematically collected various BCG AE data mined from the US VAERS database and PubMed literature reports, identified statistically significant BCG-associated AEs, and ontologically classified and compared these AEs related to these two types of BCG vaccine. From 397 VAERS BCG AE case reports, we identified 64 AEs statistically significantly associated with the BCG TB vaccine and 14 AEs with the BCG cancer vaccine. Our meta-analysis of 41 peer-reviewed journal reports identified 48 AEs associated with the BCG TB vaccine and 43 AEs associated with the BCG cancer vaccine. Among all identified AEs from VAERS and literature reports, 25 AEs belong to serious AEs. The Ontology of Adverse Events (OAE-based ontological hierarchical analysis indicated that the AEs associated with the BCG TB vaccine were enriched in immune system (e.g., lymphadenopathy and lymphadenitis, skin (e.g., skin ulceration and cyanosis, and respiratory system (e.g., cough and pneumonia; in contrast, the AEs associated with the BCG cancer vaccine mainly occurred in the urinary system (e.g., dysuria, pollakiuria, and hematuria. With these distinct AE profiles detected, this study also discovered three AEs (i.e., chills, pneumonia, and C-reactive protein increased shared by the BCG TB vaccine and bladder cancer vaccine. Furthermore, our deep investigation of 24 BCG-associated death cases from VAERS identified the important effects of age, vaccine co-administration, and immunosuppressive status on the final BCG

Knowledge and Awareness about Cervical Cancer Vaccine (HPV) Among Parents in Sharjah

Science.gov (United States)

Saqer, Ahmad; Ghazal, Shaymaa; Barqawi, Hiba; Babi, Juman Adnan; AlKhafaji, Ranya; Elmekresh, Mohamed Mohsen

2017-05-01

Background and aim: Cervical cancer (CC) is the 7th most common cancer worldwide. It is the 4th most common cancer in females causing 7.5% of all female cancer deaths. Human Papilloma Virus (HPV) infection is the leading cause of CC and other diseases worldwide. Despite several measures taken to reduce the risk of infection with HPV, the most effective method remains the HPV vaccine. The aim of this study was to assess the knowledge and attitudes of parents in Sharjah towards HPV and whether or not they would vaccinate their daughters. Methods and Material: A quantitative, observational cross-sectional study of 400 subjects was conducted in public venues in Sharjah. Probability sampling method was used for selection of subjects (parents who have daughters). A self-administered 32- question questionnaire was distributed. SPSS 21 (Statistical Package for Social Sciences) was used for entry and analysis of data. Frequency was calculated, Chi square test was used to conduct bivariate analysis and bar charts and tables were used to present the results. Results: 78.3% of the population had heard of CC, 41.3 % of HPV, and 36.5% of the HPV vaccine. Among them, the percentages of the correctly answered knowledge-related questions were found to be 66.2%, 50.9% and 52.1% for CC, HPV and HPV vaccine, respectively. 76.6% of parents were willing to vaccinate their daughters. The percentage increased to 92.9%, if the ministry of health (MOH) recommended the vaccine. A significant correlation was found between the spouse’s level of education, HPV (Pearson-chi square value: 5.049 and p: 0.025) and HPV vaccine (Pearson-chi square value: 4.057 and p:0.044). Conclusions: Despite the public’s lack of knowledge, the study showed a noticeable increase in parent’s willingness to vaccinate their daughters if the government recommends and provides the HPV vaccine. However, proper evaluation of the vaccine’s efficacy from a socioeconomic point of view is needed before recommending

Knowledge level of working and student nurses on cervical cancer and human papilloma virus vaccines.

Science.gov (United States)

Topan, Aysel; Ozturk, Ozlem; Eroglu, Hulya; Bahadir, Ozgur; Harma, Muge; Harma, Mehmet Ibrahim

2015-01-01

To determine knowledge levels of working and student nurses about cervical cancer and prophylactic cancer vaccines. This study was performed on 259 nursing students in the Department of Nursing and 137 nurses working in Health Research and Practice Center, approved to participate in the study between April-June 2012. The study was performed universally without selecting a sample. A questionnaire that was prepared for evaluating participants' knowledge and attitudes about human papilloma virus (HPV) vaccine was distributed to the nurses and data obtained from the forms were transferred to SPSS 15.00 program and statistically analyzed. It was found that 54.8% of the student nurses were between 21-24 years old and 13.1% of working students were between 25-28 years old. When student nurses and working nurses were compared in terms of their knowledge about the causes of cervical cancer, their ideas about prevention from cervical cancer with HPV vaccine, their ideas about possible risks of HPV vaccine and conservation ratios of HPV vaccine, it was observed that there were no statistically significant differences (p>0.05). When student nurses and working nurses were compared in terms of the information-source about HPV, ways of HPV contamination, awareness about people who are susceptible to HPV contamination and age of HPV vaccination, it was determined that there was a statistically significant difference (pknowledge about cervical cancer and HPV vaccine, but this was not sufficient. Therefore; it is recommended to use verbal, written and visual communication tools intensively in order to have topics on cervical cancer, early diagnosis and prevention in bachelor and master programs for nurses, to inform society about cervical cancer and HPV vaccine for public health and to teach precautions for its prevention.

Real-time PCR analysis of genes encoding tumor antigens in esophageal tumors and a cancer vaccine

DEFF Research Database (Denmark)

Weinert, Brian T; Krishnadath, Kausilia K; Milano, Francesca

2009-01-01

Tumor antigens are the primary target of therapeutic cancer vaccines. We set out to define and compare the expression pattern of tumor antigen genes in esophagus carcinoma biopsies and in an allogeneic tumor lysate-based cancer vaccine, MelCancerVac. Cells used for vaccine production were treated...... in the production of the vaccine. Quantitative PCR was used to assay 74 tumor antigen genes in patients with squamous cell carcinoma of the esophagus. 81% (13/16) of tumors expressed more than five cancer/testis (CT) antigens. A total of 96 genes were assayed in the tumor cell clone (DDM1.7) used to make tumor cell...

Poxvirus-based vaccine therapy for patients with advanced pancreatic cancer

Directory of Open Access Journals (Sweden)

Seo Kang

2007-11-01

Full Text Available Abstract Purpose An open-label Phase 1 study of recombinant prime-boost poxviruses targeting CEA and MUC-1 in patients with advanced pancreatic cancer was conducted to determine safety, tolerability and obtain preliminary data on immune response and survival. Patients and methods Ten patients with advanced pancreatic cancer were treated on a Phase I clinical trial. The vaccination regimen consisted of vaccinia virus expressing tumor antigens carcinoembryonic antigen (CEA and mucin-1 (MUC-1 with three costimulatory molecules B7.1, ICAM-1 and LFA-3 (TRICOM (PANVAC-V and fowlpox virus expressing the same antigens and costimulatory molecules (PANVAC-F. Patients were primed with PANVAC-V followed by three booster vaccinations using PANVAC-F. Granulocyte-macrophage colony-stimulating factor (GM-CSF was used as a local adjuvant after each vaccination and for 3 consecutive days thereafter. Monthly booster vaccinations for up to 12 months were provided for patients without progressive disease. Peripheral blood was collected before, during and after vaccinations for immune analysis. Results The most common treatment-related adverse events were mild injection-site reactions. Antibody responses against vaccinia virus was observed in all 10 patients and antigen-specific T cell responses were observed in 5 out of 8 evaluable patients (62.5%. Median overall survival was 6.3 months and a significant increase in overall survival was noted in patients who generated anti CEA- and/or MUC-1-specific immune responses compared with those who did not (15.1 vs 3.9 months, respectively; P = .002. Conclusion Poxvirus vaccination is safe, well tolerated, and capable of generating antigen-specific immune responses in patients with advanced pancreatic cancer.

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.

Cost-effectiveness of HPV vaccination in the context of high cervical cancer incidence and low screening coverage.

Science.gov (United States)

Võrno, Triin; Lutsar, Katrin; Uusküla, Anneli; Padrik, Lee; Raud, Terje; Reile, Rainer; Nahkur, Oliver; Kiivet, Raul-Allan

2017-11-01

Estonia has high cervical cancer incidence and low screening coverage. We modelled the impact of population-based bivalent, quadrivalent or nonavalent HPV vaccination alongside cervical cancer screening. A Markov cohort model of the natural history of HPV infection was used to assess the cost-effectiveness of vaccinating a cohort of 12-year-old girls with bivalent, quadrivalent or nonavalent vaccine in two doses in a national, school-based vaccination programme. The model followed the natural progression of HPV infection into subsequent genital warts (GW); premalignant lesions (CIN1-3); cervical, oropharyngeal, vulvar, vaginal and anal cancer. Vaccine coverage was assumed to be 70%. A time horizon of 88years (up to 100years of age) was used to capture all lifetime vaccination costs and benefits. Costs and utilities were discounted using an annual discount rate of 5%. Vaccination of 12-year-old girls alongside screening compared to screening alone had an incremental cost-effectiveness ratio (ICER) of €14,007 (bivalent), €14,067 (quadrivalent) and €11,633 (nonavalent) per quality-adjusted life-year (QALY) in the base-case scenario and ranged between €5367-21,711, €5142-21,800 and €4563-18,142, respectively, in sensitivity analysis. The results were most sensitive to changes in discount rate, vaccination regimen, vaccine prices and cervical cancer screening coverage. Vaccination of 12-year-old girls alongside current cervical cancer screening can be considered a cost-effective intervention in Estonia. Adding HPV vaccination to the national immunisation schedule is expected to prevent a considerable number of HPV infections, genital warts, premalignant lesions, HPV related cancers and deaths. Although in our model ICERs varied slightly depending on the vaccine used, they generally fell within the same range. Cost-effectiveness of HPV vaccination was found to be most dependent on vaccine cost and duration of vaccine immunity, but not on the type of vaccine

Polymeric nanoparticles for co-delivery of synthetic long peptide antigen and poly IC as therapeutic cancer vaccine formulation

NARCIS (Netherlands)

Rahimian, Sima; Fransen, Marieke F.; Kleinovink, Jan Willem; Christensen, Jonatan Riis; Amidi, Maryam|info:eu-repo/dai/nl/304834912; Hennink, Wim E.|info:eu-repo/dai/nl/070880409; Ossendorp, Ferry

2015-01-01

The aim of the current study was to develop a cancer vaccine formulation for treatment of human papillomavirus (HPV)-induced malignancies. Synthetic long peptides (SLPs) derived from HPV16 E6 and E7 oncoproteins have been used for therapeutic vaccination in clinical trials with promising results. In

Cancer Registries and Monitoring the Impact of Prophylactic Human Papillomavirus Vaccines: The Potential Role

OpenAIRE

Saraiya, Mona; Goodman, Marc T.; Datta, S. Deblina; Chen, Vivien W.; Wingo, Phyllis A.

2008-01-01

The recent US Food and Drug Administration licensure of a prophylactic vaccine against oncogenic human papillomavirus (HPV) types 16 and 18, the first of its kind, poses unique challenges in postmarketing vaccine surveillance, especially in measuring vaccine effectiveness against biologic endpoints of HPV infection. Historically, the national system of population-based cancer registries in the US has provided high-quality data on cancer incidence and mortality for the most important biologic ...

Effective cancer vaccine platform based on attenuated salmonella and a type III secretion system.

Science.gov (United States)

Xu, Xin; Hegazy, Wael A H; Guo, Linjie; Gao, Xiuhua; Courtney, Amy N; Kurbanov, Suhrab; Liu, Daofeng; Tian, Gengwen; Manuel, Edwin R; Diamond, Don J; Hensel, Michael; Metelitsa, Leonid S

2014-11-01

Vaccines explored for cancer therapy have been based generally on injectable vector systems used to control foreign infectious pathogens, to which the immune system evolved to respond naturally. However, these vectors may not be effective at presenting tumor-associated antigens (TAA) to the immune system in a manner that is sufficient to engender antitumor responses. We addressed this issue with a novel orally administered Salmonella-based vector that exploits a type III secretion system to deliver selected TAA in the cytosol of professional antigen-presenting cells in situ. A systematic comparison of candidate genes from the Salmonella Pathogenicity Island 2 (SPI2) locus was conducted in the vaccine design, using model antigens and a codon-optimized form of the human TAA survivin (coSVN), an oncoprotein that is overexpressed in most human cancers. In a screen of 20 SPI2 promoter:effector combinations, a PsifB::sseJ combination exhibited maximal potency for antigen translocation into the APC cytosol, presentation to CD8 T cells, and murine immunogenicity. In the CT26 mouse model of colon carcinoma, therapeutic vaccination with a lead PsifB::sseJ-coSVN construct (p8032) produced CXCR3-dependent infiltration of tumors by CD8 T cells, reversed the CD8:Treg ratio at the tumor site, and triggered potent antitumor activity. Vaccine immunogenicity and antitumor potency were enhanced by coadministration of the natural killer T-cell ligand 7DW8-5, which heightened the production of IL12 and IFNγ. Furthermore, combined treatment with p8032 and 7DW8-5 resulted in complete tumor regression in A20 lymphoma-bearing mice, where protective memory was demonstrated. Taken together, our results demonstrate how antigen delivery using an oral Salmonella vector can provide an effective platform for the development of cancer vaccines. ©2014 American Association for Cancer Research.

Burden of HPV-caused cancers in Denmark and the potential effect of HPV-vaccination

DEFF Research Database (Denmark)

Skorstengaard, Malene; Thamsborg, Lise Holst; Lynge, Elsebeth

2017-01-01

-caused cancers in women and men, and to evaluate the potential of HPV-vaccination in cancer control. Methods: Data were retrieved from the literature on population prevalence of high risk (HR) HPV, on HR HPV-prevalence and genotypes in HPV-related cancers, and on number of cytology samples in cervical screening...... were preventable with HPV vaccination. However, including screening prevented cervical cancers, the burden of cancers caused by HPV-infection would be 1300–2000 in women as compared to 234 in men. Conclusion: Taking screening prevented cervical cancers into account, the cancer control potential of HPV...

HPV vaccine awareness and the association of trust in cancer information from physicians among males.

Science.gov (United States)

Cooper, Dexter L; Hernandez, Natalie D; Rollins, Latrice; Akintobi, Tabia Henry; McAllister, Calvin

2017-05-09

Black and Hispanic men are diagnosed with more HPV-related cancers and at later stages compared to other racial/ethnic groups. Physician communication with men about HPV vaccination may be beneficial to increasing HPV vaccinations and decreasing HPV transmission. The purpose of this study was to examine HPV and HPV vaccine awareness among men by race, and the association between trust in cancer information from physicians and ever hearing about HPV and the HPV vaccine. U.S. adult males (age 18+) were identified from the 2014 Health Information National Trends Survey (HINTS) (n=1203). Binomial logistic regression models assessed the influences of race/ethnicity and trust of cancer information from physicians on men having heard of HPV and the HPV vaccination. Approximately 50% of the sample had never heard of HPV and 53% had never heard of the vaccine. Black men were less likely to know that HPV is sexually transmitted compared to White and Hispanic men (pcancer information compared to White and Black men (pawareness about HPV among men. Furthermore, statistically significant racial/ethnic differences were found in HPV vaccine knowledge and trust in receiving cancer information from physicians. Future interventions should include community-based approaches and improved physicians' HPV-related communication to increase knowledge and uptake of the HPV vaccine. Copyright © 2017 Elsevier Ltd. All rights reserved.

RhoC a new target for therapeutic vaccination against metastatic cancer

DEFF Research Database (Denmark)

Wenandy, L.; Sorensen, R.B.; Straten, P.T.

2008-01-01

Most cancer deaths are due to the development of metastases. Increased expression of RhoC is linked to enhanced metastatic potential in multiple cancers. Consequently, the RhoC protein is an attractive target for drug design. The clinical application of immunotherapy against cancer is rapidly...... of cancer makes RhoC a very attractive target for anti-cancer immunotherapy. Herein, we describe an HLA-A3 restricted epitope from RhoC, which is recognized by cytotoxic T cells. Moreover, RhoC-specific T cells show cytotoxic potential against HLA-matched cancer cells of different origin. Thus, RhoC may...... moving forward in multiple areas, including the adoptive transfer of anti-tumor-reactive T cells and the use of "therapeutic" vaccines. The over-expression of RhoC in cancer and the fact that immune escape by down regulation or loss of expression of this protein would reduce the morbidity and mortality...

A rationally designed combined treatment with an alphavirus-based cancer vaccine, sunitinib and low-dose tumor irradiation completely blocks tumor development

NARCIS (Netherlands)

Draghiciu, Oana; Boerma, Annemarie; Hoogeboom, Baukje Nynke; Nijman, Hans W.; Daemen, Toos

2015-01-01

The clinical efficacy of therapeutic cancer vaccines remains limited. For effective immunotherapeutic responses in cancer patients, multimodal approaches capable of both inducing antitumor immune responses and bypassing tumor-mediated immune escape seem essential. Here, we report on a combination

Perspectives for Preventive and Therapeutic HPV Vaccines

Science.gov (United States)

Lin, Ken; Doolan, Kimberley; Hung, Chien-Fu; Wu, T-C

2010-01-01

Cervical cancer is the second most common cause of female cancer death worldwide. Persistent infection with `high risk' HPV genotypes is the major etiological factor in cervical cancer and thus effective vaccination against HPV provides an opportunity to reduce the morbidity and mortality associated with HPV. The FDA has approved two preventive vaccines to limit the spread of HPV. However, these are unlikely to impact upon HPV prevalence and cervical cancer rates for many years. Furthermore, preventive vaccines do not exert therapeutic effects on pre-existing HPV infections and HPV-associated lesions. In order to further impact upon the burden of HPV infections worldwide, therapeutic vaccines are being developed. These vaccines aim to generate a cell-mediated immune response to infected cells. This review discusses current preventive and therapeutic HPV vaccines and their future directions. PMID:20123582

Cervical cancer and HPV: Awareness and vaccine acceptability among parents in Morocco.

Science.gov (United States)

Mouallif, Mustapha; Bowyer, Harriet L; Festali, Soukaina; Albert, Adelin; Filali-Zegzouti, Younes; Guenin, Samuel; Delvenne, Philippe; Waller, Jo; Ennaji, Moulay Mustapha

2014-01-09

Cervical cancer is a major public health concern in Morocco where it represents the second most common and lethal cancer in women. Human papillomavirus (HPV) vaccines have been licensed in Morocco since 2008 but there are no available data on their acceptability. This study aimed to assess awareness of HPV and the vaccine, and to identify factors associated with acceptability of the vaccine among parents in Morocco. We carried out a questionnaire-based survey using face-to-face interviews in a sample of 852 parents (670 mothers and 182 fathers) with at least one unmarried daughter ≤26 years. We collected data within public and private health centres and clinics in four regions in Morocco between July and August 2012. The main outcome measure was parental acceptability of the HPV vaccine for their daughter(s). Responses revealed very low awareness of HPV infection (4.7%) and the HPV vaccine (14.3%). None of the participants had vaccinated their daughter(s) against HPV and vaccine acceptability was low among mothers (32%) and fathers (45%). Higher education and income, previous awareness of the HPV vaccine and endorsement of the belief that a recommendation from the Ministry of Health or a doctor to have the vaccine would be encouraging, were associated with mothers' HPV vaccine acceptability. Non-acceptability among mothers was associated with having more than two daughters, believing the vaccine was expensive, lack of information and believing that whatever happens to an individual's health is God's will. The only factor associated with the fathers' acceptability of the vaccine was the cost of the vaccine. Increasing HPV and HPV vaccine awareness through educational campaigns, along with active recommendation by physicians and a publically funded vaccination programme could increase parental acceptability of the HPV vaccine in Morocco. Copyright © 2013 Elsevier Ltd. All rights reserved.

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

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.

Exploration of graphene oxide as an intelligent platform for cancer vaccines

Science.gov (United States)

Yue, Hua; Wei, Wei; Gu, Zonglin; Ni, Dezhi; Luo, Nana; Yang, Zaixing; Zhao, Lin; Garate, Jose Antonio; Zhou, Ruhong; Su, Zhiguo; Ma, Guanghui

2015-11-01

We explored an intelligent vaccine system via facile approaches using both experimental and theoretical techniques based on the two-dimensional graphene oxide (GO). Without extra addition of bio/chemical stimulators, the microsized GO imparted various immune activation tactics to improve the antigen immunogenicity. A high antigen adsorption was acquired, and the mechanism was revealed to be a combination of electrostatic, hydrophobic, and π-π stacking interactions. The ``folding GO'' acted as a cytokine self-producer and antigen reservoir and showed a particular autophagy, which efficiently promoted the activation of antigen presenting cells (APCs) and subsequent antigen cross-presentation. Such a ``One but All'' modality thus induced a high level of anti-tumor responses in a programmable way and resulted in efficient tumor regression in vivo. This work may shed light on the potential use of a new dimensional nano-platform in the development of high-performance cancer vaccines.We explored an intelligent vaccine system via facile approaches using both experimental and theoretical techniques based on the two-dimensional graphene oxide (GO). Without extra addition of bio/chemical stimulators, the microsized GO imparted various immune activation tactics to improve the antigen immunogenicity. A high antigen adsorption was acquired, and the mechanism was revealed to be a combination of electrostatic, hydrophobic, and π-π stacking interactions. The ``folding GO'' acted as a cytokine self-producer and antigen reservoir and showed a particular autophagy, which efficiently promoted the activation of antigen presenting cells (APCs) and subsequent antigen cross-presentation. Such a ``One but All'' modality thus induced a high level of anti-tumor responses in a programmable way and resulted in efficient tumor regression in vivo. This work may shed light on the potential use of a new dimensional nano-platform in the development of high-performance cancer vaccines. Electronic

Cost-effectiveness analysis of prophylactic cervical cancer vaccination in Japanese women.

Science.gov (United States)

Konno, Ryo; Sasagawa, Toshiyuki; Fukuda, Takashi; Van Kriekinge, Georges; Demarteau, Nadia

2010-04-01

The incidence of cervical cancer (CC) is high in Japan and is further increasing among women younger than 30 years. This burden could be reduced by the implementation of a CC vaccine, but its cost-effectiveness is unknown. We quantified the clinical impact and assessed the cost-effectiveness of adding CC vaccination at age 12 to the current screening in place in Japan with a lifetime Markov model adapted to the Japanese setting. Transition probabilities and utility values were obtained from public databases. Direct costs for treatment and screening were estimated using Japanese medical fees. Annual costs and benefits were discounted at 3%. Sensitivity analyses were conducted on the age at vaccination, the vaccine characteristics, the discount rates, the proportion of human papillomavirus types 16/18 in cancer, and the screening coverage. Vaccinating a 12-year-old cohort was predicted to reduce CC incidence and deaths from CC by 73%. These clinical effects were associated with an incremental cost-effectiveness ratio of yen1.8 million per quality-adjusted life year gained. The incremental cost-effectiveness ratio of vaccinating all 10- to 45-year-old women was yen2.8 million per quality-adjusted life year, still below the threshold value. The implementation of a CC vaccination in Japan could reduce the CC burden in a very cost-effective manner for women up to 45 years.

Expected effect of vaccination using bivalent vaccine on incidence of cervical dysplasia and cervical cancer in terms of health care system in Slovak Republic

International Nuclear Information System (INIS)

Bielik, J.; Marusakova, E.; Masak, L.

2011-01-01

Purpose: Human papillomavirus is a dominant cause of cervical dysplasia with possible transition to cervical cancer. The main purpose of the study was to make a qualified forecast of the potential of vaccination using a bivalent vaccine on the incidence of cervical dysplasia and cervical cancer as well as disease-related mortality in the Slovak Republic. Methods: The method of evaluation was the use of the Markov model that is strictly based on either epidemiological data from official institutions such as the National Oncology Register of the Slovak Republic, Statistic Office of the Slovak Republic, or the data from health insurance companies and the opinion of the experts´ panel of the Society of Gynaecology and Obstetrics. Results: Results obtained by modelling suggest that the introduction of HPV vaccination into the national immunization programme would result in a reduction of at least 84 deaths of women during the monitored period. Every cervical cancer death averted means 31 life years saved on average. Depending on the vaccination coverage in the cohort, HPV vaccination would cause a reduction of registered cervical dysplasia by 26,900 to 131,808 cases, a reduction of registered carcinoma in situ by 1,371 to 6,714 cases, and a decrease of registered invasive cervical carcinoma by 1,645 to 8,058 cases. Conclusion: The results of the analysis confirmed that HPV vaccination in 12-year old girls has the potential to significantly reduce both the incidence of cervical dysplasia and cervical cancer and mortality due to cervical cancer, whereby this form of primary intervention is also cost-effective. Vaccination also enhances the effect of standard secondary prevention realized by age dependant screening. (author)

Cancer chemoprevention and cancer preventive vaccines--a call to action: leaders of diverse stakeholder groups present strategies for overcoming multiple barriers to meet an urgent need.

Science.gov (United States)

Herberman, Ronald B; Pearce, Homer L; Lippman, Scott M; Pyenson, Bruce S; Alberts, David S

2006-12-15

The emerging field of cancer prevention through chemoprevention agents and cancer vaccines offers significant promise for reducing suffering and death from cancer. However, that promise may not be kept unless major barriers to progress are lowered or eliminated. Among the most significant barriers are the relatively small investment from government and industry in research and development of cancer preventive agents; a predominant emphasis of translational cancer research on therapeutic interventions for metastatic or advanced cancer; complexities of prevention trial design; a relatively uncharted Food and Drug Administration (FDA) approval process for preventive agents; insufficient public and patient understanding of the importance and potential for cancer preventive measures, with consequent unpredictable public and patient willingness to take preventive agents; an uncertain reimbursement from payors; and limitations in patent law, liability protection, and data package exclusivity that undermine the opportunity for recouping investment. Viewed individually or collectively, each of these barriers serves as a substantial deterrent to intellectual and financial investment by all sectors of the cancer community. In an effort to ultimately overcome these barriers, a Cancer Prevention Research Summit was assembled June 12-13, 2006 in Bethesda, Maryland, organized by C-Change with support from the AACR. The Summit brought together some 120 leaders from private, public, and not-for-profit entities, including cancer researchers and clinicians; federal health officials; regulatory agency representatives; pharmaceutical, biotech, and food industry leaders; patent attorneys; economists; public and private provider group executives; and advocates. Participants engaged in a detailed process to more carefully define the major barriers, identify potential solutions, and formulate initial priorities and recommendations for action. At the conclusion of this dialogue among

The virus and the vaccine: the true story of a cancer-causing monkey virus, contaminated polio vaccine, and the millions of Americans exposed

National Research Council Canada - National Science Library

Bookchin, Debbie; Schumacher, Jim

2004-01-01

.... But now SV40 in showing up in human cancers, and prominent researchers are demanding a serious public health response to this forgotten polio vaccine contaminant. A gripping medical detective story, The Virus and the Vaccine raises major questions about vaccine policy.

[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.

Cancer registries and monitoring the impact of prophylactic human papillomavirus vaccines: the potential role.

Science.gov (United States)

Saraiya, Mona; Goodman, Marc T; Datta, S Deblina; Chen, Vivien W; Wingo, Phyllis A

2008-11-15

The recent US Food and Drug Administration licensure of a prophylactic vaccine against oncogenic human papillomavirus (HPV) types 16 and 18, the first of its kind, poses unique challenges in postmarketing vaccine surveillance, especially in measuring vaccine effectiveness against biologic endpoints of HPV infection. Historically, the national system of population-based cancer registries in the US has provided high-quality data on cancer incidence and mortality for the most important biologic endpoints, namely, anogenital cancers and some oral cavity/oropharyngeal cancers. There also has been some data collection on cancer precursors; however, this activity has been inconsistent and of lower priority. Because effectiveness against HPV-associated cancers will not be measurable for several decades, strengthening and possibly expanding the capacity of registries to collect precancer data, which are earlier manifestations of infection, must be considered. Collecting type-specific data on HPV-associated precancers and cancers. While keeping in mind the current limitations of registry operations, they discuss resources that may be needed to implement and sustain these types of activities.

Global challenges of implementing human papillomavirus vaccines

Directory of Open Access Journals (Sweden)

Mishra Amrita

2011-06-01

Full Text Available Abstract Human Papillomavirus vaccines are widely hailed as a sweeping pharmaceutical innovation for the universal benefit of all women. The implementation of the vaccines, however, is far from universal or equitable. Socio-economically marginalized women in emerging and developing, and many advanced economies alike, suffer a disproportionately large burden of cervical cancer. Despite the marketing of Human Papillomavirus vaccines as the solution to cervical cancer, the market authorization (licensing of the vaccines has not translated into universal equitable access. Vaccine implementation for vulnerable girls and women faces multiple barriers that include high vaccine costs, inadequate delivery infrastructure, and lack of community engagement to generate awareness about cervical cancer and early screening tools. For Human Papillomavirus vaccines to work as a public health solution, the quality-assured delivery of cheaper vaccines must be integrated with strengthened capacity for community-based health education and screening.

New strategies to improve the efficacy of colorectal cancer vaccines: from bench to bedside.

Science.gov (United States)

Mocellin, Simone

2006-12-01

By exploiting a naturally occurring defense system, anticancer vaccination embodies an ideal non-toxic treatment capable of evoking tumor-specific immune responses that can ultimately recognize and kill colorectal cancer (CRC) cells. Despite the enormous theoretical potential of active specific immunotherapy, no vaccination regimen has achieved sufficient therapeutic efficacy necessary for clinical implementation. Nevertheless, several immunological advances have opened new avenues of research to decipher the biological code governing tumor immune responsiveness, and this is leading to the design of potentially more effective immunotherapeutic protocols. This review briefly summarizes the principles behind anti-CRC vaccination and describes the most promising immunological strategies that have been developed, which are expected to renew interest in this molecularly targeted anticancer approach.

Therapeutic Cancer Vaccines in Combination with Conventional Therapy

DEFF Research Database (Denmark)

Andersen, Mads Hald; Junker, N.; Ellebaek, E.

2010-01-01

The clinical efficacy of most therapeutic vaccines against cancer has not yet met its promise. Data are emerging that strongly support the notion that combining immunotherapy with conventional therapies, for example, radiation and chemotherapy may improve efficacy. In particular combination...

Therapeutic cancer vaccines in combination with conventional therapy

DEFF Research Database (Denmark)

Andersen, Mads Hald; Junker, Niels; Ellebaek, Eva

2010-01-01

The clinical efficacy of most therapeutic vaccines against cancer has not yet met its promise. Data are emerging that strongly support the notion that combining immunotherapy with conventional therapies, for example, radiation and chemotherapy may improve efficacy. In particular combination...

Harnessing naturally occurring tumor immunity: a clinical vaccine trial in prostate cancer.

Directory of Open Access Journals (Sweden)

Mayu O Frank

2010-09-01

Full Text Available Studies of patients with paraneoplastic neurologic disorders (PND have revealed that apoptotic tumor serves as a potential potent trigger for the initiation of naturally occurring tumor immunity. The purpose of this study was to assess the feasibility, safety, and immunogenicity of an apoptotic tumor-autologous dendritic cell (DC vaccine.We have modeled PND tumor immunity in a clinical trial in which apoptotic allogeneic prostate tumor cells were used to generate an apoptotic tumor-autologous dendritic cell vaccine. Twenty-four prostate cancer patients were immunized in a Phase I, randomized, single-blind, placebo-controlled study to assess the safety and immunogenicity of this vaccine. Vaccinations were safe and well tolerated. Importantly, we also found that the vaccine was immunogenic, inducing delayed type hypersensitivity (DTH responses and CD4+ and CD8+ T cell proliferation, with no effect on FoxP3+ regulatory T cells. A statistically significant increase in T cell proliferation responses to prostate tumor cells in vitro (p = 0.002, decrease in prostate specific antigen (PSA slope (p = 0.016, and a two-fold increase in PSA doubling time (p = 0.003 were identified when we compared data before and after vaccination.An apoptotic cancer cell vaccine modeled on naturally occurring tumor immune responses in PND patients provides a safe and immunogenic tumor vaccine.ClinicalTrials.gov NCT00289341.

Cervical cancer treatment costs and cost-effectiveness analysis of human papillomavirus vaccination in Vietnam: a PRIME modeling study.

Science.gov (United States)

Van Minh, Hoang; My, Nguyen Thi Tuyet; Jit, Mark

2017-05-15

Cervical cancer is currently the leading cause of cancer mortality among women in South Vietnam and the second leading cause of cancer mortality in North Vietnam. Human papillomavirus (HPV) vaccination has the potential to substantially decrease this burden. The World Health Organization (WHO) recommends that a cost-effectiveness analysis of HPV vaccination is conducted before nationwide introduction. The Papillomavirus Rapid Interface for Modeling and Economics (PRIME) model was used to evaluate the cost-effectiveness of HPV vaccine introduction. A costing study based on expert panel discussions, interviews and hospital case note reviews was conducted to explore the cost of cervical cancer care. The cost of cervical cancer treatment ranged from US$368 - 11400 depending on the type of hospital and treatment involved. Under Gavi-negotiated prices of US$4.55, HPV vaccination is likely to be very cost-effective with an incremental cost per disability-adjusted life year (DALY) averted in the range US$780 - 1120. However, under list prices for Cervarix and Gardasil in Vietnam, the incremental cost per DALY averted for HPV vaccination can exceed US$8000. HPV vaccine introduction appears to be economically attractive only if Vietnam is able to procure the vaccine at Gavi prices. This highlights the importance of initiating a nationwide vaccination programme while such prices are still available.

Predictors of Adults' Knowledge and Awareness of HPV, HPV-Associated Cancers, and the HPV Vaccine: Implications for Health Education.

Science.gov (United States)

McBride, Kimberly R; Singh, Shipra

2018-02-01

High human papillomavirus (HPV) prevalence and low HPV vaccine uptake are significant public health concerns. Disparities in HPV-associated cancers and HPV vaccine uptake rates suggest the need for additional research examining factors associated with vaccine acceptance. This study assessed HPV awareness and knowledge and identified sociodemographic characteristics associated with HPV knowledge at the population level. Data from adult men ( n = 1,197) and women ( n = 1,906) who participated in the National Cancer Institute's 2014 Health Information National Trends Survey were analyzed. Multivariable regression was used to identify predictors of four HPV knowledge categories: (1) general knowledge, (2) cervical cancer knowledge, (3) "other" cancer knowledge (i.e., anal, oral, penile), and (4) vaccine knowledge. Significant gender differences in awareness and knowledge of HPV and the HPV vaccine were revealed. Most participants (>70%) knew that HPV could cause cervical cancer, but fewer (14.9% to 31.5%) knew of the association between HPV and "other" cancers. Women were more likely to report that a health care provider recommended vaccination. Significant predictors of general HPV and HPV vaccine knowledge included gender, education, income, race, and other sociodemographic characteristics. Age and income predicted cervical cancer knowledge. Knowledge of "other" HPV-associated cancers was predicted by having a child under 18 years in the household and relationship status. HPV knowledge appears to be socially patterned. Low HPV knowledge among men and some racial minorities suggests a need for further intervention. Health education should emphasize risks of noncervical HPV-associated cancers. Patient-provider communication that includes education, counseling, and clear recommendations favoring vaccination may improve uptake.

Psychosocial predictors of human papillomavirus vaccination intentions for young women 18 to 26: religiosity, morality, promiscuity, and cancer worry.

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Krakow, Melinda M; Jensen, Jakob D; Carcioppolo, Nick; Weaver, Jeremy; Liu, Miao; Guntzviller, Lisa M

2015-01-01

To determine whether five psychosocial variables, namely, religiosity, morality, perceived promiscuity, cancer worry frequency, and cancer worry severity, predict young women's intentions to receive the human papillomavirus (HPV) vaccination. Female undergraduate students (n=408) completed an online survey. Questions pertaining to hypothesized predictors were analyzed through bivariate correlations and hierarchical regression equations. Regressions examined whether the five psychosocial variables of interest predicted intentions to vaccinate above and beyond controls. Proposed interactions among predictor variables were also tested. Study findings supported cancer worry as a direct predictor of HPV vaccination intention, and religiosity and sexual experience as moderators of the relationship between concerns of promiscuity reputation and intentions to vaccinate. One dimension of cancer worry (severity) emerged as a particularly robust predictor for this population. This study provides support for several important, yet understudied, factors contributing to HPV vaccination intentions among college-aged women: cancer worry severity and religiosity. Future research should continue to assess the predictive contributions of these variables and evaluate how messages and campaigns to increase HPV vaccination uptake can utilize religious involvement and worry about cancer to promote more effectively HPV vaccination as a cancer prevention strategy. Copyright © 2015 Jacobs Institute of Women's Health. Published by Elsevier Inc. All rights reserved.

Macromolecular systems for vaccine delivery.

Science.gov (United States)

MuŽíková, G; Laga, R

2016-10-20

Vaccines have helped considerably in eliminating some life-threatening infectious diseases in past two hundred years. Recently, human medicine has focused on vaccination against some of the world's most common infectious diseases (AIDS, malaria, tuberculosis, etc.), and vaccination is also gaining popularity in the treatment of cancer or autoimmune diseases. The major limitation of current vaccines lies in their poor ability to generate a sufficient level of protective antibodies and T cell responses against diseases such as HIV, malaria, tuberculosis and cancers. Among the promising vaccination systems that could improve the potency of weakly immunogenic vaccines belong macromolecular carriers (water soluble polymers, polymer particels, micelles, gels etc.) conjugated with antigens and immunistumulatory molecules. The size, architecture, and the composition of the high molecular-weight carrier can significantly improve the vaccine efficiency. This review includes the most recently developed (bio)polymer-based vaccines reported in the literature.

Acceptability of human papilloma virus vaccine and cervical cancer ...

African Journals Online (AJOL)

2012-07-14

Jul 14, 2012 ... names in a prepared sampling frame of each group of workers, and thereafter ... Following individual counseling of eligible participants, .... Stanley M. Human Papilloma Virus Vaccines versus cervical cancer screening.

Efficacy and safety of human papillomavirus vaccine for primary prevention of cervical cancer: A review of evidence from phase III trials and national programs

Directory of Open Access Journals (Sweden)

Partha Basu

2013-01-01

Full Text Available The Human Papillomavirus (HPV vaccines have been widely introduced in the national immunization programs in most of the medium and high income countries following endorsement from national and international advisory bodies. HPV vaccine is unique and its introduction is challenging in many ways - it is the first vaccine developed to prevent any cancer, the vaccine is gender specific, it targets adolescent females who are difficult to reach by any health intervention programs. It is not unusual for such a vaccine to face scepticism and reservations not only from lay public but also from professionals in spite of the clinical trial results convincingly and consistently proving their efficacy and safety. Over the last few years millions of doses of the HPV vaccine have been administered round the world and the efficacy and safety data have started coming from the real life programs. A comprehensive cervical cancer control program involving HPV vaccination of the adolescent girls and screening of the adult women has been proved to be the most cost-effective approach to reduce the burden of cervical cancer. The present article discusses the justification of HPV vaccination in the backdrop of natural history of cervical cancer, the mechanism of action of the vaccines, efficacy and safety data from phase III randomized controlled trials as well as from the national immunization programs of various countries.

Scaling up cervical cancer screening in the midst of human papillomavirus vaccination advocacy in Thailand

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Teerawattananon Yot

2010-07-01

Full Text Available Abstract Background Screening tests for cervical cancer are effective in reducing the disease burden. In Thailand, a Pap smear program has been implemented throughout the country for 40 years. In 2008 the Ministry of Public Health (MoPH unexpectedly decided to scale up the coverage of free cervical cancer screening services, to meet an ambitious target. This study analyzes the processes and factors that drove this policy innovation in the area of cervical cancer control in Thailand. Methods In-depth interviews with key policy actors and review of relevant documents were conducted in 2009. Data analysis was guided by a framework, developed on public policy models and existing literature on scaling-up health care interventions. Results Between 2006 and 2008 international organizations and the vaccine industry advocated the introduction of Human Papillomavirus (HPV vaccine for the primary prevention of cervical cancer. Meanwhile, a local study suggested that the vaccine was considerably less cost-effective than cervical cancer screening in the Thai context. Then, from August to December 2008, the MoPH carried out a campaign to expand the coverage of its cervical cancer screening program, targeting one million women. The study reveals that several factors were influential in focusing the attention of policymakers on strengthening the screening services. These included the high burden of cervical cancer in Thailand, the launch of the HPV vaccine onto the global and domestic markets, the country’s political instability, and the dissemination of scientific evidence regarding the appropriateness of different options for cervical cancer prevention. Influenced by the country’s political crisis, the MoPH’s campaign was devised in a very short time. In the view of the responsible health officials, the campaign was not successful and indeed, did not achieve its ambitious target. Conclusion The Thai case study suggests that the political crisis was a

Scaling up cervical cancer screening in the midst of human papillomavirus vaccination advocacy in Thailand.

Science.gov (United States)

Yothasamut, Jomkwan; Putchong, Choenkwan; Sirisamutr, Teera; Teerawattananon, Yot; Tantivess, Sripen

2010-07-02

Screening tests for cervical cancer are effective in reducing the disease burden. In Thailand, a Pap smear program has been implemented throughout the country for 40 years. In 2008 the Ministry of Public Health (MoPH) unexpectedly decided to scale up the coverage of free cervical cancer screening services, to meet an ambitious target. This study analyzes the processes and factors that drove this policy innovation in the area of cervical cancer control in Thailand. In-depth interviews with key policy actors and review of relevant documents were conducted in 2009. Data analysis was guided by a framework, developed on public policy models and existing literature on scaling-up health care interventions. Between 2006 and 2008 international organizations and the vaccine industry advocated the introduction of Human Papillomavirus (HPV) vaccine for the primary prevention of cervical cancer. Meanwhile, a local study suggested that the vaccine was considerably less cost-effective than cervical cancer screening in the Thai context. Then, from August to December 2008, the MoPH carried out a campaign to expand the coverage of its cervical cancer screening program, targeting one million women. The study reveals that several factors were influential in focusing the attention of policymakers on strengthening the screening services. These included the high burden of cervical cancer in Thailand, the launch of the HPV vaccine onto the global and domestic markets, the country's political instability, and the dissemination of scientific evidence regarding the appropriateness of different options for cervical cancer prevention. Influenced by the country's political crisis, the MoPH's campaign was devised in a very short time. In the view of the responsible health officials, the campaign was not successful and indeed, did not achieve its ambitious target. The Thai case study suggests that the political crisis was a crucial factor that drew the attention of policymakers to the cervical

Current Status of HPV Vaccines

Science.gov (United States)

Ma, Barbara; Roden, Richard; Wu, T.C.

2010-01-01

Cervical cancer is the second largest cause of cancer deaths in women worldwide, with ~500,000 diagnoses and 274,000 deaths annually. It remains a significant source of morbidity and mortality despite effective screening tools and treatments for its precursor high-grade cervical intraepithelial neoplasia (CIN). Increased understanding of cervical pathogenesis has led to the identification of human papillomavirus (HPV) as the etiological agent for cervical cancer and the development of preventive and therapeutic vaccines targeting HPV antigens for the control of cervical cancer. Herein, we discuss the current status of HPV vaccines. PMID:20677402

Human papilloma virus vaccination in Nepal: an initial experience in Nepal.

Science.gov (United States)

Singh, Yogendra; Shah, Aarti; Singh, Meeta; Verma, Sheela; Shrestha, Bhakta Man; Vaidya, Prabhu; Nakarmi, Radha Pyari; Shrestha, Surendra Bb

2010-01-01

Cervical cancer is the most common cancer among women in Nepal. Human papilloma virus (HPV) infection, a recognized cause of cervical cancer, is very common in sexually active women and HPV vaccination has been recommended as a prophylactic therapy. If HPV infection is prevented by the HPV vaccination to the adolescent girls, cervical cancer is also prevented. We received 3,300 vials of quadrivalent human papilloma virus (types 6, 11, 16, 18) recombinant vaccine (Gardasil; Merck and Co.) as a gift from the Australian Cervical Cancer Foundation (ACCF) which has a mission to provide life-saving HPV cervical cancer vaccines for women in developing countries, who cannot otherwise afford vaccination. HPV vaccine was offered to 1,096 of 10 to 26 year aged girls attending 17 secondary schools. In total, 1,091 (99.5%) received the second dose and 1,089 (99.3%) received the third dose of the vaccine. The remaining 5 girls at second dose and 2 girls at third dose remained unvaccinated. No serious vaccine related adverse events were reported except mild pain at the injection site in 7.8% of the vaccine recipients. High cost and low public awareness are the key barriers for successful implementation of the vaccination program in resource limited developing countries. In conclusion, HPV vaccine is safe with high acceptability in Nepalese school girls. However a large population study for longer follow up is warranted to validate the findings of this vaccination program.

Collaborative vaccine development: partnering pays.

Science.gov (United States)

Ramachandra, Rangappa

2008-01-01

Vaccine development, supported by infusions of public and private venture capital, is re-entering a golden age as one of the fastest growing sectors in the life-sciences industry. Demand is driven by great unmet need in underdeveloped countries, increased resistance to current treatments, bioterrorism, and for prevention indications in travelers, pediatric, and adult diseases. Production systems are becoming less reliant on processes such as egg-based manufacturing, while new processes can help to optimize vaccines. Expeditious development hinges on efficient study conduct, which is greatly enhanced through research partnerships with specialized contract research organizations (CROs) that are licensed and knowledgeable in the intricacies of immunology and with the technologic and scientific foundation to support changing timelines and strategies inherent to vaccine development. The CRO often brings a more objective assessment for probability of success and may offer alternative development pathways. Vaccine developers are afforded more flexibility and are free to focus on innovation and internal core competencies. Functions readily outsourced to a competent partner include animal model development, safety and efficacy studies, immunotoxicity and immunogenicity, dose response studies, and stability and potency testing. These functions capitalize on the CRO partner's regulatory and scientific talent and expertise, and reduce infrastructure expenses for the vaccine developer. Successful partnerships result in development efficiencies, elimination or reduced redundancies, and improved time to market. Keys to success include honest communications, transparency, and flexibility.

Health and economic impact of HPV 16/18 vaccination and cervical cancer screening in Eastern Africa.

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Campos, Nicole G; Kim, Jane J; Castle, Philip E; Ortendahl, Jesse D; O'Shea, Meredith; Diaz, Mireia; Goldie, Sue J

2012-06-01

Eastern Africa has the world's highest cervical cancer incidence and mortality rates. We used epidemiologic data from Kenya, Mozambique, Tanzania, Uganda, and Zimbabwe to develop models of HPV-related infection and disease. For each country, we assessed HPV vaccination of girls before age 12 followed by screening with HPV DNA testing once, twice, or three times per lifetime (at ages 35, 40, 45). For women over age 30, we assessed only screening (with HPV DNA testing up to three times per lifetime or VIA at age 35). Assuming no waning immunity, mean reduction in lifetime cancer risk associated with vaccination ranged from 36 to 45%, and vaccination followed by screening once per lifetime at age 35 with HPV DNA testing ranged from 43 to 51%. For both younger and older women, the most effective screening strategy was HPV DNA testing three times per lifetime. Provided the cost per vaccinated girl was less than I$10 (I$2 per dose), vaccination had an incremental cost-effectiveness ratio [I$ (international dollars)/year of life saved (YLS)] less than the country-specific per capita GDP, a commonly cited heuristic for "very cost-effective" interventions. If the cost per vaccinated girl was between I$10 (I$2 per dose) and I$25 (I$5 per dose), vaccination followed by HPV DNA testing would save the most lives and would be considered good value for public health dollars. These results should be used to catalyze design and evaluation of HPV vaccine delivery and screening programs, and contribute to a dialogue on financing HPV vaccination in poor countries. Copyright © 2011 UICC.

Human papillomavirus vaccination in the prevention of cervical neoplasia.

LENUS (Irish Health Repository)

Astbury, Katharine

2012-02-01

Cervical cancer remains a major cause of morbidity and mortality for women worldwide. Although the introduction of comprehensive screening programs has reduced the disease incidence in developed countries, it remains a major problem in the developing world. The recent licensing of 2 vaccines against human papillomavirus (HPV) type 16 and HPV-18, the viruses responsible for 70% of cervical cancer cases, offers the hope of disease prevention. In this article, we review the role of HPV in the etiology of cervical cancer and the evidence to support the introduction of vaccination programs in young women and discuss the potential obstacles to widespread vaccination. In addition, we discuss the issues that remain to be elucidated, including the potential need for booster doses of the vaccine and the role of concomitant vaccination in men.

First-in-man application of a novel therapeutic cancer vaccine formulation with the capacity to induce multi-functional T cell responses in ovarian, breast and prostate cancer patients

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Berinstein Neil L

2012-08-01

Full Text Available Abstract Background DepoVaxTM is a novel non-emulsion depot-forming vaccine platform with the capacity to significantly enhance the immunogenicity of peptide cancer antigens. Naturally processed HLA-A2 restricted peptides presented by breast, ovarian and prostate cancer cells were used as antigens to create a therapeutic cancer vaccine, DPX-0907. Methods A phase I clinical study was designed to examine the safety and immune activating potential of DPX-0907 in advanced stage breast, ovarian and prostate cancer patients. A total of 23 late stage cancer patients were recruited and were divided into two dose/volume cohorts in a three immunization protocol. Results DPX-0907 was shown to be safe with injection site reactions being the most commonly reported adverse event. All breast cancer patients (3/3, most of ovarian (5/6 and one third of prostate (3/9 cancer patients exhibited detectable immune responses, resulting in a 61% immunological response rate. Immune responses were generally observed in patients with better disease control after their last prior treatment. Antigen-specific responses were detected in 73% of immune responders (44% of evaluable patients after the first vaccination. In 83% of immune responders (50% of evaluable patients, peptide-specific T cell responses were detected at ≥2 time points post vaccination with 64% of the responders (39% of evaluable patients showing evidence of immune persistence. Immune monitoring also demonstrated the generation of antigen-specific T cell memory with the ability to secrete multiple Type 1 cytokines. Conclusions The novel DepoVax formulation promotes multifunctional effector memory responses to peptide-based tumor associated antigens. The data supports the capacity of DPX-0907 to elicit Type-1 biased immune responses, warranting further clinical development of the vaccine. This study underscores the importance of applying vaccines in clinical settings in which patients are more likely to be

Application of radiation technology in vaccines development.

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Seo, Ho Seong

2015-07-01

One of the earliest methods used in the manufacture of stable and safe vaccines is the use of chemical and physical treatments to produce inactivated forms of pathogens. Although these types of vaccines have been successful in eliciting specific humoral immune responses to pathogen-associated immunogens, there is a large demand for the development of fast, safe, and effective vaccine manufacturing strategies. Radiation sterilization has been used to develop a variety of vaccine types, because it can eradicate chemical contaminants and penetrate pathogens to destroy nucleic acids without damaging the pathogen surface antigens. Nevertheless, irradiated vaccines have not widely been used at an industrial level because of difficulties obtaining the necessary equipment. Recent successful clinical trials of irradiated vaccines against pathogens and tumors have led to a reevaluation of radiation technology as an alternative method to produce vaccines. In the present article, we review the challenges associated with creating irradiated vaccines and discuss potential strategies for developing vaccines using radiation technology.

Anti-cancer vaccination by transdermal delivery of antigen peptide-loaded nanogels via iontophoresis.

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Toyoda, Mao; Hama, Susumu; Ikeda, Yutaka; Nagasaki, Yukio; Kogure, Kentaro

2015-04-10

Transdermal vaccination with cancer antigens is expected to become a useful anti-cancer therapy. However, it is difficult to accumulate enough antigen in the epidermis for effective exposure to Langerhans cells because of diffusion into the skin and muscle. Carriers, such as liposomes and nanoparticles, may be useful for the prevention of antigen diffusion. Iontophoresis, via application of a small electric current, is a noninvasive and efficient technology for transdermal drug delivery. Previously, we succeeded in the iontophoretic transdermal delivery of liposomes encapsulating insulin, and accumulation of polymer-based nanoparticle nanogels in the stratum corneum of the skin. Therefore, in the present study, we examined the use of iontophoresis with cancer antigen gp-100 peptide KVPRNQDWL-loaded nanogels for anti-cancer vaccination. Iontophoresis resulted in the accumulation of gp-100 peptide and nanogels in the epidermis, and subsequent increase in the number of Langerhans cells in the epidermis. Moreover, tumor growth was significantly suppressed by iontophoresis of the antigen peptide-loaded nanogels. Thus, iontophoresis of the antigen peptide-loaded nanogels may serve as an effective transdermal delivery system for anti-cancer vaccination. Copyright © 2015 Elsevier B.V. All rights reserved.

Model for product development of vaccines against neglected tropical diseases: a vaccine against human hookworm.

Science.gov (United States)

Bottazzi, Maria Elena; Brown, Ami Shah

2008-12-01

This article provides an overview of the advances in product development and technology transfer of the vaccine against human hookworm, with particular emphasis on the lessons learned and the challenges of developing a vaccine in the nonprofit sector. The comprehensive approach to vaccine development established by the Human Hookworm Vaccine Initiative (HHVI) identifies key operational and technical aspects that are essential for a successful partnership with a developing country vaccine manufacturer. This article also highlights the importance of a global access roadmap to guide the vaccine development program. The advancement of new products for the control of neglected tropical diseases portends great challenges for global access, including aspects related to vaccine design, product development and manufacture, vaccine introduction and distribution, financing, knowledge dissemination and intellectual property management. With only three vaccines for neglected tropical diseases in clinical trials - hookworm, leishmaniasis and schistosomiasis - we are at the nascent stages of developing vaccines for neglected populations. Product development public-private partnerships, such as the HHVI, continue to show great promise on this front and will eventually provide significant control tools for achieving millennium development goals related to poverty reduction, as well as child and maternal health.

[Seroconversion in response to a reinforced primary hepatitis B vaccination in children with cancer].

Science.gov (United States)

Villena, Rodolfo; Zubieta, Marcela; Hurtado, Carmen; Salgado, Carmen; Silva, Gladys; Fernández, Jazmine; Villarroel, Milena; Fernández, Marisol; Brahm, Javier; O'Ryan, Miguel; Santolaya, María Elena

2015-01-01

Immune response against vaccine antigens may be impaired in children with cancer. The aim of this study was to evaluate the seroconversion response against hepatitis B vaccination (HBV) at the time of chemotherapy onset and/or remission in children with cancer. Prospective, two-centre, controlled, non-randomised study conducted on children recently diagnosed with cancer, paired with healthy subjects. Cases received HBV at time 0, 1 and 6 months with DNA recombinant HBV at a dose of 20 and 40 μg if than 10 years of age, respectively, at the time of diagnosis for solids tumours and after the remission in case of haematological tumours. Controls received the same schedule, but at of 10 and 20 μg doses, respectively. HBs antibodies were measured in serum samples obtained at 2, 8 and 12 months post-vaccination. Protective titres were defined as > 10 mIU/ml at 8th month of follow up. A total of 78 children with cancer and 25 healthy controls were analysed at month 8th of follow up. Seroconversion rates in the cancer group reached 26.9%, with no differences by age, gender or type of tumour (P = .13, .29, and .44, respectively). Control group seroconversion was 100% at the 8th month, with P 10 mIU/ml. Vaccination against hepatitis B with three doses of DNA recombinant vaccine at an increased concentration, administrated at the time of onset of chemotherapy and/or remission provided an insufficient immune response in a majority of children with cancer. More immunogenic vaccines should be evaluated in this special population, such as a third generation, with more immunogenic adjuvants, enhanced schedules at 0, 1, 2, 6 month, evaluation of antibody titres at month 8 and 12h to evaluate the need for further booster doses. Copyright © 2015 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

TAPCells, the Chilean dendritic cell vaccine against melanoma and prostate cancer

Directory of Open Access Journals (Sweden)

Flavio Salazar-Onfray

2013-01-01

Full Text Available Here we summarize 10 years of effort in the development of a biomedical innovation with global projections. This innovation consists of a novel method for the production of therapeutic dendritic-like cells called Tumor Antigen Presenting Cells (TAPCells®. TAPCells-based immunotherapy was tested in more than 120 stage III and IV melanoma patients and 20 castration-resistant prostate cancer patients in a series of phase I and I/II clinical trials. TAPCells vaccines induced T cell-mediated memory immune responses that correlated with increased survival in melanoma patients and prolonged prostate-specific antigen doubling time in prostate cancer patients. Importantly, more than 60% of tested patients showed a Delayed Type Hypersensitivity (DTH reaction against the lysates, indicating the development of anti-tumor immunological memory that correlates with clinical benefits. The in vitro analysis of the lysate mix showed that it contains damage-associated molecular patterns such as HMBG-1 protein which are capable to improve, through Toll-like receptor-4, maturation and antigen cross-presentation of the dendritic cells (DC. In fact, a Toll-like receptor-4 polymorphism correlates with patient clinical outcomes. Moreover, Concholepas concholepas hemocyanin (CCH used as adjuvant proved to be safe and capable of enhancing the immunological response. Furthermore, we observed that DC vaccination resulted in a three-fold increase of T helper-1 lymphocytes releasing IFN-γ and a two-fold increase of T helper-17 lymphocytes capable of producing IL-17 in DTH+ with respect to DTH- patients. Important steps have been accomplished for TAPCells technology transfer, including patenting, packaging and technology assessment. Altogether, our results indicate that TAPCells vaccines constitute an exceptional Chilean national innovation of international value.

TAPCells, the Chilean dendritic cell vaccine against melanoma and prostate cancer.

Science.gov (United States)

Salazar-Onfray, Flavio; Pereda, Cristián; Reyes, Diego; López, Mercedes N

2013-01-01

Here we summarize 10 years of effort in the development of a biomedical innovation with global projections. This innovation consists of a novel method for the production of therapeutic dendritic-like cells called Tumor Antigen Presenting Cells (TAPCells®). TAPCells-based immunotherapy was tested in more than 120 stage III and IV melanoma patients and 20 castration-resistant prostate cancer patients in a series of phase I and I/II clinical trials. TAPCells vaccines induced T cell-mediated memory immune responses that correlated with increased survival in melanoma patients and prolonged prostate-specific antigen doubling time in prostate cancer patients. Importantly, more than 60% of tested patients showed a Delayed Type Hypersensitivity (DTH) reaction against the lysates, indicating the development of anti-tumor immunological memory that correlates with clinical benefits. The in vitro analysis of the lysate mix showed that it contains damage-associated molecular patterns such as HMBG-1 protein which are capable to improve, through Toll-like receptor-4, maturation and antigen cross-presentation of the dendritic cells (DC). In fact, a Toll-like receptor-4 polymorphism correlates with patient clinical outcomes. Moreover, Concholepas concholepas hemocyanin (CCH) used as adjuvant proved to be safe and capable of enhancing the immunological response. Furthermore, we observed that DC vaccination resulted in a three-fold increase of T helper-1 lymphocytes releasing IFN-γ and a two-fold increase of T helper-17 lymphocytes capable of producing IL-17 in DTH+ with respect to DTH- patients. Important steps have been accomplished for TAPCells technology transfer, including patenting, packaging and technology assessment. Altogether, our results indicate that TAPCells vaccines constitute an exceptional Chilean national innovation of international value.

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.

Estimation of the epidemiological burden of HPV-related anogenital cancers, precancerous lesions, and genital warts in women and men in Europe: Potential additional benefit of a nine-valent second generation HPV vaccine compared to first generation HPV vaccines

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Susanne Hartwig

2015-12-01

Full Text Available Introduction: A second generation HPV vaccine has been developed for the prevention of anogenital cancers and precancerous lesions of the cervix, vulva, vagina, anus and of genital warts due to nine HPV types.We estimated the annual burden of these diseases attributable to the nine HPV types compared to HPV types from first generation vaccines in women and men in Europe. Material and methods: Incidence rates from the IARC database, cancer registries, the literature and Eurostat population data were used.The burden attributable to the HPV types targeted by both vaccines was estimated by applying the relative contribution of the respective HPV types from epidemiological studies. Results: In 2013, the number of new anogenital HPV-attributable cancers was 44,480 with 39,494 of these cases related to second vs. 33,285 to first generation vaccine types.Among the 284,373 to 541,621 new HPV-attributable anogenital precancerous lesions 235,364–448,423 and 135,025–256,830 were estimated to be related to second and first generation vaccine types, respectively.The annual number of new genital warts was 753,608–935,318, with 90% related to HPV6/11. Conclusions: These data demonstrate how the large public health impact that was achieved by the first generation HPV vaccines could be further increased by second generation vaccines. Keywords: HPV, Burden of disease, Cancer, Precancerous lesions, Genital warts, HPV vaccine

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

Preclinical development of a vaccine 'against smoking'.

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Cerny, E H; Lévy, R; Mauel, J; Mpandi, M; Mutter, M; Henzelin-Nkubana, C; Patiny, L; Tuchscherer, G; Cerny, T

2002-10-01

Nicotine is the main culprit for dependence on tobacco-containing products, which in turn are a major etiologic factor for cardiovascular diseases and cancer. This publication describes a vaccine, which elicits antibodies against nicotine. The antibodies in the blood stream intercept the nicotine molecule on its way to its receptors and greatly diminish the nicotine influx to the brain shortly after smoking. The nicotine molecule is chemically linked to cholera toxin B as a carrier protein in order to induce antibodies. The potential to elicit antibodies after subcutaneous as well as intranasal immunization is evaluated. In order to simulate realistic conditions, nicotine pumps delivering the nicotine equivalent of 5 packages of cigarettes for 4 weeks are implanted into the mice 1 week prior to vaccination. The protective effect of the vaccine is measured 5 weeks after vaccination by comparing the influx of radiolabeled nicotine in the brains of vaccinated and non-vaccinated animals 5 min after challenge with the nicotine equivalent of 2 cigarettes. The polyclonal antibodies induced by the vaccine show a mean avidity of 1.8 x 10(7) l/Mol. Subcutaneous immunization elicits high antibody levels of the IgG class, and significant IgA antibody levels in the saliva of vaccinated mice can be found after intranasal vaccination. The protective effect also in the animals with implanted nicotine pumps is significant: less than 10% of radiolabeled nicotine found in the brains of non-vaccinated animals can be found in the brains of vaccinated animals. These data provide credible evidence that a vaccine can break the vicious circle between smoking and instant gratification by intercepting the nicotine molecule. Astonishingly, there is no sign of exhaustion of specific antibodies even under extreme conditions, which makes it highly unlikely that a smoker can overcome the protective effect of the vaccine by smoking more. Finally, the high titers of specific antibodies after 1 year

Progress in Brucella vaccine development

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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

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

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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.

Advances and challenges in malaria vaccine development.

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Crompton, Peter D; Pierce, Susan K; Miller, Louis H

2010-12-01

Malaria caused by Plasmodium falciparum remains a major public health threat, especially among children and pregnant women in Africa. An effective malaria vaccine would be a valuable tool to reduce the disease burden and could contribute to elimination of malaria in some regions of the world. Current malaria vaccine candidates are directed against human and mosquito stages of the parasite life cycle, but thus far, relatively few proteins have been studied for potential vaccine development. The most advanced vaccine candidate, RTS,S, conferred partial protection against malaria in phase II clinical trials and is currently being evaluated in a phase III trial in Africa. New vaccine targets need to be identified to improve the chances of developing a highly effective malaria vaccine. A better understanding of the mechanisms of naturally acquired immunity to malaria may lead to insights for vaccine development.

Knowledge and Awareness of Cervical Cancer, Human Papillomavirus (HPV), and HPV Vaccine Among HPV-Infected Chinese Women.

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Baloch, Zulqarnain; Yasmeen, Nafeesa; Li, Yuanyue; Zhang, Wenhui; Lu, Hongyu; Wu, Xiaomei; Xia, Xueshan; Yang, Shihua

2017-09-04

BACKGROUND It is important to understand the knowledge that various groups of a population have about cervical cancer and human papillomavirus (HPV) and their attitudes toward HPV vaccination, as it will ultimately influence their decision-making for or against the acceptability of vaccines and other preventive methods. This study was designed to determine the level of knowledge and awareness about cervical cancer, HPV, and the HPV vaccine among Chinese women in Yunnan province. MATERIAL AND METHODS A survey was conducted in Yunnan province by the Laboratory of Molecular Virology in collaboration with the Yunnan First People's Hospital in Feb 2015. A total of 388 women were recruited and asked to participate in a questionnaire-based interview that collected information related to their awareness and knowledge about: (1) cervical cancer, (2) HPV and HPV vaccine and willingness to have their children receive vaccination, and (3) demographic characteristics. RESULTS A total of 388 HPV-positive women were included; 300/388 (73.3%) were Han, and 88/388 (22.7%) were other ethnicities. Overall, 204/388 (52.6%) of the women were aware of cervical cancer, with a significant difference between Han women and women of other ethnic groups (168/388, 56.0% and 36/88, 40.9%; P=0.015). Overall, 26.5% of the women were aware of the role of HPV in cervical cancer; 29.0% of the Han women and 18.2% of women of other ethnic groups were aware of this role of HPV (P=0.05). The knowledge that HPV infection leads to cervical cancer was higher among Han women (29.0%) compared to women of other ethnicities (18.2%). Knowledge about the HPV vaccine was very low in all ethnic groups, but the Han women were more willing to allow their children to be vaccinated before they become sexually active. A similar difference has also been found in women from various regions. CONCLUSIONS Although level of awareness and knowledge about cervical cancer was moderate, knowledge and awareness of HPV and the HPV

Integrating epidemiology, psychology, and economics to achieve HPV vaccination targets.

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Basu, Sanjay; Chapman, Gretchen B; Galvani, Alison P

2008-12-02

Human papillomavirus (HPV) vaccines provide an opportunity to reduce the incidence of cervical cancer. Optimization of cervical cancer prevention programs requires anticipation of the degree to which the public will adhere to vaccination recommendations. To compare vaccination levels driven by public perceptions with levels that are optimal for maximizing the community's overall utility, we develop an epidemiological game-theoretic model of HPV vaccination. The model is parameterized with survey data on actual perceptions regarding cervical cancer, genital warts, and HPV vaccination collected from parents of vaccine-eligible children in the United States. The results suggest that perceptions of survey respondents generate vaccination levels far lower than those that maximize overall health-related utility for the population. Vaccination goals may be achieved by addressing concerns about vaccine risk, particularly those related to sexual activity among adolescent vaccine recipients. In addition, cost subsidizations and shifts in federal coverage plans may compensate for perceived and real costs of HPV vaccination to achieve public health vaccination targets.

Adherence to cervical cancer screening varies by human papillomavirus vaccination status in a high-risk population

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Christopher A. Paynter

2015-01-01

Full Text Available Cervical cancer screening has reduced the incidence of cervical cancer over the past 75 years. The primary aim of this study was to determine if women receiving Gardasil™ (HPV4 vaccine participated in future cervical cancer screening at the same rate as that observed for unvaccinated women matched on birth year and health care campus. This is a retrospective cohort study of subjects selected from 27,786 females born from 1980 to 1992 who received health care in the Truman Medical Center safety net health system in Kansas City Missouri, USA. 1154 women 14–26 years old who received at least one dose of HPV4 vaccine between 2006 and 2009 were chosen at random from the vaccine records. 1154 randomly chosen unvaccinated women were age and health campus matched to the vaccinated women and all were followed until July 1, 2013. Women who were screened after 21 years and received three vaccine doses before 21 years, had the lowest screening rate of 24%. Their only predictive factor for screening, compared to the unvaccinated, was being closer to 21 years than 14 years at vaccination (aOR = 1.71 95% CI: 1.45, 2.00. Women vaccinated with three doses and screened at or after 21 years had the highest screening rate of 84% predicting a six-fold increase in screening participation over no vaccine received (aOR = 5.94 95% CI: 3.77, 9.35. Our results suggest that women who receive HPV4 vaccination closer to 21 years, not 14, are more likely to participate in cervical cancer screening in an underserved US population.

Development of Streptococcus agalactiae vaccines for tilapia.

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Liu, Guangjin; Zhu, Jielian; Chen, Kangming; Gao, Tingting; Yao, Huochun; Liu, Yongjie; Zhang, Wei; Lu, Chengping

2016-12-21

Vaccination is a widely accepted and effective method to prevent most pathogenic diseases in aquaculture. Various species of tilapia, especially Nile tilapia Oreochromis niloticus, are farmed worldwide because of their high consumer demand. Recently, the tilapia-breeding industry has been hampered by outbreaks of Streptococcus agalactiae infection, which cause high mortality and huge economic losses. Many researchers have attempted to develop effective S. agalactiae vaccines for tilapia. This review provides a summary of the different kinds of S. agalactiae vaccines for tilapia that have been developed recently. Among the various vaccine types, inactivated S. agalactiae vaccines showed superior protection efficiency when compared with live attenuated, recombinant and DNA vaccines. With respect to vaccination method, injecting the vaccine into tilapia provided the most effective immunoprotection. Freund's incomplete adjuvant appeared to be suitable for tilapia vaccines. Other factors, such as immunization duration and number, fish size and challenge dose, also influenced the vaccine efficacy.

A prospective highlight on exosomal nanoshuttles and cancer immunotherapy and vaccination

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Mohammad A. Rafi

2015-08-01

Conclusions: As complex systems, these vesicular micro-/nano-machines convey important cellular messages dependent upon the cells/tissue setting(s. In addition to their potential in diagnosis of cancers, they have been exploited for cancer immunotherapy/vaccination. However, such treatment strategies need to be carefully designed to attain desired clinical outcomes.

Vaccines against enteric infections for the developing world

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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

[Human papillomavirus nonavalent vaccine. Update 2017].

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Bosch, F X; Moreno, D; Redondo, E; Torné, A

Human papillomavirus (HPV) is the causative agent of 5% of human cancers. HPV infection is necessary for the development of cervical cancer and is responsible of a variable percentage of cancers of anus, vulva, vagina, penis, and oropharynx. Since 2007, 2 vaccines against HPV have been commercially available in Spain: bivalent (HPV types 16/18), and tetravalent (HPV types 6/11/16/18). In order to extend the protection afforded by HPV vaccines, a clinical program was launched in 2006 for the new nonavalent vaccine, including 9 HPV types (6/11/16/18/31/33/45/52/58). These types are responsible for 90% of cervical cancers, 82% of high-grade ano-genital pre-cancerous lesions, and 90% of genital warts. The purpose of this publication is to provide healthcare professionals with the scientific evidence that supports the new vaccine, as well as the clinical value that it offers in our environment. Copyright © 2017 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

Microneedle patches for vaccination in developing countries.

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Arya, Jaya; Prausnitz, Mark R

2016-10-28

Millions of people die of infectious diseases each year, mostly in developing countries, which could largely be prevented by the use of vaccines. While immunization rates have risen since the introduction of the Expanded Program on Immunization (EPI), there remain major challenges to more effective vaccination in developing countries. As a possible solution, microneedle patches containing an array of micron-sized needles on an adhesive backing have been developed to be used for vaccine delivery to the skin. These microneedle patches can be easily and painlessly applied by pressing against the skin and, in some designs, do not leave behind sharps waste. The patches are single-dose, do not require reconstitution, are easy to administer, have reduced size to simplify storage, transportation and waste disposal, and offer the possibility of improved vaccine immunogenicity, dose sparing and thermostability. This review summarizes vaccination challenges in developing countries and discusses advantages that microneedle patches offer for vaccination to address these challenges. We conclude that microneedle patches offer a powerful new technology that can enable more effective vaccination in developing countries. Copyright © 2015. Published by Elsevier B.V.

HIV vaccines: new frontiers in vaccine development.

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Duerr, Ann; Wasserheit, Judith N; Corey, Lawrence

2006-08-15

A human immunodeficiency virus (HIV) vaccine is the most promising and feasible strategy to prevent the events during acute infection that simultaneously set the course of the epidemic in the community and the course of the disease for the individual. Because safety concerns limit the use of live, attenuated HIV and inactivated HIV, a variety of alternate approaches is being investigated. Traditional antibody-mediated approaches using recombinant HIV envelope proteins have shown no efficacy in 2 phase III trials. Current HIV vaccine trials are focusing primarily on cytotoxic T lymphocyte-mediated products that use viral vectors, either alone or as boosts to DNA plasmids that contain viral genes. The most immunogenic of these products appear to be the recombinant adenovirus vector vaccines, 2 of which are now in advanced clinical development.

PD-L1 peptide co-stimulation increases immunogenicity of a dendritic cell-based cancer vaccine

DEFF Research Database (Denmark)

Munir Ahmad, Shamaila; Martinenaite, Evelina; Hansen, Morten

2016-01-01

elicited by the DC vaccine even further. Consequently, we observed a significant increase in the number of vaccine-reacting T cells in vitro. In conclusion, activation of PD-L1-specific T cells may directly modulate immunogenicity of DC vaccines. Addition of PD-L1 epitopes may thus be an easily applicable...... and attractive option to augment the effectiveness of cancer vaccines and other immunotherapeutic agents....

Conjugate Meningococcal Vaccines Development: GSK Biologicals Experience

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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.

Conjugate Meningococcal Vaccines Development: GSK Biologicals Experience

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Miller, Jacqueline M.; Mesaros, Narcisa; Van Der Wielen, Marie; Baine, Yaela

2011-01-01

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. PMID:21991444

Design of therapeutic vaccines as a novel antibody therapy for cardiovascular diseases.

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Nakagami, Hironori

2017-09-01

Vaccines are primarily used worldwide as a preventive medicine for infectious diseases and have recently been applied to cancer. We and others have developed therapeutic vaccines designed for cardiovascular diseases that are notably different from previous vaccines. In the case of cancer vaccines, a specific protein in cancer cells is a target antigen, and the activation of cytotoxic T cells (CTL) is required to kill and remove the antigen-presenting cancer cells. Our therapeutic vaccines work against hypertension by targeting angiotensin II (Ang II) as the antigen, which is an endogenous hormone. Therapeutic vaccines must avoid CTL activation and induce the blocking antibodies for Ang II. The goal of our therapeutic vaccine for cardiovascular diseases is to induce the specific antibody response toward the target protein without inducing T-cell or antibody-mediated inflammation through the careful selection of the target antigen, carrier protein and adjuvants. The goal of our therapeutic vaccine is similar to that of antibody therapy. Recently, multiple antibody-based drugs have been developed for cancer, immune-related diseases, and dyslipidemia, which are efficient but expensive. If the effect of a therapeutic vaccine is nearly equivalent to antibody therapy as an alternative approach, the lower medical cost and improvement in drug adherence can be advantages of therapeutic vaccines. In this review, we will describe our concept of therapeutic vaccines for cardiovascular diseases and the future directions of therapeutic vaccines as novel antibody therapies. Copyright © 2017. Published by Elsevier Ltd.

Knowledge of Saudi female university students regarding cervical cancer and acceptance of the human papilloma virus vaccine.

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Al-Shaikh, Ghadeer K; Almussaed, Eman M; Fayed, Amel A; Khan, Farida H; Syed, Sadiqa B; Al-Tamimi, Tahani N; Elmorshedy, Hala N

2014-10-01

To assess the level of knowledge regarding cervical cancer and the acceptance of the human papilloma virus (HPV) vaccine among Saudi female students in health colleges. This cross-sectional study of a convenient sample encompassed 1400 students in Health Colleges at Princess Nora Bint Abdul Rahman University, Riyadh, Saudi Arabia was conducted between December 2013 and February 2014. A self-administrated questionnaire was distributed to all participants. Data collected included socio-demographic data, knowledge of cervical cancer risk factors and clinical presentation, Pap smear, and HPV vaccine acceptance. The questionnaire reliability as tested by Cronbach's alpha was 0.82. The response rate was 89.9%, and data analysis revealed that 95.7% of students had poor knowledge level. The Pap smear was poorly recognized as a screening tool, with 46.7% of students having heard of the test. Senior and medical students had a significantly higher knowledge score. Father's health profession, high monthly income, and presence of cervical cancer among family members or friends increased the level of knowledge. Vaccine acceptance is influenced by its price, approximately 80% of students thought that an affordable vaccine price should not exceed 300 Saudi Riyals. Perceived barriers to the vaccine were fear of injections and vaccine side effects. There is a lack of knowledge and misinformation regarding cervical cancer, Pap smear, and HPV as a major risk factor for cancer of the cervix. These data can be used as a benchmark to formulate effective awareness programs. 

Development of Mycoplasma hyopneumoniae Recombinant Vaccines.

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Marchioro, Silvana Beutinger; Simionatto, Simone; Dellagostin, Odir

2016-01-01

Mycoplasma hyopneumoniae is the etiological agent of swine enzootic pneumonia (EP), a disease that affects swine production worldwide. Vaccination is the most cost-effective strategy for the control and prevention of the disease. Research using genome-based approach has the potential to elucidate the biology and pathogenesis of M. hyopneumoniae and contribute to the development of more effective vaccines. Here, we describe the protocol for developing M. hyopneumoniae recombinant vaccines using reverse vaccinology approaches.

Parental acceptance of HPV vaccine in Peru: a decision framework.

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Rosario M Bartolini

Full Text Available Cervical cancer is the third most common cancer affecting women worldwide and it is an important cause of death, especially in developing countries. Cervical cancer is caused by human papillomavirus (HPV and can be prevented by HPV vaccine. The challenge is to expand vaccine availability to countries where it is most needed. In 2008 Peru's Ministry of Health implemented a demonstration project involving 5(th grade girls in primary schools in the Piura region. We designed and conducted a qualitative study of the decision-making process among parents of girls, and developed a conceptual model describing the process of HPV vaccine acceptance.We found a nonlinear HPV decision-making process that evolved over time. Initially, the vaccine's newness, the requirement of written consent, and provision of information were important. If information was sufficient and provided by credible sources, many parents accepted the vaccine. Later, after obtaining additional information from teachers, health personnel, and other trusted sources, more parents accepted vaccination. An understanding of the issues surrounding the vaccine developed, parents overcome fears and rumors, and engaged in family negotiations-including hearing the girl's voice in the decision-making process. The concept of prevention (cancer as danger, future health, and trust in vaccines combined with pragmatic factors (no cost, available at school and the credibility of the offer (information in the media, recommendation of respected authority figure were central to motivations that led parents to decide to vaccinate their daughters. A lack of confidence in the health system was the primary inhibitor of vaccine acceptance.Health personnel and teachers are credible sources of information and can provide important support to HPV vaccination campaigns.

Vaccines against enteric infections for the developing world.

Science.gov (United States)

Czerkinsky, Cecil; Holmgren, Jan

2015-06-19

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. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

mRNA Cancer Vaccines-Messages that Prevail.

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Grunwitz, Christian; Kranz, Lena M

2017-01-01

During the last decade, mRNA became increasingly recognized as a versatile tool for the development of new innovative therapeutics. Especially for vaccine development, mRNA is of outstanding interest and numerous clinical trials have been initiated. Strikingly, all of these studies have proven that large-scale GMP production of mRNA is feasible and concordantly report a favorable safety profile of mRNA vaccines. Induction of T-cell immunity is a multi-faceted process comprising antigen acquisition, antigen processing and presentation, as well as immune stimulation. The effectiveness of mRNA vaccines is critically dependent on making the antigen(s) of interest available to professional antigen-presenting cells, especially DCs. Efficient delivery of mRNA into DCs in vivo remains a major challenge in the mRNA vaccine field. This review summarizes the principles of mRNA vaccines and highlights the importance of in vivo mRNA delivery and recent advances in harnessing their therapeutic potential.

Photochemical Internalization of Peptide Antigens Provides a Novel Strategy to Realize Therapeutic Cancer Vaccination

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Markus Haug

2018-04-01

Full Text Available Effective priming and activation of tumor-specific CD8+ cytotoxic T lymphocytes (CTLs is crucial for realizing the potential of therapeutic cancer vaccination. This requires cytosolic antigens that feed into the MHC class I presentation pathway, which is not efficiently achieved with most current vaccination technologies. Photochemical internalization (PCI provides an emerging technology to route endocytosed material to the cytosol of cells, based on light-induced disruption of endosomal membranes using a photosensitizing compound. Here, we investigated the potential of PCI as a novel, minimally invasive, and well-tolerated vaccination technology to induce priming of cancer-specific CTL responses to peptide antigens. We show that PCI effectively promotes delivery of peptide antigens to the cytosol of antigen-presenting cells (APCs in vitro. This resulted in a 30-fold increase in MHC class I/peptide complex formation and surface presentation, and a subsequent 30- to 100-fold more efficient activation of antigen-specific CTLs compared to using the peptide alone. The effect was found to be highly dependent on the dose of the PCI treatment, where optimal doses promoted maturation of immature dendritic cells, thus also providing an adjuvant effect. The effect of PCI was confirmed in vivo by the successful induction of antigen-specific CTL responses to cancer antigens in C57BL/6 mice following intradermal peptide vaccination using PCI technology. We thus show new and strong evidence that PCI technology holds great potential as a novel strategy for improving the outcome of peptide vaccines aimed at triggering cancer-specific CD8+ CTL responses.

Determination of knowledge levels, attitude and behaviors of female university students concerning cervical cancer, human papiloma virus and its vaccine.

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Yörük, Selda; Açıkgöz, Ayla; Ergör, Gül

2016-08-03

The purpose of the study is to investigate knowledge, attitudes and behaviours concerning cervical cancer, HPV and HPV vaccine of female students studying at a university in a health related department and explore variables affecting taking the vaccine. The research group consists of female students attending a health related department in Balıkesir University. The data of this cross-sectional research was collected via surveys. The average total knowledge score of the students concerning risks, symptoms and screening methods of cervical cancer and HPV vaccines was 14.15 ± 6.7. The HPV knowledge score of the students attending the faculty of medicine was higher compared to the students attending other departments and their HPV vaccine knowledge score was higher compared to the students attending nursing and paramedics students. The HPV vaccine knowledge score of the students attending the department of midwifery was significantly higher compared to other students. Only 0.9 % of the students took the vaccine. One third of the students who did not take the vaccine did not know that the vaccine was available in our country. In terms of the department that they attended, the students with a higher total knowledge score compared to the average (OR:1.5) and students with history of cancer in their families (OR:1.6) were more likely to consider taking the vaccine. Research group's knowledge on risk factors of cervical cancer, Pap smear test, symptoms and prevention ways of cancer, HPV and HPV vaccine was low.

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

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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

ALA-PDT mediated DC vaccine for skin squamous cell carcinoma

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Ji, Jie; Fan, Zhixia; Zhou, Feifan; Wang, Xiaojie; Shi, Lei; Zhang, Haiyan; Wang, Peiru; Yang, Degang; Zhang, Linglin; Wang, Xiuli; Chen, Wei R.

2015-03-01

Dendritic cell (DC) based vaccine has emerged as a promising immunotherapy for cancers. However, most DC vaccines so far have only achieved limited success in cancer treatment. Photodynamic therapy (PDT), an established cancer treatment strategy, can cause immunogenic apoptosis to induce an effective antitumor immune response. In this study, we developed a DC-based cancer vaccine using immunogenic apoptotic tumor cells induced by 5-aminolevulinic acid (ALA) mediated PDT. The maturation of DCs induced by PDT-treated apoptotic cells was evaluated. The anti-tumor immunity of ALA-PDT-DC vaccine was tested with mouse model. We observed the maturations of DCs potentiated by ALA-PDT treated tumor cells, including phenotypic maturation (upregulation of surface expression of MHC-II, DC80, and CD86), and functional maturation (enhanced capability to secret INF-Υ and IL-12). ALA-PDT-DC vaccine mediated by apoptotic cells provided protection against tumor in mice, far stronger than that of DC vaccine obtained from freeze/thaw treated tumor cells. Our results indicate that immunogenic apoptotic tumor cells can be more effective in enhancing DC-based cancer vaccine, which could improve the clinical application of PDT- DC vaccines.

Engineering nanoparticle-coated bacteria as oral DNA vaccines for cancer immunotherapy.

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Hu, Qinglian; Wu, Min; Fang, Chun; Cheng, Changyong; Zhao, Mengmeng; Fang, Weihuan; Chu, Paul K; Ping, Yuan; Tang, Guping

2015-04-08

Live attenuated bacteria are of increasing importance in biotechnology and medicine in the emerging field of cancer immunotherapy. Oral DNA vaccination mediated by live attenuated bacteria often suffers from low infection efficiency due to various biological barriers during the infection process. To this end, we herein report, for the first time, a new strategy to engineer cationic nanoparticle-coated bacterial vectors that can efficiently deliver oral DNA vaccine for efficacious cancer immunotherapy. By coating live attenuated bacteria with synthetic nanoparticles self-assembled from cationic polymers and plasmid DNA, the protective nanoparticle coating layer is able to facilitate bacteria to effectively escape phagosomes, significantly enhance the acid tolerance of bacteria in stomach and intestines, and greatly promote dissemination of bacteria into blood circulation after oral administration. Most importantly, oral delivery of DNA vaccines encoding autologous vascular endothelial growth factor receptor 2 (VEGFR2) by this hybrid vector showed remarkable T cell activation and cytokine production. Successful inhibition of tumor growth was also achieved by efficient oral delivery of VEGFR2 with nanoparticle-coated bacterial vectors due to angiogenesis suppression in the tumor vasculature and tumor necrosis. This proof-of-concept work demonstrates that coating live bacterial cells with synthetic nanoparticles represents a promising strategy to engineer efficient and versatile DNA vaccines for the era of immunotherapy.

Acceptability of human papilloma virus vaccine and cervical cancer ...

African Journals Online (AJOL)

Aim: To determine the awareness and acceptability of the HPV vaccine and screening for cervical cancer among female health-care workers in Enugu, southeastern Nigeria. Materials and Methods: Questionnaires were administered to a cross-section of 177 female health-care workers selected systematically from the ...

Nanotechnology and vaccine development

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Mi-Gyeong Kim

2014-10-01

Full Text Available Despite the progress of conventional vaccines, improvements are clearly required due to concerns about the weak immunogenicity of these vaccines, intrinsic instability in vivo, toxicity, and the need for multiple administrations. To overcome such problems, nanotechnology platforms have recently been incorporated into vaccine development. Nanocarrier-based delivery systems offer an opportunity to enhance the humoral and cellular immune responses. This advantage is attributable to the nanoscale particle size, which facilitates uptake by phagocytic cells, the gut-associated lymphoid tissue, and the mucosa-associated lymphoid tissue, leading to efficient antigen recognition and presentation. Modifying the surfaces of nanocarriers with a variety of targeting moieties permits the delivery of antigens to specific cell surface receptors, thereby stimulating specific and selective immune responses. In this review, we introduce recent advances in nanocarrier-based vaccine delivery systems, with a focus on the types of carriers, including liposomes, emulsions, polymer-based particles, and carbon-based nanomaterials. We describe the remaining challenges and possible breakthroughs, including the development of needle-free nanotechnologies and a fundamental understanding of the in vivo behavior and stability of the nanocarriers in nanotechnology-based delivery systems.

Leishmaniasis vaccine candidates for development: a global overview.

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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.

Next Generation Immunotherapy for Pancreatic Cancer: DNA Vaccination is Seeking New Combo Partners.

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Cappello, Paola; Curcio, Claudia; Mandili, Giorgia; Roux, Cecilia; Bulfamante, Sara; Novelli, Francesco

2018-02-16

Pancreatic Ductal Adenocarcinoma (PDA) is an almost incurable radio- and chemo-resistant tumor, and its microenvironment is characterized by a strong desmoplastic reaction associated with a significant infiltration of T regulatory lymphocytes and myeloid-derived suppressor cells (Tregs, MDSC). Investigating immunological targets has identified a number of metabolic and cytoskeletal related molecules, which are typically recognized by circulating antibodies. Among these molecules we have investigated alpha-enolase (ENO1), a glycolytic enzyme that also acts a plasminogen receptor. ENO1 is also recognized by T cells in PDA patients, so we developed a DNA vaccine that targets ENO1. This efficiently induces many immunological processes (antibody formation and complement-dependent cytotoxicity (CDC)-mediated tumor killing, infiltration of effector T cells, reduction of infiltration of myeloid and Treg suppressor cells), which significantly increase the survival of genetically engineered mice that spontaneously develop pancreatic cancer. Although promising, the ENO1 DNA vaccine does not completely eradicate the tumor, which, after an initial growth inhibition, returns to proliferate again, especially when Tregs and MDSC ensue in the tumor mass. This led us to develop possible strategies for combinatorial treatments aimed to broaden and sustain the antitumor immune response elicited by DNA vaccination. Based on the data we have obtained in recent years, this review will discuss the biological bases of possible combinatorial treatments (chemotherapy, PI3K inhibitors, tumor-associated macrophages, ENO1 inhibitors) that could be effective in amplifying the response induced by the immune vaccination in PDA.

Knowledge of Saudi female university students regarding cervical cancer and acceptance of the human papilloma virus vaccine

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Al-Shaikh, Ghadeer K.; Almussaed, Eman M.; Fayed, Amel A.; Khan, Farida H.; Syed, Sadiqa B.; Al-Tamimi, Tahani N.; Elmorshedy, Hala N.

2014-01-01

Objectives: To assess the level of knowledge regarding cervical cancer and the acceptance of the human papilloma virus (HPV) vaccine among Saudi female students in health colleges. Methods: This cross-sectional study of a convenient sample encompassed 1400 students in Health Colleges at Princess Nora Bint Abdul Rahman University, Riyadh, Saudi Arabia was conducted between December 2013 and February 2014. A self-administrated questionnaire was distributed to all participants. Data collected included socio-demographic data, knowledge of cervical cancer risk factors and clinical presentation, Pap smear, and HPV vaccine acceptance. The questionnaire reliability as tested by Cronbach’s alpha was 0.82. Results: The response rate was 89.9%, and data analysis revealed that 95.7% of students had poor knowledge level. The Pap smear was poorly recognized as a screening tool, with 46.7% of students having heard of the test. Senior and medical students had a significantly higher knowledge score. Father’s health profession, high monthly income, and presence of cervical cancer among family members or friends increased the level of knowledge. Vaccine acceptance is influenced by its price, approximately 80% of students thought that an affordable vaccine price should not exceed 300 Saudi Riyals. Perceived barriers to the vaccine were fear of injections and vaccine side effects. Conclusion: There is a lack of knowledge and misinformation regarding cervical cancer, Pap smear, and HPV as a major risk factor for cancer of the cervix. These data can be used as a benchmark to formulate effective awareness programs. PMID:25316467

DENGUE VACCINE, CHALLENGES, DEVELOPMENT AND STRATEGIES

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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

European guidelines for quality assurance in cervical cancer screening. Summary of the supplements on HPV screening and vaccination

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Lawrence von Karsa

2015-12-01

Full Text Available In a project coordinated by the International Agency for Research on Cancer (IARC 31 experts from 11 European countries and IARC have developed supplements to the current European guidelines for quality assurance in cervical cancer screening. The supplements take into account the potential of primary testing for human papillomavirus (HPV and vaccination against HPV infection to improve cervical cancer prevention and control and will be published by the European Commission in book format. They include 62 recommendations or conclusions for which the strength of the evidence and the respective recommendations is graded. While acknowledging the available evidence for more efficacious screening using HPV primary testing compared to screening based on cytology, the authors and editors of the supplements emphasize that appropriate policy and programme organization remain essential to achieve an acceptable balance between benefit and harm of any screening or vaccination programme. A summary of the supplements and all of the graded recommendations are presented here in journal format to make key aspects of the updated and expanded guidelines known to a wider professional and scientific community. Keywords: Mass screening, Vaccination, Cervical neoplasms, Human papillomavirus, Evidence-based guidelines, Population-based programme

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.

Development of Novel Vaccines against Enterovirus-71

Science.gov (United States)

Yee, Pinn Tsin Isabel; Poh, Chit Laa

2015-01-01

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. PMID:26729152

Vaccine prophylaxis: achievements, problems, perspectives of development

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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.

Beliefs about cervical cancer and human papillomavirus (HPV) and acceptability of HPV vaccination among Chinese women in Hong Kong.

Science.gov (United States)

Lee, Peter W H; Kwan, Tracy T C; Tam, Kar Fai; Chan, Karen K L; Young, Phyllis M C; Lo, Sue S T; Cheung, Annie N Y; Ngan, Hextan Y S

2007-01-01

To assess the knowledge and beliefs on cervical cancer and HPV infection and to evaluate the acceptability of HPV vaccination among Chinese women. Seven focus groups were conducted with ethnic Chinese women aged 18-25 (n=20), 26-35 (n=13), and 36 and above (n=16) in a community women's health clinic in Hong Kong in 2006. The discussions were audio taped, transcribed and analyzed. Recurrent themes related to cervical cancer, HPV infection and vaccination were highlighted. Diverse conceptions on likely causes of cervical cancer were noted, covering biological, psychological, environmental, lifestyle and sexual factors. Most women had not heard of HPV and its mode of transmission. The participants had difficulties understanding and accepting the linkage between cervical cancer and the sexually transmitted HPV infection. HPV infection was seen as personally stigmatizing with significant adverse impact on self-esteem and significant relationships. Participants favored HPV vaccination both for themselves and their teenage daughters if authoritative endorsement was provided. Inadequate knowledge and misconceptions on cervical cancer and HPV were common. Most participants welcomed and favored having HPV vaccination. Apart from promoting HPV vaccination, cervical cancer prevention should also include strategies to promote knowledge and minimize the stigmatizing effect of a sexually transmitted HPV infection.

Zika Vaccine Development: Flavivirus Foils

Science.gov (United States)

2016-09-01

Martins, Bavari, Zika Vaccine Development 1 Zika Vaccine Development: Flavivirus Foils Martins KAO, Bavari S. The current Zika virus...States government. The rapid response to Zika is perhaps the first of its kind, and it undoubtedly has been made possible by the lessons learned from...the response to the 2014 Ebola virus outbreak in West Africa. However, Zika virus is not Ebola virus. As of February 2016 there were only 296

Awareness, knowledge and beliefs about HPV, cervical cancer and HPV vaccines among nurses in Cameroon: an exploratory study.

Science.gov (United States)

Wamai, Richard G; Ayissi, Claudine Akono; Oduwo, Geofrey O; Perlman, Stacey; Welty, Edith; Welty, Thomas; Manga, Simon; Onyango, Monica A; Ogembo, Javier Gordon

2013-10-01

While it is known that sub-Saharan African countries face multiple obstacles such as cost in adopting vaccination against human papillomavirus (HPV), the crucial role nurses can play in implementing such programs has not been adequately examined. To investigate the knowledge and awareness of HPV, primary cause of cervical cancer and HPV vaccine among nurses working at four Cameroon Baptist Convention Health Services facilities, and to explore what factors influence nurses' willingness to inform and recommend HPV vaccine to adolescents and parents attending clinics. A structured questionnaire survey was administered to a convenience sample of nursing staff working at the four health facilities. Of 192 eligible nurses 76 (39.6%) participated in the study. There were moderately low levels of knowledge about HPV infection and prevention of cervical cancer, but a moderately high level of knowledge about HPV vaccine. Although 90.8% acknowledged that cervical cancer is directly linked to HPV infection, nearly 32% failed to identify it as a sexually transmitted infection (STI), while 43.4% believed it is an uncommon infection. Willingness to recommend the HPV vaccine was moderate, with 69.7% intentionally initiating discussions with patients about the subject. The most important factors considered when deciding to recommend the vaccine included effectiveness (56.6%) and side effects/safety (11.8%). Cost was less of a concern (6.6%), likely due to the availability of donated vaccine. Despite high awareness about HPV, more education about the virus, cervical cancer and the vaccine are required to further increase nurses' willingness to recommend the vaccine and strengthen strategies for reaching adolescents through nurses in Cameroon. Published by Elsevier Ltd.

The cancer-immunity cycle as rational design for synthetic cancer drugs: Novel DC vaccines and CAR T-cells.

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Ramachandran, Mohanraj; Dimberg, Anna; Essand, Magnus

2017-08-01

Cell therapy is an advanced form of cancer immunotherapy that has had remarkable clinical progress in the past decade in the search for cure of cancer. Most success has been achieved for chimeric antigen receptor (CAR) T-cells where CAR T-cells targeting CD19 show very high complete response rates for patients with refractory acute B-cell acute lymphoblastic leukemia (ALL) and are close to approval for this indication. CD19 CAR T-cells are also effective against B-cell chronic lymphoblastic leukemia (CLL) and B-cell lymphomas. Although encouraging, CAR T-cells have not yet proven clinically effective for solid tumors. This is mainly due to the lack of specific and homogenously expressed targets to direct the T-cells against and a hostile immunosuppressive tumor microenvironment in solid tumors. Cancer vaccines based on dendritic cells (DC) are also making progress although clinical efficacy is still lacking. The likelihood of success is however increasing now when individual tumors can be sequences and patient-specific neoepitopes identified. Neoepitopes and/or neoantigens can then be included in patient-based DC vaccines. This review discusses recent advancements of DC vaccines and CAR T-cells with emphasis on the cancer-immunity cycle, and current efforts to design novel cell therapies. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Global Vaccine and Immunization Research Forum: Opportunities and challenges in vaccine discovery, development, and delivery.

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Ford, Andrew Q; Touchette, Nancy; Hall, B Fenton; Hwang, Angela; Hombach, Joachim

2016-03-18

The World Health Organization, the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, and the Bill & Melinda Gates Foundation convened the first Global Vaccine and Immunization Research Forum (GVIRF) in March 2014. This first GVIRF aimed to track recent progress of the Global Vaccine Action Plan research and development agenda, identify opportunities and challenges, promote partnerships in vaccine research, and facilitate the inclusion of all stakeholders in vaccine research and development. Leading scientists, vaccine developers, and public health officials from around the world discussed scientific and technical challenges in vaccine development, research to improve the impact of immunization, and regulatory issues. This report summarizes the discussions and conclusions from the forum participants. Copyright © 2016. Published by Elsevier Ltd.. All rights reserved.

Shikonin enhances efficacy of a gene-based cancer vaccine via induction of RANTES

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Chen Hui-Ming

2012-04-01

Full Text Available Abstract Background Shikonin, a phytochemical purified from Lithospermum erythrorhizon, has been shown to confer diverse pharmacological activities, including accelerating granuloma formation, wound healing, anti-inflammation and others, and is explored for immune-modifier activities for vaccination in this study. Transdermal gene-based vaccine is an attractive approach for delivery of DNA transgenes encoding specific tumor antigens to host skin tissues. Skin dendritic cells (DCs, a potent antigen-presenting cell type, is known to play a critical role in transmitting and orchestrating tumor antigen-specific immunities against cancers. The present study hence employs these various components for experimentation. Method The mRNA and protein expression of RANTES were detected by RT-PCR and ELISA, respectively. The regional expression of RANTES and tissue damage in test skin were evaluated via immunohistochemistry assay. Fluorescein isothiocyanate sensitization assay was performed to trace the trafficking of DCs from the skin vaccination site to draining lymph nodes. Adjuvantic effect of shikonin on gene gun-delivered human gp100 (hgp100 DNA cancer vaccine was studied in a human gp100-transfected B16 (B16/hgp100 tumor model. Results Among various phytochemicals tested, shikonin induced the highest level of expression of RANTES in normal skin tissues. In comparison, mouse RANTES cDNA gene transfection induced a higher level of mRANTES expression for a longer period, but caused more extensive skin damage. Topical application of shikonin onto the immunization site before gene gun-mediated vaccination augmented the population of skin DCs migrating into the draining lymph nodes. A hgp100 cDNA gene vaccination regimen with shikonin pretreatment as an adjuvant in a B16/hgp100 tumor model increased cytotoxic T lymphocyte activities in splenocytes and lymph node cells on target tumor cells. Conclusion Together, our findings suggest that shikonin can

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

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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.

Development and trial of vaccines against Brucella.

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Lalsiamthara, Jonathan; Lee, John Hwa

2017-08-31

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 .

Recombinant vaccines and the development of new vaccine strategies

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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.

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.

Recombinant vaccines and the development of new vaccine strategies

International Nuclear Information System (INIS)

Nascimento, I.P.; Leite, L.C.C.

2012-01-01

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

Measuring effectiveness of the cervical cancer vaccine in an Australian setting (the VACCINE study).

Science.gov (United States)

Young, Elisa J; Tabrizi, Sepehr N; Brotherton, Julia Ml; Wark, John D; Pyman, Jan; Saville, Marion; Wrede, C David; Jayasinghe, Yasmin; Tan, Jeffrey; Gertig, Dorota M; Pitts, Marian; Garland, Suzanne M

2013-06-19

specific lesion. Australia is well placed to gain a clear and early insight into the effectiveness of the human papillomavirus vaccine in reducing the prevalence of human papillomavirus infection in young women, and any subsequent reduction in the prevalence of pre-cancerous cervical lesions, specifically high grade cervical intraepithelial neoplasia lesions, particularly of vaccine related types. The findings of a successful population based human papillomavirus program will have wide-reaching translational benefits across the globe.

A New Decade of Vaccines

LENUS (Irish Health Repository)

Murphy, JFA

2011-09-01

The call for a new decade of vaccines was made in December 2010. The aims are to secure the further discovery, development and delivery of vaccination. The first challenge is the acquisition of funds for the research and development of 20 new vaccines1. The Gates Foundation has pledged $10 billion for this venture. The other major players are WHO, UNICEF and the US National Institute of Allergy and Infectious Diseases. The top priorities are TB, AIDS and Malaria. It is hoped that a Malaria vaccine will available in 3 years. The ambitious target of saving the lives of over 7 million children has been set. The programme must also address the need for vaccines in insulin dependent diabetes, cancers and degenerative diseases2.

Knowledge and Attitudes About Human Papilloma Virus (HPV) Vaccination and Cervical Cancer Screening Among Women in Rural Uganda

Science.gov (United States)

2016-06-15

1- Knowledge and attitudes about Human Papilloma Virus (HPV) vaccination and cervical cancer screening among women in rural Uganda Authors...vaccination among parents/guardians of the vaccinated girls and to assess the attitudes to HPV vaccination among parents/guardians of the vaccinated girls...general attitude towards HPV vaccination was positive among mothers though there is still need for the populations to appreciate HPV and cervical

Anti-cancer vaccine therapy for hematologic malignancies: An evolving era.

Science.gov (United States)

Nahas, Myrna R; Rosenblatt, Jacalyn; Lazarus, Hillard M; Avigan, David

2018-02-15

The potential promise of therapeutic vaccination as effective therapy for hematologic malignancies is supported by the observation that allogeneic hematopoietic cell transplantation is curative for a subset of patients due to the graft-versus-tumor effect mediated by alloreactive lymphocytes. Tumor vaccines are being explored as a therapeutic strategy to re-educate host immunity to recognize and target malignant cells through the activation and expansion of effector cell populations. Via several mechanisms, tumor cells induce T cell dysfunction and senescence, amplifying and maintaining tumor cell immunosuppressive effects, resulting in failure of clinical trials of tumor vaccines and adoptive T cell therapies. The fundamental premise of successful vaccine design involves the introduction of tumor-associated antigens in the context of effective antigen presentation so that tolerance can be reversed and a productive response can be generated. With the increasing understanding of the role of both the tumor and tumor microenvironment in fostering immune tolerance, vaccine therapy is being explored in the context of immunomodulatory therapies. The most effective strategy may be to use combination therapies such as anti-cancer vaccines with checkpoint blockade to target critical aspects of this environment in an effort to prevent the re-establishment of tumor tolerance while limiting toxicity associated with autoimmunity. Copyright © 2018 Elsevier Ltd. All rights reserved.

Vaccines against papillomavirus infections and disease

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Villa Luisa Lina

2003-01-01

Full Text Available Squamous cell carcinoma of the uterine cervix is the second cause of cancer-related deaths in women, the higher incidence being observed in developing countries. Infection with oncogenic types of human papillomavirus (HPV is considered the major risk factor for the development of malignancies in the uterine cervix. However, HPV is considered to be a necessary but not sufficient cause for cervical cancer and, therefore, other factors contribute to the carcinogenic process, both present in the environment and from the host. Studies performed in animals, and more recently in humans, indicate that vaccination against the capsid proteins of the virus can prevent efficiently from infection. Furthermore, therapeutic vaccines are under investigation aiming the regression of papillomavirus induced tumors. The scientific basis for the development of papillomavirus vaccines and present status of clinical trials will be addressed in this chapter.

Defining a strategy to evaluate cervical cancer prevention and early detection in the era of HPV vaccination.

Science.gov (United States)

Howlett, Roberta I; Miller, Anthony B; Pasut, George; Mai, Verna

2009-05-01

The purpose of this paper is to outline the short-, medium- and long-term requirements of a strategy to evaluate the impact of HPV immunization and to define a framework to facilitate planning and evaluation. This strategy was developed in Ontario from January to August 2008. Literature review was completed to assess existing material relevant to vaccine evaluation, and HPV vaccine specifically. Scientists and epidemiologists within our organization attended meetings to brainstorm and identify key requirements for vaccine evaluation. Other selected internal and external experts were consulted to review preliminary lists of potential indicators and questions for inclusion in an evaluation strategy. Results are reported in three sections--literature review, proposed evaluation framework and data requirements. The first vaccine evaluation strategy that integrates primary and secondary prevention of cervical cancer is presented. Among women who are neither screened nor immunized, customized interventions will be required to ensure that they are aware of potential risks and benefits. This evaluation strategy may serve as a useful outline for jurisdictions in Canada and elsewhere. This new paradigm of combined primary and secondary intervention will encourage cooperation for effective evaluation of an integrated approach for control of cervical cancer and other HPV-related disease.

Tularemia vaccine development: paralysis or progress?

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Sunagar R

2016-05-01

Full Text Available Raju Sunagar, Sudeep Kumar, Brian J Franz, Edmund J Gosselin Center for Immunology and Microbial Disease, Albany Medical College, Albany, NY, USA Abstract: Francisella tularensis (Ft is a gram-negative intercellular pathogen and category A biothreat agent. However, despite 15 years of strong government investment and intense research focused on the development of a US Food and Drug Administration-approved vaccine against Ft, the primary goal remains elusive. This article reviews research efforts focused on developing an Ft vaccine, as well as a number of important factors, some only recently recognized as such, which can significantly impact the development and evaluation of Ft vaccine efficacy. Finally, an assessment is provided as to whether a US Food and Drug Administration-approved Ft vaccine is likely to be forthcoming and the potential means by which this might be achieved. Keywords: Sex bias, media impact, differential protection, cellular immunity, humoral immunity

Knowledge, attitudes, practices and willingness to vaccinate in preparation for the introduction of HPV vaccines in Bamako, Mali.

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De Groot, Anne S; Tounkara, Karamoko; Rochas, Mali; Beseme, Sarah; Yekta, Shahla; Diallo, Fanta Siby; Tracy, J Kathleen; Teguete, Ibrahima; Koita, Ousmane A

2017-01-01

Although screening for pre-cancerous cervical lesions and human papilloma virus (HPV) vaccination are accepted and effective means to prevent cervical cancer, women in Mali have limited access to these interventions. In addition, cervical cancer prevention by HPV vaccination has been controversial in some settings. To reduce cervical cancer prevalence and increase HPV vaccine uptake, it is important to understand the level of knowledge about cervical cancer screening and practices related to vaccination in at-risk populations. In this study, the level of knowledge about HPV and cervical cancer and attitudes towards vaccination were assessed among 301 participants (male and female, adults and adolescents) in a house-to-house survey in two urban neighborhoods in Bamako, Mali. The survey was combined with a brief educational session on HPV. Prior to the education session, overall knowledge of HPV infection and cervical cancer was very low: only 8% knew that HPV is a sexually transmitted infection (STI). Less than 20% of women had ever consulted a gynecologist and less than 3% had ever had cervical cancer screening. After hearing a description of HPV vaccine, more than 80% would accept HPV vaccination; fathers and husbands were identified as primary decisions makers and local clinics or the home as preferred sites for vaccination. This study provides information on STI knowledge and vaccine acceptance in Bamako, Mali in 2012, prior to the introduction of HPV vaccination.

Parental Acceptance of HPV Vaccine in Peru: A Decision Framework

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Bartolini, Rosario M.; Winkler, Jennifer L.; Penny, Mary E.; LaMontagne, D. Scott

2012-01-01

Objective and Method Cervical cancer is the third most common cancer affecting women worldwide and it is an important cause of death, especially in developing countries. Cervical cancer is caused by human papillomavirus (HPV) and can be prevented by HPV vaccine. The challenge is to expand vaccine availability to countries where it is most needed. In 2008 Peru’s Ministry of Health implemented a demonstration project involving 5th grade girls in primary schools in the Piura region. We designed and conducted a qualitative study of the decision-making process among parents of girls, and developed a conceptual model describing the process of HPV vaccine acceptance. Results We found a nonlinear HPV decision-making process that evolved over time. Initially, the vaccine’s newness, the requirement of written consent, and provision of information were important. If information was sufficient and provided by credible sources, many parents accepted the vaccine. Later, after obtaining additional information from teachers, health personnel, and other trusted sources, more parents accepted vaccination. An understanding of the issues surrounding the vaccine developed, parents overcome fears and rumors, and engaged in family negotiations–including hearing the girl’s voice in the decision-making process. The concept of prevention (cancer as danger, future health, and trust in vaccines) combined with pragmatic factors (no cost, available at school) and the credibility of the offer (information in the media, recommendation of respected authority figure) were central to motivations that led parents to decide to vaccinate their daughters. A lack of confidence in the health system was the primary inhibitor of vaccine acceptance. Conclusions Health personnel and teachers are credible sources of information and can provide important support to HPV vaccination campaigns. PMID:23144719

Cervical cancer screening, human papillomavirus vaccination practices and current infrastructure in Israel.

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Schejter, Eduardo; Bornstein, Jacob; Siegler, Efraim

2013-11-22

The incidence rates for premalignant lesions in Jewish women in Israel are similar to those observed in Western countries, but the incidence of cervical cancer in Israel is low; this discrepancy is not yet clearly understood. Because of the low incidence of cervical cancer in Israel, it was decided to base cervical cancer prevention on opportunistic screening: every woman from the ages of 35-54 years can have a Pap test smear free of charge every 3 years. Over the last decade 12.2% of the women population had an annual Pap test. From 36 to 50% of women who attended the Clalit Health Maintenance Organization (HMO) and the Maccabi HMO, the two largest HMOs in Israel, did so. There were also discrepancies between women of different socio-economic status (SES): Israel Society of Obstetrics and Gynecology recommends continuing cytologic screening in vaccinated women as recommended for the general population. This article forms part of a regional report entitled "Comprehensive Control of HPV Infections and Related Diseases in Israel" Vaccine Volume 31, Supplement 8, 2013. Updates of the progress in the field are presented in a separate monograph entitled "Comprehensive Control of HPV Infections and Related Diseases" Vaccine Volume 30, Supplement 5, 2012. Copyright © 2013. Published by Elsevier Ltd.

Comparative cost-effectiveness of HPV vaccines in the prevention of cervical cancer in Malaysia.

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Ezat, Sharifa W P; Aljunid, Syed

2010-01-01

Cervical cancer (CC) had the second highest incidence of female cancers in Malaysia in 2003-2006. Prevention is possible by both Pap smear screening and HPV vaccination with either the bivalent vaccine (BV) or the quadrivalent vaccine (QV). In the present study, cost effectiveness options were compared for three programs i.e. screening via Pap smear; modeling of HPV vaccination (QV and BV) and combined strategy (screening plus vaccination). A scenario based sensitivity analysis was conducted using screening population coverages (40-80%) and costs of vaccines (RM 100-200/dose) were calculated. This was an economic burden, cross sectional study in 2006-2009 of respondents interviewed from six public Gynecology-Oncology hospitals. Methods included expert panel discussions to estimate treatment costs of CC, genital warts and vulva/vagina cancers by severity and direct interviews with respondents using costing and SF-36 quality of life questionnaires. A total of 502 cervical cancer patients participated with a mean age at 53.3±11.2 years and a mean marriage length of 27.7±12.1 years, Malays accounting for 44.2%. Cost/quality adjusted life year (QALY) for Pap smear in the base case was RM 1,215 and RM 1,100 at increased screening coverage. With QV only, in base case it was RM 15,662 and RM 24,203 when the vaccination price was increased. With BV only, the respective figures were RM 1,359,057 and RM 2,530,018. For QV combined strategy cost/QALY in the base case it was RM 4,937, reducing to RM 3,395 in the best case and rising to RM 7,992 in the worst case scenario. With the BV combined strategy, these three cost/QALYs were RM 6,624, RM 4,033 and RM 10,543. Incremental cost-effectiveness ratio (ICER) showed that screening at 70% coverage or higher was highly cost effective at RM 946.74 per QALYs saved but this was preceded by best case combined strategy with QV at RM 515.29 per QALYs saved. QV is more cost effective than BV. The QV combined strategy had a higher CE than

Vaccine procurement and self-sufficiency in developing countries.

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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.

Dengue vaccines: Challenges, development, current status and prospects

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A Ghosh

2015-01-01

Full Text Available Infection with dengue virus (DENV is the most rapidly spreading mosquito-borne viral disease in the world. The clinical spectrum of dengue, caused by any of the four serotypes of DENV, ranges from mild self-limiting dengue fever to severe dengue, in the form dengue hemorrhagic fever (DHF and dengue shock syndrome (DSS. Increased rates of hospitalization due to severe dengue, during outbreaks, result in massive economic losses and strained health services. In the absence of specific antiviral therapy, control of transmission of DENV by vector management is the sole method available for decreasing dengue-associated morbidity. Since vector control strategies alone have not been able to satisfactorily achieve reduction in viral transmission, the implementation of a safe, efficacious and cost-effective dengue vaccine as a supplementary measure is a high public health priority. However, the unique and complex immunopathology of dengue has complicated vaccine development. Dengue vaccines have also been challenged by critical issues like lack of animal models for the disease and absence of suitable markers of protective immunity. Although no licensed dengue vaccine is yet available, several vaccine candidates are under phases of development, including live attenuated virus vaccines, live chimeric virus vaccines, inactivated virus vaccines, subunit vaccines, DNA vaccines and viral-vectored vaccines. Although some vaccine candidates have progressed from animal trials to phase II and III in humans, a number of issues regarding implementation of dengue vaccine in countries like India still need to be addressed. Despite the current limitations, collaborative effects of regulatory bodies like World Health Organization with vaccine manufacturers and policy makers, to facilitate vaccine development and standardize field trials can make a safe and efficacious dengue vaccine a reality in near future.

Safety and Efficacy Data on Vaccines and Immunization to Human Papillomavirus

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Natalie Kash

2015-04-01

Full Text Available Since the discovery of the causal association between human papillomavirus (HPV and cervical cancer, efforts to develop an effective prophylactic vaccine to prevent high-risk HPV infections have been at the forefront of modern medical research. HPV causes 530,000 cervical cancer cases worldwide, which is the second most common cause of cancer deaths in women; a worldwide collaboration among epidemiologists, molecular biologists, vaccinologists, virologists, and clinicians helped lead to the development of two highly effective prophylactive HPV vaccines. The first, Gardasil, is a quadrivalent vaccine made up of recombinant HPV L1 capsid proteins from the two high-risk HPV types (16/18 responsible for 70% of cervical cancer cases as well as two low-risk HPV types (6/11 which are the causative agent for genital warts. The second, Cervarix, is a bivalent vaccine that was FDA approved three years after Gardasil and is also composed of L1 capsid proteins from HPV types 16/18. This review article focuses on the safety and efficacy data of both FDA-approved vaccines, as well as highlighting a few advances in future HPV vaccines that show promise in becoming additional treatment options for this worldwide disease.

Induction of protective and therapeutic anti-pancreatic cancer immunity using a reconstructed MUC1 DNA vaccine

International Nuclear Information System (INIS)

Rong, Yefei; Jin, Dayong; Wu, Wenchuan; Lou, Wenhui; Wang, Danshong; Kuang, Tiantao; Ni, Xiaoling; Qin, Xinyu

2009-01-01

Pancreatic cancer is a common, highly lethal disease with a rising incidence. MUC1 is a tumor-associated antigen that is over-expressed in pancreatic adenocarcinoma. Active immunotherapy that targets MUC1 could have great treatment value. Here we investigated the preventive and therapeutic effect of a MUC1 DNA vaccine on the pancreatic cancer. MUC1-various tandem repeat units(VNTR) DNA vaccine was produced by cloning one repeat of VNTR and inserting the cloned gene into the pcDNA3.1. In the preventive group, female C57BL/6 mice were immunized with the vaccine, pcDNA3.1 or PBS; and challenged with panc02-MUC1 or panc02 cell. In the therapeutic group the mice were challenged with panc02-MUC1 or panc02 cell, and then immunized with the vaccine, pcDNA3.1 or PBS. The tumor size and the survival time of the animals were compared between these groups. The DNA vaccine pcDNA3.1-VNTR could raise cytotoxic T lymphocyte (CTL) activity specific for MUC1. In the preventive experiment, the mice survival time was significantly longer in the vaccine group than in the control groups (P < 0.05). In the therapeutic experiment, the DNA vaccine prolonged the survival time of the panc02-MUC1-bearing mice (P < 0.05). In both the preventive and therapeutic experiments, the tumor size was significantly less in the vaccine group than in the control groups (P < 0.05). This pcDNA3.1-VNTR vaccine, however, could not prevent the mice attacked by panc02 cells and had no therapeutic effect on the mice attacked by panc02 cells. The MUC1 DNA vaccine pcDNA3.1-VNTR could induce a significant MUC1-specific CTL response; and had both prophylactic and therapeutic effect on panc02-MUC1 tumors. This vaccine might be used as a new adjuvant strategy against pancreatic cancer

Changes in knowledge of cervical cancer following introduction of human papillomavirus vaccine among women at high risk for cervical cancer

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L. Stewart Massad

2015-04-01

Conclusion: Substantial gaps in understanding of HPV and cervical cancer prevention exist despite years of health education. While more effective educational interventions may help, optimal cancer prevention may require opt-out vaccination programs that do not require nuanced understanding.

Senescent cells re-engineered to express soluble programmed death receptor-1 for inhibiting programmed death receptor-1/programmed death ligand-1 as a vaccination approach against breast cancer.

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Chen, Zehong; Hu, Kang; Feng, Lieting; Su, Ruxiong; Lai, Nan; Yang, Zike; Kang, Shijun

2018-06-01

Various types of vaccines have been proposed as approaches for prevention or delay of the onset of cancer by boosting the endogenous immune system. We previously developed a senescent-cell-based vaccine, induced by radiation and veliparib, as a preventive and therapeutic tool against triple-negative breast cancer. However, the programmed death receptor-1/programmed death ligand-1 (PD-1/PD-L1) pathway was found to play an important role in vaccine failure. Hence, we further developed soluble programmed death receptor-1 (sPD1)-expressing senescent cells to overcome PD-L1/PD-1-mediated immune suppression while vaccinating to promote dendritic cell (DC) maturity, thereby amplifying T-cell activation. In the present study, sPD1-expressing senescent cells showed a particularly active status characterized by growth arrest and modified immunostimulatory cytokine secretion in vitro. As expected, sPD1-expressing senescent tumor cell vaccine (STCV/sPD-1) treatment attracted more mature DC and fewer exhausted-PD1 + T cells in vivo. During the course of the vaccine studies, we observed greater safety and efficacy for STCV/sPD-1 than for control treatments. STCV/sPD-1 pre-injections provided complete protection from 4T1 tumor challenge in mice. Additionally, the in vivo therapeutic study of mice with s.c. 4T1 tumor showed that STCV/sPD-1 vaccination delayed tumorigenesis and suppressed tumor progression at early stages. These results showed that STCV/sPD-1 effectively induced a strong antitumor immune response against cancer and suggested that it might be a potential strategy for TNBC prevention. © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

[Ten years of human papillomavirus vaccination. From dermatology to oncology via infectology].

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Moraga-Llop, Fernando A

2018-05-01

Human papillomavirus (HPV) was first identified in dermatology, and it was subsequently demonstrated that is was required for the development of uterine cervical cancer and other tumours, after a persistent infection by any of its oncogenic genotypes. Ten years ago, the most common infections and cancers associated with HPV could be prevented by immunisation with 2vaccines, one bivalent, and another tetravalent, and having just marketed a nonavalent one. During the period 2007-2008, the HPV vaccine was included in the Autonomous Communities vaccination calendar, and it is the second vaccine, after that of Hepatitis B, that prevents cancer. In these 10 years that these vaccines have been available the knowledge has progressed and there have been significant advances in vaccination strategies, as well as in the indications and recommendations. These include, lowering the age in the vaccination schedule, prescribing of 2doses at 9 years and at 13-14 years, systematic vaccination of the male in some countries, immunisation of the woman after adolescence, implementation of vaccination programmes in developed countries, prevention of other cancers, recommendations for vaccinations for populations at high risk of HPV infection, scientific evidence on the impact and effectiveness of vaccination, and confirmation of the safety of these vaccines, with more than 270 million doses administered, as has already been observed in clinical trials. The role of health professionals is essential to achieve and maintain high vaccine coverage. Copyright © 2017 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Next Generation Immunotherapy for Pancreatic Cancer: DNA Vaccination is Seeking New Combo Partners

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Paola Cappello

2018-02-01

Full Text Available Pancreatic Ductal Adenocarcinoma (PDA is an almost incurable radio- and chemo-resistant tumor, and its microenvironment is characterized by a strong desmoplastic reaction associated with a significant infiltration of T regulatory lymphocytes and myeloid-derived suppressor cells (Tregs, MDSC. Investigating immunological targets has identified a number of metabolic and cytoskeletal related molecules, which are typically recognized by circulating antibodies. Among these molecules we have investigated alpha-enolase (ENO1, a glycolytic enzyme that also acts a plasminogen receptor. ENO1 is also recognized by T cells in PDA patients, so we developed a DNA vaccine that targets ENO1. This efficiently induces many immunological processes (antibody formation and complement-dependent cytotoxicity (CDC-mediated tumor killing, infiltration of effector T cells, reduction of infiltration of myeloid and Treg suppressor cells, which significantly increase the survival of genetically engineered mice that spontaneously develop pancreatic cancer. Although promising, the ENO1 DNA vaccine does not completely eradicate the tumor, which, after an initial growth inhibition, returns to proliferate again, especially when Tregs and MDSC ensue in the tumor mass. This led us to develop possible strategies for combinatorial treatments aimed to broaden and sustain the antitumor immune response elicited by DNA vaccination. Based on the data we have obtained in recent years, this review will discuss the biological bases of possible combinatorial treatments (chemotherapy, PI3K inhibitors, tumor-associated macrophages, ENO1 inhibitors that could be effective in amplifying the response induced by the immune vaccination in PDA.

HIV vaccine development: would more (public) money bring quicker results?

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Winsbury, R

1999-01-01

Globally, $200-250 million/year are devoted to HIV vaccine research. Most of those funds pay for basic research rather than product development. Moreover, most of the funds are aimed at the HIV strain commonly found in the US and Europe, and not at the strains common to Africa and other developing countries. While US President Bill Clinton set in 1997 a 10-year target for the development of an HIV vaccine, that target date is looking increasingly unlikely. International vaccine and pharmaceutical companies typically drive vaccine research and development. However, concern over the ultimate profitability of developing and marketing an HIV vaccine, and the fear of major litigation should an eventual vaccine go awry have caused such firms to shy away from investing large amounts of money into HIV vaccine development. These companies somehow have to be attracted back into the field. A World Bank special task force is slated to present its report by mid-1999 on possible funding mechanisms to promote HIV vaccine development. It remains to be resolved whether public funds could and should be used, perhaps through a pooled international vaccine development fund. 2 new International AIDS Vaccine Initiative projects are described.

Successes and failures in human tuberculosis vaccine development.

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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.

A qualitative analysis of South African women's knowledge, attitudes, and beliefs about HPV and cervical cancer prevention, vaccine awareness and acceptance, and maternal-child communication about sexual health.

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Francis, Shelley A; Battle-Fisher, Michele; Liverpool, Joan; Hipple, Lauren; Mosavel, Maghboehba; Soogun, Soji; Mofammere, Nokuthula

2011-11-03

In South Africa, cervical cancer is the second leading cause of death among women. Black South Africa women are disproportionately affected by cervical cancer and have one of the highest mortality rates from this disease. Although the body of literature that examines HPV and cervical cancer prevention is growing in the developing world; there is still a need for a better understanding of women's knowledge and beliefs around HPV and cervical cancer prevention. Therefore, this formative study sought to examine women's attitudes, beliefs and knowledge of HPV and cervical cancer, HPV vaccine acceptance, maternal-child communication about sexuality, and healthcare decision-making and gender roles within an urban community in South Africa. Women ages 18-44 were recruited from an antenatal clinic in a Black township outside of Johannesburg during the fall of 2008. Twenty-four women participated in three focus groups. Findings indicated that the women talked to their children about a variety of sexual health issues; had limited knowledge about HPV, cervical cancer, and the HPV vaccine. Women were interested in learning more about the vaccine although they had reservations about the long-term affect; they reinforced that grandmothers played a key role in a mother's decisions' about her child's health, and supported the idea that government should provide the HPV vaccine as part of the country's immunization program. Our findings indicate the need to develop primary prevention strategies and materials that will provide women with basic cervical cancer prevention messages, including information about HPV, cervical cancer, the HPV vaccine, screening, and how to talk to their children about these topics. Prevention strategies should also consider the cultural context and the role that grandmothers play in the family unit. Copyright © 2011 Elsevier Ltd. All rights reserved.

Knowledge, attitudes, practices and willingness to vaccinate in preparation for the introduction of HPV vaccines in Bamako, Mali

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Tounkara, Karamoko; Rochas, Mali; Beseme, Sarah; Yekta, Shahla; Diallo, Fanta Siby; Tracy, J. Kathleen; Teguete, Ibrahima; Koita, Ousmane A.

2017-01-01

Although screening for pre-cancerous cervical lesions and human papilloma virus (HPV) vaccination are accepted and effective means to prevent cervical cancer, women in Mali have limited access to these interventions. In addition, cervical cancer prevention by HPV vaccination has been controversial in some settings. To reduce cervical cancer prevalence and increase HPV vaccine uptake, it is important to understand the level of knowledge about cervical cancer screening and practices related to vaccination in at-risk populations. In this study, the level of knowledge about HPV and cervical cancer and attitudes towards vaccination were assessed among 301 participants (male and female, adults and adolescents) in a house-to-house survey in two urban neighborhoods in Bamako, Mali. The survey was combined with a brief educational session on HPV. Prior to the education session, overall knowledge of HPV infection and cervical cancer was very low: only 8% knew that HPV is a sexually transmitted infection (STI). Less than 20% of women had ever consulted a gynecologist and less than 3% had ever had cervical cancer screening. After hearing a description of HPV vaccine, more than 80% would accept HPV vaccination; fathers and husbands were identified as primary decisions makers and local clinics or the home as preferred sites for vaccination. This study provides information on STI knowledge and vaccine acceptance in Bamako, Mali in 2012, prior to the introduction of HPV vaccination. PMID:28192460

Knowledge, attitudes, practices and willingness to vaccinate in preparation for the introduction of HPV vaccines in Bamako, Mali.

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Anne S De Groot

Full Text Available Although screening for pre-cancerous cervical lesions and human papilloma virus (HPV vaccination are accepted and effective means to prevent cervical cancer, women in Mali have limited access to these interventions. In addition, cervical cancer prevention by HPV vaccination has been controversial in some settings. To reduce cervical cancer prevalence and increase HPV vaccine uptake, it is important to understand the level of knowledge about cervical cancer screening and practices related to vaccination in at-risk populations. In this study, the level of knowledge about HPV and cervical cancer and attitudes towards vaccination were assessed among 301 participants (male and female, adults and adolescents in a house-to-house survey in two urban neighborhoods in Bamako, Mali. The survey was combined with a brief educational session on HPV. Prior to the education session, overall knowledge of HPV infection and cervical cancer was very low: only 8% knew that HPV is a sexually transmitted infection (STI. Less than 20% of women had ever consulted a gynecologist and less than 3% had ever had cervical cancer screening. After hearing a description of HPV vaccine, more than 80% would accept HPV vaccination; fathers and husbands were identified as primary decisions makers and local clinics or the home as preferred sites for vaccination. This study provides information on STI knowledge and vaccine acceptance in Bamako, Mali in 2012, prior to the introduction of HPV vaccination.

Maternal Support for Human Papillomavirus Vaccination in Honduras

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Langrish, Sarah M.; Cotton, Deborah J.; Simon, Carol J.

2011-01-01

Abstract Background Cervical cancer is a leading cause of cancer death for women in Latin America, and vaccinating against human papillomavirus (HPV) has the potential to limit this disease. We sought to determine Honduran women's awareness of HPV vaccination and interest in vaccinating their daughters against HPV. Methods We interviewed mothers aged ≥17 at primary care clinics in Honduras. First, we collected demographic information and assessed knowledge related to cervical cancer prevention and awareness of HPV and HPV vaccination. Because most participants were not familiar with HPV, education about the relationships among HPV, sexual activity, and cervical cancer was provided before we asked participants if they would accept HPV vaccination for a 9-year-old daughter. We used multivariable logistic regression to determine predictors of vaccine acceptance. Results We interviewed 632 mothers. Only 13% had heard of HPV vaccination before the interview. After education, 91% would accept HPV vaccination for a 9-year-old daughter. Mothers who intended to vaccinate knew more at baseline about cervical cancer prevention than did those who did not endorse vaccination. Demographic characteristics did not predict vaccine acceptance. Conclusions Few Honduran mothers were aware of HPV or HPV vaccination. However, most Honduran mothers would accept HPV vaccination for their daughters after receiving education about the relationship between HPV infection and cervical cancer. Baseline cervical cancer knowledge was associated with vaccine acceptance. PMID:21091226

miR-125b-1 and miR-378a are predictive biomarkers for the efficacy of vaccine treatment against colorectal cancer.

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Tanaka, Hironori; Hazama, Shoichi; Iida, Michihisa; Tsunedomi, Ryouichi; Takenouchi, Hiroko; Nakajima, Masao; Tokumitsu, Yukio; Kanekiyo, Shinsuke; Shindo, Yoshitaro; Tomochika, Shinobu; Tokuhisa, Yoshihiro; Sakamoto, Kazuhiko; Suzuki, Nobuaki; Takeda, Shigeru; Yamamoto, Shigeru; Yoshino, Shigefumi; Ueno, Tomio; Hamamoto, Yoshihiko; Fujita, Yusuke; Tanaka, Hiroaki; Tahara, Ko; Shimizu, Ryoichi; Okuno, Kiyotaka; Fujita, Koji; Kuroda, Masahiko; Nakamura, Yusuke; Nagano, Hiroaki

2017-11-01

Many clinical trials of peptide vaccines have been conducted. However, these vaccines have provided clinical benefits in only a small fraction of patients. The purpose of the present study was to explore microRNAs (miRNAs) as novel predictive biomarkers for the efficacy of vaccine treatment against colorectal cancer. First, we carried out microarray analysis of pretreatment cancer tissues in a phase I study, in which peptide vaccines alone were given. Candidate miRNAs were selected by comparison of the better prognosis group with the poorer prognosis group. Next, we conducted microarray analysis of cancer tissues in a phase II study, in which peptide vaccines combined with chemotherapy were given. Candidate miRNAs were further selected by a similar comparison of prognosis. Subsequently, we carried out reverse-transcription PCR analysis of phase II cases, separating cancer tissues into cancer cells and stromal tissue using laser capture microdissection. Treatment effect in relation to overall survival (OS) and miRNA expression was analyzed. Three miRNA predictors were negatively associated with OS: miR-125b-1 in cancer cells (P = 0.040), and miR-378a in both cancer cells (P = 0.009) and stromal cells (P colorectal cancer. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Synopsis of the 6th Walker's Cay Colloquium on Cancer Vaccines and Immunotherapy

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Marincola Francesco M

2004-06-01

Full Text Available Abstract The 6th annual Cancer Vaccines and Immunotherapy Colloquium at Walker's Cay was held under the auspices of the Albert B. Sabin Vaccine Institute on March 10–13, 2004. The Colloquium consisted of a select group of 34 scientists representing academia, biotechnology and pharmaceutical industry. The main goal of this gathering was to promote in a peaceful and comfortable environment exchanges between basic and clinical science. The secondary benefit was to inspire novel bench to bedside ventures and at the same time provide feed back about promising and/or disappointing clinical results that could help re-frame some scientific question or guide the design of future trials. Several topics were covered that included tumor antigen discovery and validation, platforms for vaccine development, tolerance, immune suppression and tumor escape mechanisms, adoptive T cell therapy and dendritic cell-based therapies, clinical trials and assessment of response. Here we report salient points raised by speakers or by the audience during animated discussion that followed each individual presentation.

Cytotoxic T lymphocyte response to peptide vaccination predicts survival in stage III colorectal cancer.

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Kawamura, Junichiro; Sugiura, Fumiaki; Sukegawa, Yasushi; Yoshioka, Yasumasa; Hida, Jin-Ichi; Hazama, Shoichi; Okuno, Kiyotaka

2018-02-23

We previously reported a phase I clinical trial of a peptide vaccine ring finger protein 43 (RNF43) and 34-kDa translocase of the outer mitochondrial membrane (TOMM34) combined with uracil-tegafur (UFT)/LV for patients with metastatic colorectal cancer (CRC), and demonstrated the safety and immunological responsiveness of this combination therapy. In this study, we evaluated vaccination-induced immune responses to clarify the survival benefit of the combination therapy as adjuvant treatment. We enrolled 44 patients initially in an HLA-masked fashion. After the disclosure of HLA, 28 patients were in the HLA-A*2402-matched and 16 were in the unmatched group. In the HLA-matched group, 14 patients had positive CTL responses specific for the RNF43 and/or TOMM34 peptides after 2 cycles of treatment and 9 had negative responses; in the HLA-unmatched group, 10 CTL responses were positive and 2 negative. In the HLA-matched group, 3-year relapse-free survival (RFS) was significantly better in the positive CTL subgroup than in the negative-response subgroup. Patients with negative vaccination-induced CTL responses showed a significant trend towards shorter RFS than those with positive responses. Moreover, in the HLA-unmatched group, the positive CTL response subgroup showed an equally good 3-year RFS as in the HLA-matched group. In conclusion, vaccination-induced CTL response to peptide vaccination could predict survival in the adjuvant setting for stage III CRC. © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

A vaccine strategy with multiple prostatic acid phosphatase-fused cytokines for prostate cancer treatment.

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Fujio, Kei; Watanabe, Masami; Ueki, Hideo; Li, Shun-Ai; Kinoshita, Rie; Ochiai, Kazuhiko; Futami, Junichiro; Watanabe, Toyohiko; Nasu, Yasutomo; Kumon, Hiromi

2015-04-01

Immunotherapy is one of the attractive treatment strategies for advanced prostate cancer. The US Food and Drug Administration (FDA) previously approved the therapeutic vaccine, sipuleucel-T, which is composed of autologous antigen-presenting cells cultured with a fusion protein [prostatic acid phosphatase (PAP) and granulocyte-macrophage colony-stimulating factor (GMCSF)]. Although sipuleucel-T has been shown to prolong the median survival of patients for 4.1 months, more robust therapeutic effects may be expected by modifying the vaccination protocol. In the present study, we aimed to develop and validate a novel vaccination strategy using multiple PAP-fused cytokines for prostate cancer treatment. Using a super gene expression (SGE) system that we previously established to amplify the production of a recombinant protein, significant amounts of PAP-fused cytokines [human GMCSF, interleukin-2 (IL2), IL4, IL7 and mouse GMCSF and IL4] were obtained. We examined the activity of the fusion proteins in vitro to validate their cytokine functions. A significant upregulation of dendritic cell differentiation from monocytes was achieved by PAP-GMCSF when used with the other PAP-fused cytokines. The PAP-fused human IL2 significantly increased the proliferation of lymphocytes, as determined by flow cytometry. We also investigated the in vivo therapeutic effects of multiple PAP-fused cytokines in a mouse prostate cancer model bearing prostate-specific antigen (PSA)- and PAP-expressing tumors. The simultaneous intraperitoneal administration of PAP-GMCSF, -IL2, -IL4 and -IL7 significantly prevented tumor induction and inhibited the tumor growth in the PAP-expressing tumors, yet not in the PSA-expressing tumors. The in vivo therapeutic effects with the multiple PAP-fused cytokines were superior to the effects of PAP-GMCSF alone. We thus demonstrated the advantages of the combined use of multiple PAP-fused cytokines including PAP-GMCSF, and propose a promising prostatic

Synergistic immuno photothermal nanotherapy (SYMPHONY) to treat unresectable and metastatic cancers and produce and cancer vaccine effect

Science.gov (United States)

Vo-Dinh, Tuan; Inman, Brant; Maccarini, Paolo; Palmer, Gregory; Liu, Yang

2018-02-01

Biocompatible gold nanostars (GNS) with tip-enhanced electromagnetic and optical properties have been developed and applied for multifunctional cancer diagnostics and therapy (theranostics). Their multiple sharp branches acting like "lightning rods" can convert safely and efficiently light into heat. As with other nanoparticles, GNS sizes can be controlled so that they passively accumulate in tumors due to the enhanced permeability and retention (EPR) effect of tumor vasculature. This feature improves tumor-targeting precision and permits the use of reduced laser energy required to destroy the targeted cancer cells. The ability to selectively heat tumor areas where GNS are located while keeping surrounding healthy tissues at significantly lower temperatures offers significant advantages over other thermal therapies. GNS-mediated photothermal therapy combined with checkpoint immunotherapy was shown to reverse tumor-mediated immunosuppression, leading to the treatment of not only primary tumors but also cancer metastasis as well as inducing effective long-lasting immunity, i.e. an anticancer `vaccine' effect.

Mapping HPV Vaccination and Cervical Cancer Screening Practice in the Pacific Region-Strengthening National and Regional Cervical Cancer Prevention

DEFF Research Database (Denmark)

Obel, J; McKenzie, J; Buenconsejo-Lum, L E

2015-01-01

OBJECTIVE: To provide background information for strengthening cervical cancer prevention in the Pacific by mapping current human papillomavirus (HPV) vaccination and cervical cancer screening practices, as well as intent and barriers to the introduction and maintenance of national HPV vaccinatio...... of prevention programs, operational research and advocacy could strengthen political momentum for cervical cancer prevention and avoid risking the lives of many women in the Pacific....

Modeling human papillomavirus and cervical cancer in the United States for analyses of screening and vaccination

Directory of Open Access Journals (Sweden)

Ortendahl Jesse

2007-10-01

Full Text Available Abstract Background To provide quantitative insight into current U.S. policy choices for cervical cancer prevention, we developed a model of human papillomavirus (HPV and cervical cancer, explicitly incorporating uncertainty about the natural history of disease. Methods We developed a stochastic microsimulation of cervical cancer that distinguishes different HPV types by their incidence, clearance, persistence, and progression. Input parameter sets were sampled randomly from uniform distributions, and simulations undertaken with each set. Through systematic reviews and formal data synthesis, we established multiple epidemiologic targets for model calibration, including age-specific prevalence of HPV by type, age-specific prevalence of cervical intraepithelial neoplasia (CIN, HPV type distribution within CIN and cancer, and age-specific cancer incidence. For each set of sampled input parameters, likelihood-based goodness-of-fit (GOF scores were computed based on comparisons between model-predicted outcomes and calibration targets. Using 50 randomly resampled, good-fitting parameter sets, we assessed the external consistency and face validity of the model, comparing predicted screening outcomes to independent data. To illustrate the advantage of this approach in reflecting parameter uncertainty, we used the 50 sets to project the distribution of health outcomes in U.S. women under different cervical cancer prevention strategies. Results Approximately 200 good-fitting parameter sets were identified from 1,000,000 simulated sets. Modeled screening outcomes were externally consistent with results from multiple independent data sources. Based on 50 good-fitting parameter sets, the expected reductions in lifetime risk of cancer with annual or biennial screening were 76% (range across 50 sets: 69–82% and 69% (60–77%, respectively. The reduction from vaccination alone was 75%, although it ranged from 60% to 88%, reflecting considerable parameter

Changes in cytokine and biomarker blood levels in patients with colorectal cancer during dendritic cell-based vaccination

DEFF Research Database (Denmark)

Burgdorf, Stefan K; Claesson, Mogens Helweg; Nielsen, Hans J

2009-01-01

Introduction. Immunotherapy based on dendritic cell vaccination has exciting perspectives for treatment of cancer. In order to clarify immunological mechanisms during vaccination it is essential with intensive monitoring of the responses. This may lead to optimization of treatment and prediction...... of responding patients. The aim of this study was to evaluate cytokine and biomarker responses in patients with colorectal cancer treated with a cancer vaccine based on dendritic cells pulsed with an allogeneic melanoma cell lysate. Material and methods. Plasma and serum samples were collected prior...... disease showed increasing levels of plasma GM-CSF, TNF-alpha, IFN-gamma, IL-2, and IL-5. Patients with progressive disease showed significant increase in CEA and TIMP-1 levels, while patients with stable disease showed relatively unaltered levels. Conclusion. The increased levels of key pro...

Integration of human papillomavirus vaccination and cervical cancer screening in Latin America and the Caribbean.

Science.gov (United States)

Franco, Eduardo L; Tsu, Vivien; Herrero, Rolando; Lazcano-Ponce, Eduardo; Hildesheim, Allan; Muñoz, Nubia; Murillo, Raul; Sánchez, Gloria Ines; Andrus, Jon Kim

2008-08-19

Despite substantial efforts to control cervical cancer by screening, most Latin American and Caribbean countries continue to experience incidence rates of this disease that are much higher than those of other Western countries. The implementation of universal human papillomavirus (HPV) vaccination for young adolescent women is the best prospect for changing this situation. Even though there are financial challenges to overcome to implement such a policy, there is broad political support in the region for adopting universal HPV vaccination. The costs of implementing this policy could be largely alleviated by changing cervical cancer control practices that rely on inefficient use of resources presently allocated to cytology screening. In view of the strong evidence base concerning cervical cancer prevention technologies in the region and the expected impact of vaccination on the performance of cytology, we propose a reformulation of cervical cancer screening policies to be based on HPV testing using validated methods followed by cytologic triage. This approach would serve as the central component of a system that plays the dual role of providing screening and surveillance as integrated and complementary activities sharing centralized resources and coordination.

Genetically modified vaccines augment the efficacy of cancer surgery and chemotherapy

Czech Academy of Sciences Publication Activity Database

Bubeník, Jan

2009-01-01

Roč. 55, č. 6 (2009), s. 199-200 ISSN 0015-5500 Institutional research plan: CEZ:AV0Z50520514 Keywords : genetically modified vaccines * cancer surgery and chemotherapy Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.924, year: 2009

Frederick National Laboratory Rallies to Meet Demand for Zika Vaccine | Frederick National Laboratory for Cancer Research

Science.gov (United States)

The Frederick National Laboratory for Cancer Research is producing another round of Zika vaccine for ongoing studies to determine the best delivery method and dosage. This will lay the groundwork for additional tests to see if the vaccine prevents i

Varicella and herpes zoster vaccine development: lessons learned.

Science.gov (United States)

Warren-Gash, Charlotte; Forbes, Harriet; Breuer, Judith

2017-12-01

Before vaccination, varicella zoster virus (VZV), which is endemic worldwide, led to almost universal infection. This neurotropic virus persists lifelong by establishing latency in sensory ganglia, where its reactivation is controlled by VZV-specific T-cell immunity. Lifetime risk of VZV reactivation (zoster) is around 30%. Vaccine development was galvanised by the economic and societal burden of VZV, including debilitating zoster complications that largely affect older individuals. Areas covered: We describe the story of development, licensing and implementation of live attenuated vaccines against varicella and zoster. We consider the complex backdrop of VZV virology, pathogenesis and immune responses in the absence of suitable animal models and examine the changing epidemiology of VZV disease. We review the vaccines' efficacy, safety, effectiveness and coverage using evidence from trials, observational studies from large routine health datasets and clinical post-marketing surveillance studies and outline newer developments in subunit and inactivated vaccines. Expert commentary: Safe and effective, varicella and zoster vaccines have already made major inroads into reducing the burden of VZV disease globally. As these live vaccines have the potential to reactivate and cause clinical disease, developing alternatives that do not establish latency is an attractive prospect but will require better understanding of latency mechanisms.

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

Current therapeutic vaccination and immunotherapy strategies for HPV-related diseases.

Science.gov (United States)

Skeate, Joseph G; Woodham, Andrew W; Einstein, Mark H; Da Silva, Diane M; Kast, W Martin

2016-06-02

Carcinomas of the anogenital tract, in particular cervical cancer, remains one of the most common cancers in women, and represent the most frequent gynecological malignancies and the fourth leading cause of cancer death in women worldwide. Human papillomavirus (HPV)-induced lesions are immunologically distinct in that they express viral antigens, which are necessary to maintain the cancerous phenotype. The causal relationship between HPV infection and anogenital cancer has prompted substantial interest in the development of therapeutic vaccines against high-risk HPV types targeting the viral oncoproteins E6 and E7. This review will focus on the most recent clinical trials for immunotherapies for mucosal HPV-induced lesions as well as emerging therapeutic strategies that have been tested in pre-clinical models for HPV-induced diseases. Progress in peptide- and protein-based vaccines, DNA-based vaccines, viral/bacterial vector-based vaccines, immune checkpoint inhibition, immune response modifiers, and adoptive cell therapy for HPV will be discussed.

Potential Target Antigens for a Universal Vaccine in Epithelial Ovarian Cancer

NARCIS (Netherlands)

Vermeij, R.; Daemen, T.; de Bock, G.H.; de Graeff, P.; Leffers, N.; Lambeck, A.; Ten Hoor, K.A.; Hollema, H.; van der Zee, A.G.J.; Nijman, H.W.

2010-01-01

The prognosis of epithelial ovarian cancer (EOC), the primary cause of death from gynaecological malignancies, has only modestly improved over the last decades. Immunotherapeutic treatment using a cocktail of antigens has been proposed as a "universal" vaccine strategy. We determined the expression

Mesenchymal stem cells as a novel vaccine platform

Directory of Open Access Journals (Sweden)

Suzanne L. Tomchuck

2012-11-01

Full Text Available Vaccines are the most efficient and cost-effective means of preventing infectious disease. However, traditional vaccine approaches have thus far failed to provide protection against human immunodeficiency virus (HIV, tuberculosis, malaria and many other diseases. New approaches to vaccine development are needed to address some of these intractable problems. In this report, we review the literature identifying stimulatory effects of mesenchymal stem cells (MSC on immune responses and explore the potential for MSC as a novel, universal vaccination platform. MSC are unique bone marrow-derived multipotent progenitor cells that are presently being exploited as gene therapy vectors for a variety of conditions, including cancer and autoimmune diseases. Although MSC are predominantly known for anti-inflammatory properties during allogeneic MSC transplant, there is evidence that MSC can actually promote adaptive immunity under certain settings. MSC have also demonstrated some success in anti-cancer therapeutic vaccines and anti-microbial prophylactic vaccines, as we report, for the first time, the ability of modified MSC to express and secrete a viral antigen that stimulates antigen-specific antibody production in vivo. We hypothesize that the unique properties of modified MSC may enable MSC to serve as an unconventional but innovative, vaccine platform. Such a platform would be capable of expressing hundreds of proteins, thereby generating a broad array of epitopes with correct post-translational processing, mimicking natural infection. By stimulating immunity to a combination of epitopes, it may be possible to develop prophylactic and even therapeutic vaccines to tackle major health problems including those of non-microbial and microbial origin, including cancer, or an infectious disease like HIV, where traditional vaccination approaches have failed.

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.

Towards the eradication of HPV infection through universal specific vaccination

OpenAIRE

Crosignani, Piergiorgio; De Stefani, Antonella; Fara, Gaetano Maria; Isidori, Andrea M; Lenzi, Andrea; Liverani, Carlo Antonio; Lombardi, Alberto; Mennini, Francesco Saverio; Palu?, Giorgio; Pecorelli, Sergio; Peracino, Andrea P; Signorelli, Carlo; Zuccotti, Gian Vincenzo

2013-01-01

Background The Human Papillomavirus (HPV) is generally recognized to be the direct cause of cervical cancer. The development of effective anti-HPV vaccines, included in the portfolio of recommended vaccinations for any given community, led to the consolidation in many countries of immunization programs to prevent HPV-related cervical cancers. In recent years, increasing evidence in epidemiology and molecular biology have supported the oncogenic role of HPV in the development of other neoplasm...

Tumor Radiation Therapy Creates Therapeutic Vaccine Responses to the Colorectal Cancer Antigen GUCY2C

Energy Technology Data Exchange (ETDEWEB)

Witek, Matthew [Department of Radiation Oncology, Kimmel Cancer Center, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Blomain, Erik S.; Magee, Michael S.; Xiang, Bo; Waldman, Scott A. [Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Snook, Adam E., E-mail: adam.snook@jefferson.edu [Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, Pennsylvania (United States)

2014-04-01

Purpose: Radiation therapy (RT) is thought to produce clinical responses in cancer patients, not only through direct toxicity to cancer cells and supporting tumor stroma cells, but also through activation of immunologic effectors. More recently, RT has potentiated the local and systemic effects of cancer immunotherapy (IT). However, combination regimens that maximize immunologic and clinical efficacy remain undefined. Methods and Materials: We evaluated the impact of local RT on adenoviral-mediated vaccination against the colorectal cancer antigen GUCY2C (Ad5-GUCY2C) in a murine subcutaneous tumor model using mouse CT26 colon cancer cells (CT26-GUCY2C). Immune responses were assessed by ELISpot, and clinical responses were assessed by tumor size and incidence. Results: The specific sequence of tumor-directed RT preceding Ad5-GUCY2C IT transformed inactive therapeutic Ad5-GUCY2C vaccination into a curative vaccine. GUCY2C-specific T cell responses were amplified (P<.05), tumor eradication was maximized (P<.01), and tumor volumes were minimized (P<.001) in mice whose tumors were irradiated before, compared with after, Ad5-GUCY2C vaccination. The immunologic and antitumor efficacy of Ad5-GUCY2C was amplified comparably by unfractionated (8 Gy × 1), or biologically equivalent doses of fractionated (3.5 Gy × 3), RT. The antitumor effects of sequential RT and IT (RT-IT) depended on expression of GUCY2C by tumor cells and the adenoviral vaccine vector, and tumor volumes were inversely related to the magnitude of GUCY2C-specific T cell responses. Moreover, mice cured of CT26-GUCY2C tumors by RT-IT showed long-lasting antigen-dependent protection, resisting tumors formed by GUCY2C-expressing 4T1 breast cancer cells inoculated 50 days after CT26 cells. Conclusions: Optimal sequencing of RT and IT amplifies antigen-specific local and systemic immune responses, revealing novel acute and long-term therapeutic antitumor protection. These observations underscore the importance

Cancer Vaccines: State of the Art of the Computational Modeling Approaches

Directory of Open Access Journals (Sweden)

Francesco Pappalardo

2013-01-01

Full Text Available Cancer vaccines are a real application of the extensive knowledge of immunology to the field of oncology. Tumors are dynamic complex systems in which several entities, events, and conditions interact among them resulting in growth, invasion, and metastases. The immune system includes many cells and molecules that cooperatively act to protect the host organism from foreign agents. Interactions between the immune system and the tumor mass include a huge number of biological factors. Testing of some cancer vaccine features, such as the best conditions for vaccine administration or the identification of candidate antigenic stimuli, can be very difficult or even impossible only through experiments with biological models simply because a high number of variables need to be considered at the same time. This is where computational models, and, to this extent, immunoinformatics, can prove handy as they have shown to be able to reproduce enough biological complexity to be of use in suggesting new experiments. Indeed, computational models can be used in addition to biological models. We now experience that biologists and medical doctors are progressively convinced that modeling can be of great help in understanding experimental results and planning new experiments. This will boost this research in the future.

Next-Generation Dengue Vaccines: Novel Strategies Currently Under Development

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Anna P. Durbin

2011-09-01

Full Text Available Dengue has become the most important arboviral infection worldwide with more than 30 million cases of dengue fever estimated to occur each year. The need for a dengue vaccine is great and several live attenuated dengue candidate vaccines are proceeding through clinical evaluation. The need to induce a balanced immune response against all four DENV serotypes with a single vaccine has been a challenge for dengue vaccine developers. A live attenuated DENV chimeric vaccine produced by Sanofi Pasteur has recently entered Phase III evaluation in numerous dengue-endemic regions of the world. Viral interference between serotypes contained in live vaccines has required up to three doses of the vaccine be given over a 12-month period of time. For this reason, novel DENV candidate vaccines are being developed with the goal of achieving a protective immune response with an immunization schedule that can be given over the course of a few months. These next-generation candidates include DNA vaccines, recombinant adenovirus vectored vaccines, alphavirus replicons, and sub-unit protein vaccines. Several of these novel candidates will be discussed.

Next-generation dengue vaccines: novel strategies currently under development.

Science.gov (United States)

Durbin, Anna P; Whitehead, Stephen S

2011-10-01

Dengue has become the most important arboviral infection worldwide with more than 30 million cases of dengue fever estimated to occur each year. The need for a dengue vaccine is great and several live attenuated dengue candidate vaccines are proceeding through clinical evaluation. The need to induce a balanced immune response against all four DENV serotypes with a single vaccine has been a challenge for dengue vaccine developers. A live attenuated DENV chimeric vaccine produced by Sanofi Pasteur has recently entered Phase III evaluation in numerous dengue-endemic regions of the world. Viral interference between serotypes contained in live vaccines has required up to three doses of the vaccine be given over a 12-month period of time. For this reason, novel DENV candidate vaccines are being developed with the goal of achieving a protective immune response with an immunization schedule that can be given over the course of a few months. These next-generation candidates include DNA vaccines, recombinant adenovirus vectored vaccines, alphavirus replicons, and sub-unit protein vaccines. Several of these novel candidates will be discussed.

Safety and preliminary evidence of biologic efficacy of a mammaglobin-a DNA vaccine in patients with stable metastatic breast cancer.

Science.gov (United States)

Tiriveedhi, Venkataswarup; Tucker, Natalia; Herndon, John; Li, Lijin; Sturmoski, Mark; Ellis, Matthew; Ma, Cynthia; Naughton, Michael; Lockhart, A Craig; Gao, Feng; Fleming, Timothy; Goedegebuure, Peter; Mohanakumar, Thalachallour; Gillanders, William E

2014-12-01

Mammaglobin-A (MAM-A) is overexpressed in 40% to 80% of primary breast cancers. We initiated a phase I clinical trial of a MAM-A DNA vaccine to evaluate its safety and biologic efficacy. Patients with breast cancer with stable metastatic disease were eligible for enrollment. Safety was monitored with clinical and laboratory assessments. The CD8 T-cell response was measured by ELISPOT, flow cytometry, and cytotoxicity assays. Progression-free survival (PFS) was described using the Kaplan-Meier product limit estimator. Fourteen subjects have been treated with the MAM-A DNA vaccine and no significant adverse events have been observed. Eight of 14 subjects were HLA-A2(+), and the CD8 T-cell response to vaccination was studied in detail. Flow cytometry demonstrated a significant increase in the frequency of MAM-A-specific CD8 T cells after vaccination (0.9% ± 0.5% vs. 3.8% ± 1.2%; P cells (41 ± 32 vs. 215 ± 67 spm; P cell responses, and preliminary evidence suggests improved PFS. Additional studies are required to define the potential of the MAM-A DNA vaccine for breast cancer prevention and/or therapy. ©2014 American Association for Cancer Research.

Formulation of the bivalent prostate cancer vaccine with surgifoam elicits antigen-specific effector T cells in PSA-transgenic mice.

Science.gov (United States)

Karan, Dev

2017-10-13

We previously developed and characterized an adenoviral-based prostate cancer vaccine for simultaneous targeting of prostate-specific antigen (PSA) and prostate stem cell antigen (PSCA). We also demonstrated that immunization of mice with the bivalent vaccine (Ad 5 -PSA+PSCA) inhibited the growth of established prostate tumors. However, there are multiple challenges hindering the success of immunological therapies in the clinic. One of the prime concerns has been to overcome the immunological tolerance and maintenance of long-term effector T cells. In this study, we further characterized the use of the bivalent vaccine (Ad 5 -PSA+PSCA) in a transgenic mouse model expressing human PSA in the mouse prostate. We demonstrated the expression of PSA analyzed at the mRNA level (by RT-PCR) and protein level (by immunohistochemistry) in the prostate lobes harvested from the PSA-transgenic (PSA-Tg) mice. We established that the administration of the bivalent vaccine in surgifoam to the PSA-Tg mice induces strong PSA-specific effector CD8 + T cells as measured by IFN-γ secretion and in vitro cytotoxic T-cell assay. Furthermore, the use of surgifoam with Ad 5 -PSA+PSCA vaccine allows multiple boosting vaccinations with a significant increase in antigen-specific CD8 + T cells. These observations suggest that the formulation of the bivalent prostate cancer vaccine (Ad 5 -PSA+PSCA) with surgifoam bypasses the neutralizing antibody response, thus allowing multiple boosting. This formulation is also helpful for inducing an antigen-specific immune response in the presence of self-antigen, and maintains long-term effector CD8 + T cells. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Depletion of Treg cells augments the therapeutic effect of cancer vaccines

Czech Academy of Sciences Publication Activity Database

Bubeník, Jan

2006-01-01

Roč. 52, č. 6 (2006), s. 202-204 ISSN 0015-5500 Grant - others:EU-FP6-Clinigene(XE) 018933 Institutional research plan: CEZ:AV0Z50520514 Keywords : Treg cells * cancer vaccines Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.387, year: 2006

Vaccination with melanoma lysate-pulsed dendritic cells, of patients with advanced colorectal carcinoma: report from a phase I study

DEFF Research Database (Denmark)

Burgdorf, S K; Fischer, A; Claesson, M H

2006-01-01

Immune therapy have shown new and exciting perspectives for cancer treatment. Aim of our study was to evaluate toxicity and possible adverse effects from vaccination of patients with advanced colorectal cancer with autologous dendritic cells (DC) pulsed with lysate from a newly developed melanoma...... contained 3-5 x 10(6) DCs. Five of the six patients received all five vaccines. The treatment was well tolerated in all patients without any observed vaccine-correlated adverse effects. Treatment with this DC-based cancer vaccine proved safe and non-toxic.......Immune therapy have shown new and exciting perspectives for cancer treatment. Aim of our study was to evaluate toxicity and possible adverse effects from vaccination of patients with advanced colorectal cancer with autologous dendritic cells (DC) pulsed with lysate from a newly developed melanoma...... and selected melanoma cell line enriched in expression of MAGE-A antigens and deficient in expression of melanoma differentiation antigens: tyrosinase, MART-1 and gp100. Vaccinations were administered intradermally on the proximal thigh with a total of five given vaccines at 2 weeks intervals. Each vaccine...

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.

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 ...

Human papillomavirus (HPV vaccination for the prevention of HPV 16/18 induced cervical cancer and its precursors

Directory of Open Access Journals (Sweden)

Greiner, Wolfgang

2009-03-01

Full Text Available Introduction: Essential precondition for the development of cervical cancer is a persistent human papillomavirus (HPV infection. The majority - approximately 70% - of cervical carcinomas is caused by two high-risk HPV types (16 and 18. Recently, two vaccines have been approved to the German market with the potential to induce protection against HPV 16 and HPV 18 among additional low-risk virus types. Objectives: To analyse whether HPV vaccination is effective with regard to the reduction of cervical cancer and precursors of cervical carcinoma (CIN, respectively? Does HPV vaccination represent a cost-effective alternative or supplement to present screening practice? Are there any differences concerning cost-effectiveness between the two available vaccines? Should HPV vaccination be recommended from a health economic point of view? If so, which recommendations can be conveyed with respect to a (reorganization of the German vaccination strategy? Which ethical, social and legal implications have to be considered? Methods: Based on a systematic literature review, randomized controlled trials (RCT looking at the effectiveness of HPV vaccination for the prevention of cervical carcinoma and its precursors - cervical intraepithelial neoplasia - have been identified. In addition, health economic models were identified to address the health economic research questions. Quality assessment of medical and economic literature was assured by application of general assessment standards for the systematic and critical appraisal of scientific studies. Results: Vaccine efficacy in prevention of CIN 2 or higher lesions in HPV 16 or HPV 18 negative women, who received all vaccination doses, ranges between 98% and 100%. Side effects of the vaccination are mainly associated with injection site reactions (redness, turgor, pain. No significant differences concerning serious complications between the vaccination- and the placebo-groups were reported. Results of base case

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.

Establishing Correlates of Protection for Vaccine Development: Considerations for the Respiratory Syncytial Virus Vaccine Field.

Science.gov (United States)

Kulkarni, Prasad S; Hurwitz, Julia L; Simões, Eric A F; Piedra, Pedro A

2018-03-01

Correlates of protection (CoPs) can play a significant role in vaccine development by assisting the selection of vaccine candidates for clinical trials, supporting clinical trial design and implementation, and simplifying tests of vaccine modifications. Because of this important role in vaccine development, it is essential that CoPs be defined by well-designed immunogenicity and efficacy studies, with attention paid to benefits and limitations. The respiratory syncytial virus (RSV) field is unique in that a great deal of information about the humoral response is available from basic research and clinical studies. Polyclonal and monoclonal antibodies have been used routinely in the clinic to protect vulnerable infants from infection, providing a wealth of information about correlations between neutralizing antibodies and disease prevention. Considerations for the establishment of future CoPs to support RSV vaccine development in different populations are therefore discussed.

Calreticulin as cancer treatment adjuvant: combination with photodynamic therapy and photodynamic therapy-generated vaccines

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Mladen eKorbelik

2015-02-01

Full Text Available Calreticulin is recognized as one of pivotal damage-associated molecular pattern (DAMP molecules alerting the host of the presence of distressed cells. In this role, calreticulin becomes exposed on the surface of tumor cells treated by several types of cancer therapy including photodynamic therapy (PDT. The goal of the present study was to examine the potential of externally added calreticulin for augmenting antitumor effect mediated by PDT. Recombinant calreticulin was found to bind to mouse SCCVII tumor cells treated by PDT. Compared to the outcome with PDT alone, cure-rates of SCCVII tumors grown in immunocompetent C3H/HeN mice were elevated when calreticulin (0.4 mg/mouse was injected peritumorally immediately after PDT. Such therapeutic gain with PDT plus calreticulin combination was not obtained with SCCVII tumors growing in immunodeficient NOD-scid mice. In PDT vaccine protocol, where PDT-treated SCCVII cells are used for vaccination of SCCVII tumor-bearing mice, adding recombinant calreticulin to cells before their injection produced improved therapeutic effect. The expression of calreticulin gene was reduced in PDT-treated cells, while no changes were observed with the expression of this gene in tumor, liver, and spleen tissues in PDT vaccine-treated mice. These findings reveal that externally added recombinant calreticulin can boost antitumor responses elicited by PDT or PDT-generated vaccines, and can thus serve as an effective adjuvant for cancer treatment with PDT and probably other cancer cell stress-inducing modalities.

Terapeutiske vacciner er et nyt behandlings-princip ved kastrationsresistent prostatacancer

DEFF Research Database (Denmark)

Djurhuus, Sissal Sigmundsdòttir; Brasso, Klaus; Berg, Kasper Drimer

2015-01-01

Therapeutic vaccines is a novel approach in castration-resistant prostate cancer treatment Castration-resistant prostate cancer (CRPC) is defined as tumour progression despite castrate levels of serum testosterone. During the past decade a number of new therapies, including chemo­therapy and novel...... endocrine agents have been approved for CRPC treatment. The continued need for new effective drugs in CRPC has led to development of a novel therapeutic approach in CRPC treatment. Therapeutic vaccines activate the immune system to kill prostate cancer cells. This review describes recent pivotal phase 2...... and 3 trials of CRPC vaccines and discusses the impact on future CRPC management....

Urban-rural inequities in the parental attitudes and beliefs towards Human papillomavirus infection, cervical cancer and HPV vaccine in Mysore, India.

Science.gov (United States)

Degarege, Abraham; Krupp, Karl; Fennie, Kristopher; Li, Tan; Stephens, Dionne P; Marlow, Laura A V; Srinivas, Vijaya; Arun, Anjali; Madhivanan, Purnima

2018-03-26

The aim of this study was to compare the parental attitudes and beliefs about HPV, cervical cancer and HPV vaccine between urban and rural areas, India. Cross sectional SETTING: Mysore, India PARTICIPANTS: Parents of school going adolescent girls INTERVENTION: Parents completed a self-administered questionnaire MAIN OUTCOME MEASURES: : Attitudes and beliefs about HPV, cervical cancer and HPV vaccine RESULTS: A total of 1609 parents from urban (n=778) and rural (n=831) areas participated in this study. Majority of the parents had never heard about HPV (73.6%), did not know that their daughters could get an HPV infection (62.7%) or cervical cancer (64.1%) in the future, and believed that HPV vaccine was not effective (67.1%). Parents living in the urban area were more likely to believe that HPV infection (adjusted Odds Ratio [aOR] 2.69; 95%CI:1.43, 5.06) and cervical cancer (aOR 2.68; 95%CI:1.83, 3.91) could cause serious health problems than those living in the rural area. The odds of agreeing that HPV vaccination will make girls sexually active was lower among urban than rural parents (aOR 0.55; 95%CI:0.33, 0.94). There was no significant difference among parents in the urban and rural areas in their beliefs about susceptibility of their daughter to HPV infection or cervical cancer, and beliefs about the safety and ability of HPV vaccine to protect cervical cancer. Rural parents might be reluctant to recommend behaviors that can help prevent HPV infection and cervical cancer such as HPV vaccination for their daughters. Copyright © 2018. Published by Elsevier Inc.

Vaccines for the 21st century

Science.gov (United States)

Delany, Isabel; Rappuoli, Rino; De Gregorio, Ennio

2014-01-01

In the last century, vaccination has been the most effective medical intervention to reduce death and morbidity caused by infectious diseases. It is believed that vaccines save at least 2–3 million lives per year worldwide. Smallpox has been eradicated and polio has almost disappeared worldwide through global vaccine campaigns. Most of the viral and bacterial infections that traditionally affected children have been drastically reduced thanks to national immunization programs in developed countries. However, many diseases are not yet preventable by vaccination, and vaccines have not been fully exploited for target populations such as elderly and pregnant women. This review focuses on the state of the art of recent clinical trials of vaccines for major unmet medical needs such as HIV, malaria, TB, and cancer. In addition, we describe the innovative technologies currently used in vaccine research and development including adjuvants, vectors, nucleic acid vaccines, and structure-based antigen design. The hope is that thanks to these technologies, more diseases will be addressed in the 21st century by novel preventative and therapeutic vaccines. PMID:24803000

Multimodal Counseling Interventions: Effect on Human Papilloma Virus Vaccination Acceptance

OpenAIRE

Oroma Nwanodi; Helen Salisbury; Curtis Bay

2017-01-01

Human papilloma virus (HPV) vaccine was developed to reduce HPV-attributable cancers, external genital warts (EGW), and recurrent respiratory papillomatosis. Adolescent HPV vaccination series completion rates are less than 40% in the United States of America, but up to 80% in Australia and the United Kingdom. Population-based herd immunity requires 80% or greater vaccination series completion rates. Pro-vaccination counseling facilitates increased vaccination rates. Multimodal counseling inte...

Influenza vaccination of cancer patients during PD-1 blockade induces serological protection but may raise the risk for immune-related adverse events.

Science.gov (United States)

Läubli, Heinz; Balmelli, Catharina; Kaufmann, Lukas; Stanczak, Michal; Syedbasha, Mohammedyaseen; Vogt, Dominik; Hertig, Astrid; Müller, Beat; Gautschi, Oliver; Stenner, Frank; Zippelius, Alfred; Egli, Adrian; Rothschild, Sacha I

2018-05-22

Immune checkpoint inhibiting antibodies were introduced into routine clinical practice for cancer patients. Checkpoint blockade has led to durable remissions in some patients, but may also induce immune-related adverse events (irAEs). Lung cancer patients show an increased risk for complications, when infected with influenza viruses. Therefore, vaccination is recommended. However, the efficacy and safety of influenza vaccination during checkpoint blockade and its influence on irAEs is unclear. Similarly, the influence of vaccinations on T cell-mediated immune reactions in patients during PD-1 blockade remains poorly defined. We vaccinated 23 lung cancer patients and 11 age-matched healthy controls using a trivalent inactivated influenza vaccine to investigate vaccine-induced immunity and safety during checkpoint blockade. We did not observe significant differences between patients and healthy controls in vaccine-induced antibody titers against all three viral antigens. Influenza vaccination resulted in protective titers in more than 60% of patients/participants. In cancer patients, the post-vaccine frequency of irAEs was 52.2% with a median time to occurrence of 3.2 months after vaccination. Six of 23 patients (26.1%) showed severe grade 3/4 irAEs. This frequency of irAEs might be higher than the rate previously published in the literature and the rate observed in a non-study population at our institution (all grades 25.5%, grade 3/4 9.8%). Although this is a non-randomized trial with a limited number of patients, the increased rate of immunological toxicity is concerning. This finding should be studied in a larger patient population.

Cost-effectiveness of quadrivalent human papillomavirus vaccination in adolescent girls

Directory of Open Access Journals (Sweden)

A. V. Rudakova

2016-01-01

Full Text Available The human papillomavirus (HPV infection is one of the major risk factor of development of genital warts, a cervical dysplasia, a cervical cancer, and also some other oncologic diseases. The usage of quadrivalent HPV vaccine in girls reduces the corresponding case rate and the mortality significantly.The objective of this study is to analyze the cost-effectiveness of quadrivalent HPV vaccination cases of 12-yearold girls in Russian Federation.Materials and methods. A Markov model is used on the basis of epidemiological data in Russian Federation. The cost-effectiveness was estimated from societal perspective. We assumed that the effect of vaccination remains throughout all life. The analysis is performed for survival of 12-year-old girls. We considered only effect in the vaccinated population. Costs for therapy of the diseases associated with HPV infection corresponded to compulsory health insurance rates across St. Petersburg for 2016. Costs and life expectancy have been discounted for 3,5% a year.Results. Quadrivalent HPV vaccination of 12-year-old girls in Russian Federation will allow to prevent counting on 10000 the vaccinated persons 293 cases of genital warts, 15 cases of pre invasive cervical cancer, 81 cases of invasive cervical cancer, 6 cases of vulvar cancer, 2 cases of vaginal cancer, 2 cases of anal cancer, 1 case of oropharyngeal cancer. In general, 49 cases of death caused by HPV infection on 10000 vaccinated girls would be prevented. The vaccination will provide cost reduction, caused by HPV-associated diseases, for 68% (58,38 million rubles on 10000 vaccinated, and 96% of the predicted prevented costs will be caused by decrease in incidence of cervical cancer. The quadrivalent HPV vaccination is associated with an incremental cost-effectiveness ratio (ICER of 172 000 rubles per quality adjusted life-year (QALY and 411 300 rubles per death caused by HPV-associated diseases.Conclusions. Quadrivalent

Malaria Vaccine Development: The Need for Novel Approach-es: A Review Article

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Shima MAHMOUDI

2018-03-01

Full Text Available Background: Although rigorous efforts have substantially decreased the malaria burden through decades, it still threatens the lives of millions of children. Development of an effective vaccine can provide important approach in malaria control strategies. Unfortunately, development of an effective vaccine for falciparum malaria has been hindered by the extreme complexity of malaria parasite biology, complex and diverse parasite genomes, and immune evasion by the parasites as well as the intricate nature of the parasites infection cycle. The aim of this review was to discuss the different approaches to malaria vaccine development until now.Methods: Scientific databases, including MEDLINE (via PubMed and SCOPUS were searched up to 30 Jan 2017 and the articles regarding malaria vaccine development were taken into examination.Results: Several strategies for malaria vaccine development including pre-erythrocytic vaccines, antibody-based subunit vaccines, vectored vaccines, whole sporozoite vaccines, genetically Attenuated parasites and sporozoite subunit vaccine, erythrocytic vaccines, sexual stage vaccine, transmission-blocking vaccine as well as synthetic peptides and conjugate vaccine has been introduced. However, the success has been limited thus far.Conclusion: Although development of malaria vaccine over the past 70 year has been continued, the discovery, development, and licensing of a malaria vaccine formulation, which meets safety, affordability, accessibility, applicability, and efficacy has not yet been achieved.

Immune Monitoring in Cancer Vaccine Clinical Trials: Critical Issues of Functional Flow Cytometry-Based Assays

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Iole Macchia

2013-01-01

Full Text Available The development of immune monitoring assays is essential to determine the immune responses against tumor-specific antigens (TSAs and tumor-associated antigens (TAAs and their possible correlation with clinical outcome in cancer patients receiving immunotherapies. Despite the wide range of techniques used, to date these assays have not shown consistent results among clinical trials and failed to define surrogate markers of clinical efficacy to antitumor vaccines. Multiparameter flow cytometry- (FCM- based assays combining different phenotypic and functional markers have been developed in the past decade for informative and longitudinal analysis of polyfunctional T-cells. These technologies were designed to address the complexity and functional heterogeneity of cancer biology and cellular immunity and to define biomarkers predicting clinical response to anticancer treatment. So far, there is still a lack of standardization of some of these immunological tests. The aim of this review is to overview the latest technologies for immune monitoring and to highlight critical steps involved in some of the FCM-based cellular immune assays. In particular, our laboratory is focused on melanoma vaccine research and thus our main goal was the validation of a functional multiparameter test (FMT combining different functional and lineage markers to be applied in clinical trials involving patients with melanoma.

Predictors of intent to vaccinate against HPV/cervical cancer: a multi-ethnic survey of 769 parents in New Zealand.

Science.gov (United States)

Rose, Sally B; Lawton, Beverley A; Lanumata, Tolotea S; Hibma, Merilyn; Baker, Michael G

2012-02-24

To identify factors predictive of parents' intent to have their daughters' receive the HPV/cervical cancer vaccine. 3123 questionnaires were distributed to parents recruited from 14 socioeconomically diverse schools in 2008. Survey questions were structured around the health beliefs model. The main outcome measure was intent to seek vaccination for daughter(s). A quarter of parents completed questionnaires (769/3123). Two-thirds of respondents (67%) indicated they would want their daughter(s) to receive the vaccine, with no significant differences by ethnicity. Intent to vaccinate was significantly associated with having fewer negative views on vaccination (OR 0.47, 95%CI 0.37-0.59), having adequate information about the vaccine, perceiving HPV infection and cervical cancer as serious and likely to occur (OR 1.2, 95%CI 1.05-1.36), and considering efficacy and safety of the vaccine important (OR 1.17, 95%CI 1.06-1.28) (pHPV-related facts was lowest among Maori and Pacific parents (pparents were more likely to have concerns about vaccination impacting negatively on girls' sexual behaviour. Strategies will be needed to provide detailed information outlining HPV prevalence and consequences, vaccine safety and efficacy to ensure all parents and their daughters are adequately informed when deciding on vaccination.

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

Development of a Vaccine for Eradicating Contagious Bovine ...

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

Since eventual success depends on the vaccine's acceptability by livestock keepers, the project involves them in field-testing and assesses their willingness to pay for the vaccine. The project also ... Outputs. Studies. Developing vaccines for animals, the case of Contagious Bovine Pleuropneumonia (CBPP) in Africa. 53232.

Promising new developments in cancer chemotherapy.

Science.gov (United States)

Ferrante, K; Winograd, B; Canetta, R

1999-01-01

The positive impact on survival of traditional chemotherapeutic agents has renewed interest in developing newer cytotoxic agents and orally active compounds with improved therapeutic indices. In addition, new insights into the pathways of human tumorigenesis have led to novel approaches aimed at specific mechanism-based targets. The taxane class, of which paclitaxel was the first member, has the unique ability to promote and stabilize microtubule function directly, thereby inhibiting mitotic progression and inducing apoptotic cell death. Paclitaxel provides treatment benefit in a broad range of solid tumors including breast, ovarian, and lung cancer. The success with paclitaxel stimulated interest in the microtubule as a new therapeutic target. Taxane analogues with improved preclinical efficacy have been identified and are entering clinical trials. The enthusiasm for oral anticancer agents and the therapeutic importance of platinum compounds has led to the development of JM216 (satraplatin), a novel platinum IV coordination complex with oral activity in cisplatin-resistant cell lines, which is now in phase III trials in prostate cancer. Another compound in late development is DPPE, a chemopotentiator that enhances the in vivo antitumor effects of cytotoxic agents such as doxorubicin, cyclophosphamide, and cisplatin. Agents that inhibit topoisomerase I and II have also been of interest. TAS-103 is a dual topoisomerase I and II inhibitor with preclinical efficacy in a broad spectrum of tumors and in multidrug-resistant tumor cell lines. Vaccination strategies represent a rational therapeutic approach in the minimal residual disease or high-risk adjuvant therapy setting. The GMK and MGV vaccines utilizing ganglioside antigens overexpressed on human tumors such as melanoma and small cell lung cancer appear to induce antibody production reliably at tolerable doses and are under further clinical investigation. Inhibition of matrix metalloproteinases (MMPs) is another

Phase I clinical study of anti-apoptosis protein, survivin-derived peptide vaccine therapy for patients with advanced or recurrent colorectal cancer

Directory of Open Access Journals (Sweden)

Minamida Hidetoshi

2004-06-01

Full Text Available Abstract Survivin is a member of the inhibitor of apoptosis protein (IAP family containing a single baculovirus IAP repeat domain. It is expressed during fetal development but becomes undetectable in terminally differentiated normal adult tissues. We previously reported that survivin and its splicing variant survivin-2B was expressed abundantly in various types of tumor tissues as well as tumor cell lines and was suitable as a target antigen for active-specific anti-cancer immunization. Subsequently, we identified an HLA-A24-restricted antigenic peptide, survivin-2B80-88 (AYACNTSTL recognized by CD8+ cytotoxic T lymphocytes (CTLs. We, therefore, started a phase I clinical study assessing the efficacy of survivin-2B peptide vaccination in patients with advanced or recurrent colorectal cancer expressing survivin. Vaccinations with survivin-2B peptide were given subcutaneously six times at 14-day intervals. Of 15 patients who finished receiving the vaccination schedule, three suffered slight toxicities, including anemia (grade 2, general malaise (grade 1, and fever (grade 1. No severe adverse events were observed in any patient. In 6 patients, tumor marker levels (CEA and CA19-9 decreased transiently during the period of vaccination. Slight reduction of the tumor volume was observed in one patient, which was considered a minor responder. No changes were noted in three patients while the remaining eleven patients experienced tumor progression. Analysis of peripheral blood lymphocytes of one patient using HLA-A24/peptide tetramers revealed an increase in peptide-specific CTL frequency from 0.09% to 0.35% of CD8+ T cells after 4 vaccinations. This phase I clinical study indicates that survivin-2B peptide-based vaccination is safe and should be further considered for potential immune and clinical efficacy in HLA-A24-expression patients with colorectal cancer.

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

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.

Development and validation of an attenuated Mycoplasma hyopneumoniae aerosol vaccine.

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Feng, Zhi-Xin; Wei, Yan-Na; Li, Gui-Lan; Lu, Xiao-Ming; Wan, Xiu-Feng; Pharr, G Todd; Wang, Zhan-Wei; Kong, Meng; Gan, Yuan; Bai, Fang-Fang; Liu, Mao-Jun; Xiong, Qi-Yan; Wu, Xu-Su; Shao, Guo-Qing

2013-12-27

Mycoplasma hyopneumoniae (M. hyopneumoniae) causes a chronic respiratory disease with high morbidity and low mortality in swine, and has been presented as a major cause of growth retardation in the swine industry. Aerosol vaccination presents a needle free, high throughput, and efficient platform for vaccine delivery, and has been widely applied in poultry vaccination. However, aerosol vaccines have rarely been used in swine vaccination primarily because the long and curving respiratory track of swine presents a barrier for vaccine particle delivery. To develop an effective M. hyopneumoniae aerosol vaccine, three major barriers need to be overcome: to optimize particle size for aerosol delivery, to maintain the viability of mycoplasma cells in the vaccine, and to optimize the environmental conditions for vaccine delivery. In this study, an aerosol mycoplasma vaccine was successfully developed based on a conventional live attenuated M. hyopneumoniae vaccine. Specifically, the Pari LCD nebulizer was used to produce an aerosol vaccine particle size less than 5 μm; and a buffer with 5% glycerol was developed and optimized to prevent inactivation of M. hyopneumoniae caused by aerosolization and evaporation. Before nebulization, the room temperature and relative humidity were control to 20-25 °C and 70-75%, respectively, which helped maintain the viability of aerosol vaccine. Animal experiments demonstrated that this newly developed aerosol vaccine was effectively delivered to swine low respiratory track, being confirmed by nested-PCR, in situ hybridization and scanning electron microscope. Moreover, M. hyopneumoniae specific sIgA secretion was detected in the nasal swab samples at 14 days post-immunization. To our knowledge, this is the first report on a live M. hyopneumoniae aerosol vaccine. Copyright © 2013 Elsevier B.V. All rights reserved.

Perceptions of Nigerian Women about Human Papilloma Virus, Cervical Cancer, and HPV Vaccine

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Olusola Anuoluwapo Akanbi

2015-01-01

Full Text Available Background. Cervical cancer caused by human papilloma virus (HPV though preventable has claimed the lives of many women worldwide. This study was embarked upon to evaluate the general knowledge and perceptions of Nigerian women on HPV, cervical cancer, and HPV vaccine. Methods. Structured questionnaires were administered to a cross section of 737 women randomly selected from the general population in two southwestern States of Nigeria. Statistical analysis was done using SPSS computer software version 16. A P value >0.05 was considered statistically significant. Results. One hundred and seventy-six (23.9% of the respondents had knowledge of HPV; 474 (64.3% are aware of cervical cancer but only 136 (18.5% know that HPV causes cervical cancer. 200 (27.1% are aware that there is an HPV vaccine while 300 (40.7% had knowledge of Pap smear test. Two hundred and sixty (35.3% of the respondents know that early detection of HPV can prevent cervical cancer and in spite of this, only 110 (14.9% have taken the Pap smear test before while 151 (20.5% are not willing to go for the test at all. Conclusions. There is therefore the need to create proper awareness on the HPV and its possible consequence of cervical carcinoma.

Increasing vaccine potency through exosome antigen targeting.

Science.gov (United States)

Hartman, Zachary C; Wei, Junping; Glass, Oliver K; Guo, Hongtao; Lei, Gangjun; Yang, Xiao-Yi; Osada, Takuya; Hobeika, Amy; Delcayre, Alain; Le Pecq, Jean-Bernard; Morse, Michael A; Clay, Timothy M; Lyerly, Herbert K

2011-11-21

While many tumor associated antigens (TAAs) have been identified in human cancers, efforts to develop efficient TAA "cancer vaccines" using classical vaccine approaches have been largely ineffective. Recently, a process to specifically target proteins to exosomes has been established which takes advantage of the ability of the factor V like C1C2 domain of lactadherin to specifically address proteins to exosomes. Using this approach, we hypothesized that TAAs could be targeted to exosomes to potentially increase their immunogenicity, as exosomes have been demonstrated to traffic to antigen presenting cells (APC). To investigate this possibility, we created adenoviral vectors expressing the extracellular domain (ECD) of two non-mutated TAAs often found in tumors of cancer patients, carcinoembryonic antigen (CEA) and HER2, and coupled them to the C1C2 domain of lactadherin. We found that these C1C2 fusion proteins had enhanced expression in exosomes in vitro. We saw significant improvement in antigen specific immune responses to each of these antigens in naïve and tolerant transgenic animal models and could further demonstrate significantly enhanced therapeutic anti-tumor effects in a human HER2+ transgenic animal model. These findings demonstrate that the mode of secretion and trafficking can influence the immunogenicity of different human TAAs, and may explain the lack of immunogenicity of non-mutated TAAs found in cancer patients. They suggest that exosomal targeting could enhance future anti-tumor vaccination protocols. This targeting exosome process could also be adapted for the development of more potent vaccines in some viral and parasitic diseases where the classical vaccine approach has demonstrated limitations. Copyright © 2011 Elsevier Ltd. All rights reserved.

Therapeutic Vaccine Against Primate Papillomavirus Infections of the Cervix

DEFF Research Database (Denmark)

Ragonnaud, Emeline; Andersson, Anne-Marie C; Mariya, Silmi

2017-01-01

Currently available prophylactic vaccines have no therapeutic efficacy for preexisting human papillomavirus (HPVs) infections, do not target all oncogenic HPVs and are insufficient to eliminate the burden of HPV induced cancer. We aim to develop an alternative HPV vaccine which is broadly effective...

A History of the Development of Brucella Vaccines

OpenAIRE

Avila-Calder?n, Eric Daniel; Lopez-Merino, Ahid?; Sriranganathan, Nammalwar; Boyle, Stephen M.; Contreras-Rodr?guez, 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. CONACYT CB-2011-01, 169259 SIP-IPN 20110891, 20134610 ICYTDF-IPN (Project of Investiga...

Translational cancer vaccine: from mouse to human to cat

Science.gov (United States)

Levenson, Richard

2015-03-01

Acanthomatous ameloblastoma is a locally invasive tumor arising in the gingiva that can progress rapidly, invade and destroy bone. If the lesion involves the upper jaw, surgical excision may not be possible and while local control is imperative, other therapies have not been fully evaluated. The primary author's personal cat, Gabriella, developed this tumor, with gingival masses around teeth in the upper jaw and evidence of widespread bony destruction of the hard palate. Because of his involvement with Immunophotonics Inc. as an advisor, the author was aware of an in situ autologous cancer vaccine (inCVAX) that is currently under development by the company. One session was performed in a veterinary clinic in Arkansas, and two follow-up sessions at the small animal hospital at the UC Davis veterinary school. No other therapy was provided. As of this writing, 3+ years after first treatment and 3 years, 4 months after presentation, Gabriella is well, with no evidence of disease.

Oral vaccination with attenuated Salmonella choleraesuis C500 ...

African Journals Online (AJOL)

Helicobacter pylori are well known as the major gastro-duodenal pathogen of peptic ulcer disease and gastric cancer. Recombinant H. pylori vaccine comprising a single subunit antigen can only induce immune response with limited protection efficiency. Development of oral vaccine would be a new effective strategy for the ...

Freund's vaccine adjuvant promotes Her2/Neu breast cancer

International Nuclear Information System (INIS)

Cotroneo, Michelle S; Haag, Jill D; Stapel, Nicholas R; Waller, Jordy L; Woditschka, Stephan; Gould, Michael N

2009-01-01

Inflammation has been linked to the etiology of many organ-specific cancers. Indirect evidence suggests a possible role for inflammation in breast cancer. We investigated whether the systemic inflammation induced by Freund's adjuvant (FA) promotes mammary carcinogenesis in a rat model in which cancer is induced by the neu oncogene. The effects of FA on hyperplastic mammary lesions and mammary carcinomas were determined in a neu-induced rat model. The inflammatory response to FA treatment was gauged by measuring acute phase serum haptoglobin. In addition, changes in cell proliferation and apoptosis following FA treatment were assessed. Rats receiving FA developed twice the number of mammary carcinomas as controls. Systemic inflammation following FA treatment is chronic, as shown by a doubling of the levels of the serum biomarker, haptoglobin, 15 days following initial treatment. We also show that this systemic inflammation is associated with the increased growth of hyperplastic mammary lesions. This increased growth results from a higher rate of cellular proliferation in the absence of changes in apoptosis. Our data suggests that systemic inflammation induced by Freund's adjuvant (FA) promotes mammary carcinogenesis. It will be important to determine whether adjuvants currently used in human vaccines also promote breast cancer

Cancer vaccine enhanced, non-tumor-reactive CD8(+) T cells exhibit a distinct molecular program associated with "division arrest anergy".

Science.gov (United States)

Beyer, Marc; Karbach, Julia; Mallmann, Michael R; Zander, Thomas; Eggle, Daniela; Classen, Sabine; Debey-Pascher, Svenja; Famulok, Michael; Jäger, Elke; Schultze, Joachim L

2009-05-15

Immune-mediated tumor rejection relies on fully functional T-cell responses and neutralization of an adverse tumor microenvironment. In clinical trials, we detected peptide-specific but non-tumor-reactive and therefore not fully functional CD8(+) T cells post-vaccination against tumor antigens. Understanding the molecular mechanisms behind nontumor reactivity will be a prerequisite to overcome this CD8(+) T-cell deviation. We report that these non-tumor-reactive CD8(+) T cells are characterized by a molecular program associated with hallmarks of "division arrest anergy." Non-tumor-reactive CD8(+) T cells are characterized by coexpression of CD7, CD25, and CD69 as well as elevated levels of lck(p505) and p27(kip1). In vivo quantification revealed high prevalence of non-tumor-reactive CD8(+) T cells with increased levels during cancer vaccination. Furthermore, their presence was associated with a trend toward shorter survival. Dynamics and frequencies of non-target-reactive CD8(+) T cells need to be further addressed in context of therapeutic vaccine development in cancer, chronic infections, and autoimmune diseases.

Nanotechnology in the management of cervical cancer.

Science.gov (United States)

Chen, Jiezhong; Gu, Wenyi; Yang, Lei; Chen, Chen; Shao, Renfu; Xu, Kewei; Xu, Zhi Ping

2015-03-01

Cervical cancer is a major disease with high mortality. All cervical cancers are caused by infection with human papillomaviruses (HPV). Although preventive vaccines for cervical cancer are successful, treatment of cervical cancer is far less satisfactory because of multidrug resistance and side effects. In this review, we summarize the recent application of nanotechnology to the diagnosis and treatment of cervical cancer as well as the development of HPV vaccines. Early detection of cervical cancer enables tumours to be efficiently removed by surgical procedures, leading to increased survival rate. The current method of detecting cervical cancer by Pap smear can only achieve 50% sensitivity, whereas nanotechnology has been used to detect HPVs with greatly improved sensitivity. In cervical cancer treatment, nanotechnology has been used for the delivery of anticancer drugs to increase treatment efficacy and decrease side effects. Nanodelivery of HPV preventive and therapeutic vaccines has also been investigated to increase vaccine efficacy. Overall, these developments suggest that nanoparticle-based vaccine may become the most effective way to prevent and treat cervical cancer, assisted or combined with some other nanotechnology-based therapy. Copyright © 2015 John Wiley & Sons, Ltd.

Gene-based vaccine development for improving animal production in developing countries. Possibilities and constraints

International Nuclear Information System (INIS)

Egerton, J.R.

2005-01-01

For vaccine production, recombinant antigens must be protective. Identifying protective antigens or candidate antigens is an essential precursor to vaccine development. Even when a protective antigen has been identified, cloning of its gene does not lead directly to vaccine development. The fimbrial protein of Dichelobacter nodosus, the agent of foot-rot in ruminants, was known to be protective. Recombinant vaccines against this infection are ineffective if expressed protein subunits are not assembled as mature fimbriae. Antigenic competition between different, but closely related, recombinant antigens limited the use of multivalent vaccines based on this technology. Recombinant antigens may need adjuvants to enhance response. DNA vaccines, potentiated with genes for different cytokines, may replace the need for aggressive adjuvants, and especially where cellular immunity is essential for protection. The expression of antigens from animal pathogens in plants and the demonstration of some immunity to a disease like rinderpest after ingestion of these, suggests an alternative approach to vaccination by injection. Research on disease pathogenesis and the identification of candidate antigens is specific to the disease agent. The definition of expression systems and the formulation of a vaccine for each disease must be followed by research to establish safety and efficacy. Where vaccines are based on unique gene sequences, the intellectual property is likely to be protected by patent. Organizations, licensed to produce recombinant vaccines, expect to recover their costs and to make a profit. The consequence is that genetically-derived vaccines are expensive. The capacity of vaccines to help animal owners of poorer countries depends not only on quality and cost but also on the veterinary infrastructure where they are used. Ensuring the existence of an effective animal health infrastructure in developing countries is as great a challenge for the developed world as

Androgen Ablation Augments Prostate Cancer Vaccine Immunogenicity Only When Applied After Immunization

Science.gov (United States)

Koh, Yi T.; Gray, Andrew; Higgins, Sean A.; Hubby, Bolyn; Kast, W. Martin

2009-01-01

Background Androgen ablation (AA) causes apoptosis of normal and neoplastic prostate cells. It is a standard treatment for advanced prostate cancer. Androgen ablation-mediated immunological effects include bone marrow hyperplasia, thymic regeneration, T and B cell lymphopoeisis and restoration of age-related peripheral T cell dysfunction. Androgens also regulate the transcription of several cytokines. Dendritic cells (DC) are the most potent antigen presenting cells that can activate antigen-specific naïve T cells. Despite myriad clinical trials involving DC-based prostate cancer immunotherapies, the effects of AA on DC function remain largely uncharacterized. Therefore, we investigated the effects of AA on DC and whether it could improve the efficacy of prostate cancer immunotherapy. Methods Cytokine expression changes due to AA were quantified by multiplex ELISA. Flow cytometry was used to assess AA-mediated effects on DC maturation and expression of costimulatory markers. Mixed leukocyte reactions and cell-mediated lysis assays elucidated the role of androgens in DC function. The effect of AA on the efficacy of vaccination against a prostate tumor-associated antigen was tested using Elispot assays. Results Androgen ablation increased dendritic cell maturation and costimulatory marker expression, but had no effect on DC costimulatory function. However, DC isolated from castrated mice increased the expression of key cytokines by antigen-experienced T cells while decreasing their expression in naïve cells. Finally, androgen ablation improved immune responses to vaccination only when applied after immunization. Conclusion Androgen ablation causes differential effects of DC on primary and secondary T cell responses, thus augmenting vaccine immunogenicity only when applied after immunization. PMID:19143030

Low rate of human papillomavirus vaccination among schoolgirls in Lebanon: barriers to vaccination with a focus on mothers’ knowledge about available vaccines

Directory of Open Access Journals (Sweden)

Abou El-Ola MJ

2018-03-01

Full Text Available Maria J Abou El-Ola,1 Mariam A Rajab,2 Dania I Abdallah,3 Ismail A Fawaz,4 Lyn S Awad,5 Hani M Tamim,6 Ahmad O Ibrahim,7 Anas M Mugharbil,7 Rima A Moghnieh8 1Department of Obstetrics and Gynaecology, Makassed General Hospital, Beirut, Lebanon; 2Department of Pediatrics, Makassed General Hospital, Beirut, Lebanon; 3Department of Pharmacy, Makassed General Hospital, Beirut, Lebanon; 4Department of Internal Medicine, Iklim Health Foundation Hospital, Mazboud, Mount Lebanon, Chouf, Lebanon; 5Department of Pharmacy, Makassed General Hospital, Beirut, Lebanon; 6Department of Internal Medicine, American University of Beirut, Beirut, Lebanon; 7Division of Hematology/Oncology, Department of Internal Medicine, Makassed General Hospital, Beirut, Lebanon; 8Division of Infectious Diseases, Department of Internal Medicine, Makassed General Hospital, Beirut, Lebanon Background: Human papillomavirus (HPV infection is an established predisposing factor of cervical cancer. In this study, we assessed the awareness about genital warts, cervical cancer, and HPV vaccine among mothers having girls who are at the age of primary HPV vaccination attending a group of schools in Lebanon. We also assessed the rate of HPV vaccination among these girls and the barriers to vaccination in this community. Subjects and methods: This is a cross-sectional, school-based survey. A 23-item, self-administered, anonymous, pretested, structured questionnaire with closed-ended questions was used to obtain data. The questionnaire was sent to the mothers through their student girls, and they were asked to return it within a week. Data were analyzed using the Statistical Package for Social Sciences version 21.0. Bivariate analysis was performed using the chi-square test to compare categorical variables, whereas continuous variables were compared using the Student’s t-test. Fisher’s exact test was used when chi-square test could not be employed. Results: The response rate in our survey

Novel Platforms for the Development of a Universal Influenza Vaccine

Directory of Open Access Journals (Sweden)

Arun Kumar

2018-03-01

Full Text Available Despite advancements in immunotherapeutic approaches, influenza continues to cause severe illness, particularly among immunocompromised individuals, young children, and elderly adults. Vaccination is the most effective way to reduce rates of morbidity and mortality caused by influenza viruses. Frequent genetic shift and drift among influenza-virus strains with the resultant disparity between circulating and vaccine virus strains limits the effectiveness of the available conventional influenza vaccines. One approach to overcome this limitation is to develop a universal influenza vaccine that could provide protection against all subtypes of influenza viruses. Moreover, the development of a novel or improved universal influenza vaccines may be greatly facilitated by new technologies including virus-like particles, T-cell-inducing peptides and recombinant proteins, synthetic viruses, broadly neutralizing antibodies, and nucleic acid-based vaccines. This review discusses recent scientific advances in the development of next-generation universal influenza vaccines.

Predictors of Adults' Knowledge and Awareness of HPV, HPV-Associated Cancers, and the HPV Vaccine: Implications for Health Education

Science.gov (United States)

McBride, Kimberly R.; Singh, Shipra

2018-01-01

High human papillomavirus (HPV) prevalence and low HPV vaccine uptake are significant public health concerns. Disparities in HPV-associated cancers and HPV vaccine uptake rates suggest the need for additional research examining factors associated with vaccine acceptance. This study assessed HPV awareness and knowledge and identified…

Cervical cancer screening in partly HPV vaccinated cohorts - A cost-effectiveness analysis

NARCIS (Netherlands)

S.K. Naber (Steffie); S.M. Matthijsse (Suzette); K. Rozemeijer (Kirsten); C. Penning (Corine); I.M.C.M. de Kok (Inge); M. van Ballegooijen (Marjolein)

2016-01-01

textabstractBackground: Vaccination against the oncogenic human papillomavirus (HPV) types 16 and 18 will reduce the prevalence of these types, thereby also reducing cervical cancer risk in unvaccinated women. This (measurable) herd effect will be limited at first, but is expected to increase over

Simultaneous approach using systemic, mucosal and transcutaneous routes of immunization for development of protective HIV-1 vaccines.

Science.gov (United States)

Belyakov, I M; Ahlers, J D

2011-01-01

Mucosal tissues are major sites of HIV entry and initial infection. Induction of a local mucosal cytotoxic T lymphocyte response is considered an important goal in developing an effective HIV vaccine. In addition, activation and recruitment of memory CD4(+) and CD8(+) T cells in systemic lymphoid circulation to mucosal effector sites might provide the firewall needed to prevent virus spread. Therefore a vaccine that generates CD4(+) and CD8(+) responses in both mucosal and systemic tissues might be required for protection against HIV. However, optimal routes and number of vaccinations required for the generation of long lasting CD4(+) and CD8(+) CTL effector and memory responses are not well understood especially for mucosal T cells. A number of studies looking at protective immune responses against diverse mucosal pathogens have shown that mucosal vaccination is necessary to induce a compartmentalized immune response including maximum levels of mucosal high-avidity CD8(+) CTL, antigen specific mucosal antibodies titers (especially sIgA), as well as induction of innate anti-viral factors in mucosa tissue. Immune responses are detectable at mucosal sites after systemic delivery of vaccine, and prime boost regimens can amplify the magnitude of immune responses in mucosal sites and in systemic lymphoid tissues. We believe that the most optimal mucosal and systemic HIV/SIV specific protective immune responses and innate factors might best be achieved by simultaneous mucosal and systemic prime and boost vaccinations. Similar principals of vaccination may be applied for vaccine development against cancer and highly invasive pathogens that lead to chronic infection.

[Dengue, zika, chikungunya and the development of vaccines].

Science.gov (United States)

Kantor, Isabel N

2018-01-01

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.

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.

The HPV Vaccine - What the Family Practitioner Needs to Know ...

African Journals Online (AJOL)

This article reviews the impact of human papilloma virus infection on the development of cervical cancer and the efficacy of newly developed HPV vaccines. These vaccines may have a major impact on the reduction of these common malignancies. South African Journal of Family Practice Vol. 50 (4) 2008: pp. 22-24 ...

Epidemiological Studies to Support the Development of Next Generation Influenza Vaccines.

Science.gov (United States)

Petrie, Joshua G; Gordon, Aubree

2018-03-26

The National Institute of Allergy and Infectious Diseases recently published a strategic plan for the development of a universal influenza vaccine. This plan focuses on improving understanding of influenza infection, the development of influenza immunity, and rational design of new vaccines. Epidemiological studies such as prospective, longitudinal cohort studies are essential to the completion of these objectives. In this review, we discuss the contributions of epidemiological studies to our current knowledge of vaccines and correlates of immunity, and how they can contribute to the development and evaluation of the next generation of influenza vaccines. These studies have been critical in monitoring the effectiveness of current influenza vaccines, identifying issues such as low vaccine effectiveness, reduced effectiveness among those who receive repeated vaccination, and issues related to egg adaptation during the manufacturing process. Epidemiological studies have also identified population-level correlates of protection that can inform the design and development of next generation influenza vaccines. Going forward, there is an enduring need for epidemiological studies to continue advancing knowledge of correlates of protection and the development of immunity, to evaluate and monitor the effectiveness of next generation influenza vaccines, and to inform recommendations for their use.

A survey of awareness of Pap smear and cervical cancer vaccine among women at tertiary care centre in Eastern Uttar Pradesh India

OpenAIRE

Anjali Rani; Kalpana Singh; Shreya Thapa

2015-01-01

Background: Cervical cancer is very common in developing countries. In Uttar Pradesh the literacy rate of women is low as compared to other states of India. Poverty is very high. Most women report with advance stage of cervical cancer. It can be prevented by early screening with Pap smear. Aim of our study is to know about the awareness of Pap smear and cervical cancer vaccine among women attending a tertiary hospital in Eastern part of Uttar Pradesh India. Methods: A questionnaire based ...

Modeling protective anti-tumor immunity via preventative cancer vaccines using a hybrid agent-based and delay differential equation approach.

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Kim, Peter S; Lee, Peter P

2012-01-01

A next generation approach to cancer envisions developing preventative vaccinations to stimulate a person's immune cells, particularly cytotoxic T lymphocytes (CTLs), to eliminate incipient tumors before clinical detection. The purpose of our study is to quantitatively assess whether such an approach would be feasible, and if so, how many anti-cancer CTLs would have to be primed against tumor antigen to provide significant protection. To understand the relevant dynamics, we develop a two-compartment model of tumor-immune interactions at the tumor site and the draining lymph node. We model interactions at the tumor site using an agent-based model (ABM) and dynamics in the lymph node using a system of delay differential equations (DDEs). We combine the models into a hybrid ABM-DDE system and investigate dynamics over a wide range of parameters, including cell proliferation rates, tumor antigenicity, CTL recruitment times, and initial memory CTL populations. Our results indicate that an anti-cancer memory CTL pool of 3% or less can successfully eradicate a tumor population over a wide range of model parameters, implying that a vaccination approach is feasible. In addition, sensitivity analysis of our model reveals conditions that will result in rapid tumor destruction, oscillation, and polynomial rather than exponential decline in the tumor population due to tumor geometry.

Cancer Antigen Prioritization: A Road Map to Work in Defining Vaccines Against Specific Targets. A Point of View

International Nuclear Information System (INIS)

Gomez, Daniel E.; Vázquez, Ana María; Alonso, Daniel F.

2012-01-01

The use of anti-idiotype antibodies as vaccines to stimulate antitumor immunity is a very promising pathway in the therapy of cancer. A good body of work in animal tumor models have demonstrated the efficacy of anti-Id vaccines in preventing tumor growth and curing mice with established tumors. A number of monoclonal anti-Id antibodies that mimic different human tumor-associated antigens (TAAs) have been developed and tested in the clinic, demonstrating interesting. In general terms, the antigen mimicry by anti-Id antibodies has reflected structural homology in the most of the cases, and amino acid sequence homology in a minority of them. The major challenge of immunotherapy using anti-idiotype vaccines is to identify the optimal anti-idiotype antibody that will function as a true surrogate antigen for a TAA system, and ideally will generate both humoral and cellular immune responses. Several clinical studies have shown enhanced patient's survival when receiving anti-Id vaccines, the true demonstration of efficacy of these vaccines will depend upon the results of several randomized Phase III clinical trials that are currently planned or ongoing (Bhattacharya-Chatterjee et al.,).

Cancer Antigen Prioritization: A Road Map to Work in Defining Vaccines Against Specific Targets. A Point of View

Energy Technology Data Exchange (ETDEWEB)

Gomez, Daniel E. [Laboratory of Molecular Oncology, Quilmes National University, Buenos Aires (Argentina); Vázquez, Ana María [Center of Molecular Immunology, La Habana (Cuba); Alonso, Daniel F., E-mail: degomez@unq.edu.ar [Laboratory of Molecular Oncology, Quilmes National University, Buenos Aires (Argentina)

2012-06-28

The use of anti-idiotype antibodies as vaccines to stimulate antitumor immunity is a very promising pathway in the therapy of cancer. A good body of work in animal tumor models have demonstrated the efficacy of anti-Id vaccines in preventing tumor growth and curing mice with established tumors. A number of monoclonal anti-Id antibodies that mimic different human tumor-associated antigens (TAAs) have been developed and tested in the clinic, demonstrating interesting. In general terms, the antigen mimicry by anti-Id antibodies has reflected structural homology in the most of the cases, and amino acid sequence homology in a minority of them. The major challenge of immunotherapy using anti-idiotype vaccines is to identify the optimal anti-idiotype antibody that will function as a true surrogate antigen for a TAA system, and ideally will generate both humoral and cellular immune responses. Several clinical studies have shown enhanced patient's survival when receiving anti-Id vaccines, the true demonstration of efficacy of these vaccines will depend upon the results of several randomized Phase III clinical trials that are currently planned or ongoing (Bhattacharya-Chatterjee et al.,).

Immunotherapeutic strategies for cancer treatment: a novel protein transfer approach for cancer vaccine development.

Science.gov (United States)

Shashidharamurthy, Rangaiah; Bozeman, Erica N; Patel, Jaina; Kaur, Ramneet; Meganathan, Jeyandra; Selvaraj, Periasamy

2012-11-01

Cancer cells have developed numerous ways to escape immune surveillance and gain unlimited proliferative capacity. Currently, several chemotherapeutic agents and radiotherapy, either alone or in combination, are being used to treat malignancies. However, both of these therapies are associated with several limitations and detrimental side effects. Therefore, recent scientific investigations suggest that immunotherapy is among the most promising new approaches in modern cancer therapy. The focus of cancer immunotherapy is to boost both acquired and innate immunity against malignancies by specifically targeting tumor cells, and leaving healthy cells and tissues unharmed. Cellular, cytokine, gene, and monoclonal antibody therapies have progressively become promising immunotherapeutic approaches that are being tested for several cancers in preclinical models as well as in the clinic. In this review, we discuss recent advances in these immunotherapeutic approaches, focusing on new strategies that allow the expression of specific immunostimulatory molecules on the surface of tumor cells to induce robust antitumor immunity. © 2011 Wiley Periodicals, Inc.

Vaxvec: The first web-based recombinant vaccine vector database and its data analysis

Science.gov (United States)

Deng, Shunzhou; Martin, Carly; Patil, Rasika; Zhu, Felix; Zhao, Bin; Xiang, Zuoshuang; He, Yongqun

2015-01-01

A recombinant vector vaccine uses an attenuated virus, bacterium, or parasite as the carrier to express a heterologous antigen(s). Many recombinant vaccine vectors and related vaccines have been developed and extensively investigated. To compare and better understand recombinant vectors and vaccines, we have generated Vaxvec (http://www.violinet.org/vaxvec), the first web-based database that stores various recombinant vaccine vectors and those experimentally verified vaccines that use these vectors. Vaxvec has now included 59 vaccine vectors that have been used in 196 recombinant vector vaccines against 66 pathogens and cancers. These vectors are classified to 41 viral vectors, 15 bacterial vectors, 1 parasitic vector, and 1 fungal vector. The most commonly used viral vaccine vectors are double-stranded DNA viruses, including herpesviruses, adenoviruses, and poxviruses. For example, Vaxvec includes 63 poxvirus-based recombinant vaccines for over 20 pathogens and cancers. Vaxvec collects 30 recombinant vector influenza vaccines that use 17 recombinant vectors and were experimentally tested in 7 animal models. In addition, over 60 protective antigens used in recombinant vector vaccines are annotated and analyzed. User-friendly web-interfaces are available for querying various data in Vaxvec. To support data exchange, the information of vaccine vectors, vaccines, and related information is stored in the Vaccine Ontology (VO). Vaxvec is a timely and vital source of vaccine vector database and facilitates efficient vaccine vector research and development. PMID:26403370

"Communicate to vaccinate": the development of a taxonomy of communication interventions to improve routine childhood vaccination.

Science.gov (United States)

Willis, Natalie; Hill, Sophie; Kaufman, Jessica; Lewin, Simon; Kis-Rigo, John; De Castro Freire, Sara Bensaude; Bosch-Capblanch, Xavier; Glenton, Claire; Lin, Vivian; Robinson, Priscilla; Wiysonge, Charles S

2013-05-11

Vaccination is a cost-effective public health measure and is central to the Millennium Development Goal of reducing child mortality. However, childhood vaccination coverage remains sub-optimal in many settings. While communication is a key feature of vaccination programmes, we are not aware of any comprehensive approach to organising the broad range of communication interventions that can be delivered to parents and communities to improve vaccination coverage. Developing a classification system (taxonomy) organised into conceptually similar categories will aid in: understanding the relationships between different types of communication interventions; facilitating conceptual mapping of these interventions; clarifying the key purposes and features of interventions to aid implementation and evaluation; and identifying areas where evidence is strong and where there are gaps. This paper reports on the development of the 'Communicate to vaccinate' taxonomy. The taxonomy was developed in two stages. Stage 1 included: 1) forming an advisory group; 2) searching for descriptions of interventions in trials (CENTRAL database) and general health literature (Medline); 3) developing a sampling strategy; 4) screening the search results; 5) developing a data extraction form; and 6) extracting intervention data. Stage 2 included: 1) grouping the interventions according to purpose; 2) holding deliberative forums in English and French with key vaccination stakeholders to gather feedback; 3) conducting a targeted search of grey literature to supplement the taxonomy; 4) finalising the taxonomy based on the input provided. The taxonomy includes seven main categories of communication interventions: inform or educate, remind or recall, teach skills, provide support, facilitate decision making, enable communication and enhance community ownership. These categories are broken down into 43 intervention types across three target groups: parents or soon-to-be-parents; communities, community

Next-Generation Dengue Vaccines: Novel Strategies Currently Under Development

OpenAIRE

Anna P. Durbin; Stephen S. Whitehead

2011-01-01

Dengue has become the most important arboviral infection worldwide with more than 30 million cases of dengue fever estimated to occur each year. The need for a dengue vaccine is great and several live attenuated dengue candidate vaccines are proceeding through clinical evaluation. The need to induce a balanced immune response against all four DENV serotypes with a single vaccine has been a challenge for dengue vaccine developers. A live attenuated DENV chimeric vaccine produced by Sanofi Past...

Estimating the cost-effectiveness profile of a universal vaccination programme with a nine-valent HPV vaccine in Austria.

Science.gov (United States)

Boiron, L; Joura, E; Largeron, N; Prager, B; Uhart, M

2016-04-16

HPV is a major cancer-causing factor in both sexes in the cervix, vulva, vagina, anus, penis, oropharynx as well as the causal factor in other diseases such as genital warts and recurrent respiratory papillomatis. In the context of the arrival of a nonavalent HPV vaccine (6/11/16/18/31/33/45/52/58), this analysis aims to estimate the public health impact and the incremental cost-effectiveness of a universal (girls and boys) vaccination program with a nonavalent HPV vaccine as compared to the current universal vaccination program with a quadrivalent HPV vaccine (6/11/16/18), in Austria. A dynamic transmission model including a wide range of health and cost outcomes related to cervical, anal, vulvar, vaginal diseases and genital warts was calibrated to Austrian epidemiological data. The clinical impact due to the 5 new types was included for cervical and anal diseases outcomes only. In the base case, a two-dose schedule, lifelong vaccine type-specific protection and a vaccination coverage rate of 60% and 40% for girls and boys respectively for the 9-year old cohorts were assumed. A cost-effectiveness threshold of €30,000/QALY-gained was considered. Universal vaccination with the nonavalent vaccine was shown to reduce the incidence of HPV16/18/31/33/45/52/58 -related cervical cancer by 92%, the related CIN2/3 cases by 96% and anal cancer by 83% and 76% respectively in females and males after 100 years, relative to 75%, 76%, 80% and 74% with the quadrivalent vaccine, respectively. Furthermore, the nonavalent vaccine was projected to prevent an additional 14,893 cases of CIN2/3 and 2544 cases of cervical cancer, over 100 years. Depending on the vaccine price, the strategy was shown to be from cost-saving to cost-effective. The present evaluation showed that vaccinating 60% of girls and 40% of boys aged 9 in Austria with a 9-valent vaccine will substantially reduce the incidence of cervical cancer, CIN and anal cancer compared to the existing strategy. The vaccination

Checkpoint blockade in combination with cancer vaccines.

Science.gov (United States)

Morse, Michael A; Lyerly, H Kim

2015-12-16

Checkpoint blockade, prevention of inhibitory signaling that limits activation or function of tumor antigen-specific T cells responses, is revolutionizing the treatment of many poor prognosis malignancies. Indeed monoclonal antibodies that modulate signaling through the inhibitory molecules CTLA-4 and PD-1 are now clinically available; however, many tumors, demonstrate minimal response suggesting the need for combinations with other therapeutic strategies. Because an inadequate frequency of activated tumor antigen-specific T cells in the tumor environment, the so-called non-inflamed phenotype, is observed in some malignancies, other rationale partners are modalities that lead to enhanced T cell activation (vaccines, cytokines, toll-like receptor agonists, and other anticancer therapies such as chemo-, radio- or targeted therapies that lead to release of antigen from tumors). This review will focus on preclinical and clinical data supporting the use of cancer vaccines with anti-CTLA-4 and anti-PD-1/PD-L1 antibodies. Preliminary preclinical data demonstrate enhanced antitumor activity although the results in human studies are less clear. Broader combinations of multiple immune modulators are now under study. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effect of 25-Hydroxyvitamin D Status on Serological Response to Influenza Vaccine in Prostate Cancer Patients

Science.gov (United States)

Chadha, Manpreet K.; Fakih, Marwan; Muindi, Josephia; Tian, Lili; Mashtare, Terry; Johnson, Candace S.; Trump, Donald

2015-01-01

BACKGROUND Epidemiologic data suggest that there is an association between vitamin D deficiency and influenza infection. We conducted a prospective influenza vaccination study to determine the influence of vitamin D status on serological response to influenza vaccine in prostate cancer (CaP) patients. METHODS During the 2006–2007 influenza season, CaP patients treated at Roswell Park Cancer Institute were offered vaccination with the trivalent influenza vaccine (Fluzone®, 2006–2007) and sera collected for hemagglutination inhibition (HI) assay titers before and 3 months after vaccination. Response to vaccination was defined as ≥1:40 titer ratio or a fourfold increase in titer at 3 months, against any of the three strains. Serum 25-hydroxyvitamin D (25-D3) levels were measured using DiaSorin 125I radioimmunoassay kits. RESULTS Thirty-five patients with CaP participated in the study. Median baseline 25-D3 level was 44.88 ng/ml (range: 9.16–71.98 ng/ml) Serological response against any of the three strains was noted in 80%. There was a significant effect of baseline 25-D3 level when tested as a continuous variable in relation to serological response (P = 0.0446). All patients in the upper quartile of 25-D3 level responded by mounting a serological response (P = 0.0344). None of the other baseline variables (age, race, chemotherapy status, or white cell count) had an effect on serological response. CONCLUSIONS In this study in CaP patients, a replete vitamin D status was associated with more frequent serological response to influenza vaccine. PMID:20812224

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.

Knowledge and Awareness of HPV Vaccine and Acceptability to Vaccinate in Sub-Saharan Africa: A Systematic Review

Science.gov (United States)

Perlman, Stacey; Wamai, Richard G.; Bain, Paul A.; Welty, Thomas; Welty, Edith; Ogembo, Javier Gordon

2014-01-01

Objectives We assessed the knowledge and awareness of cervical cancer, HPV and HPV vaccine, and willingness and acceptability to vaccinate in sub-Saharan African (SSA) countries. We further identified countries that fulfill the two GAVI Alliance eligibility criteria to support nationwide HPV vaccination. Methods We conducted a systematic review of peer-reviewed studies on the knowledge and awareness of cervical cancer, HPV and HPV vaccine, and willingness and acceptability to vaccinate. Trends in Diphtheria-tetanus-pertussis (DTP3) vaccine coverage in SSA countries from 1990–2011 were extracted from the World Health Organization database. Findings The review revealed high levels of willingness and acceptability of HPV vaccine but low levels of knowledge and awareness of cervical cancer, HPV or HPV vaccine. We identified only six countries to have met the two GAVI Alliance requirements for supporting introduction of HPV vaccine: 1) the ability to deliver multi-dose vaccines for no less than 50% of the target vaccination cohort in an average size district, and 2) achieving over 70% coverage of DTP3 vaccine nationally. From 2008 through 2011 all SSA countries, with the exception of Mauritania and Nigeria, have reached or maintained DTP3 coverage at 70% or above. Conclusion There is an urgent need for more education to inform the public about HPV, HPV vaccine, and cervical cancer, particularly to key demographics, (adolescents, parents and healthcare professionals), to leverage high levels of willingness and acceptability of HPV vaccine towards successful implementation of HPV vaccination programs. There is unpreparedness in most SSA countries to roll out national HPV vaccination as per the GAVI Alliance eligibility criteria for supporting introduction of the vaccine. In countries that have met 70% DTP3 coverage, pilot programs need to be rolled out to identify the best practice and strategies for delivering HPV vaccines to adolescents and also to qualify for GAVI

Strategies & recent development of transmission-blocking vaccines against Plasmodium falciparum

Directory of Open Access Journals (Sweden)

Neha Chaturvedi

2016-01-01

Full Text Available Transmission blocking malaria vaccines are aimed to block the development and maturity of sexual stages of parasite within mosquitoes. The vaccine candidate antigens (Pfs25, Pfs48/45, Pfs230 that have shown transmission blocking immunity in model systems are in different stages of development. These antigens are immunogenic with limited genetic diversity. Pfs25 is a leading candidate and currently in phase I clinical trial. Efforts are now focused on the cost-effective production of potent antigens using safe adjuvants and optimization of vaccine delivery system that are capable of inducing strong immune responses. This review addresses the potential usefulness, development strategies, challenges, clinical trials and current status of Plasmodium falciparum sexual stage malaria vaccine candidate antigens for the development of transmission-blocking vaccines.

A multilateral effort to develop DNA vaccines against falciparum malaria.

Science.gov (United States)

Kumar, Sanjai; Epstein, Judith E; Richie, Thomas L; Nkrumah, Francis K; Soisson, Lorraine; Carucci, Daniel J; Hoffman, Stephen L

2002-03-01

Scientists from several organizations worldwide are working together to develop a multistage, multigene DNA-based vaccine against Plasmodium falciparum malaria. This collaborative vaccine development effort is named Multi-Stage DNA-based Malaria Vaccine Operation. An advisory board of international experts in vaccinology, malariology and field trials provides the scientific oversight to support the operation. This article discusses the rationale for the approach, underlying concepts and the pre-clinical development process, and provides a brief outline of the plans for the clinical testing of a multistage, multiantigen malaria vaccine based on DNA plasmid immunization technology.

Vaccine process technology.

Science.gov (United States)

Josefsberg, Jessica O; Buckland, Barry

2012-06-01

The evolution of vaccines (e.g., live attenuated, recombinant) and vaccine production methods (e.g., in ovo, cell culture) are intimately tied to each other. As vaccine technology has advanced, the methods to produce the vaccine have advanced and new vaccine opportunities have been created. These technologies will continue to evolve as we strive for safer and more immunogenic vaccines and as our understanding of biology improves. The evolution of vaccine process technology has occurred in parallel to the remarkable growth in the development of therapeutic proteins as products; therefore, recent vaccine innovations can leverage the progress made in the broader biotechnology industry. Numerous important legacy vaccines are still in use today despite their traditional manufacturing processes, with further development focusing on improving stability (e.g., novel excipients) and updating formulation (e.g., combination vaccines) and delivery methods (e.g., skin patches). Modern vaccine development is currently exploiting a wide array of novel technologies to create safer and more efficacious vaccines including: viral vectors produced in animal cells, virus-like particles produced in yeast or insect cells, polysaccharide conjugation to carrier proteins, DNA plasmids produced in E. coli, and therapeutic cancer vaccines created by in vitro activation of patient leukocytes. Purification advances (e.g., membrane adsorption, precipitation) are increasing efficiency, while innovative analytical methods (e.g., microsphere-based multiplex assays, RNA microarrays) are improving process understanding. Novel adjuvants such as monophosphoryl lipid A, which acts on antigen presenting cell toll-like receptors, are expanding the previously conservative list of widely accepted vaccine adjuvants. As in other areas of biotechnology, process characterization by sophisticated analysis is critical not only to improve yields, but also to determine the final product quality. From a regulatory

A cost-utility analysis of adding a bivalent or quadrivalent HPV vaccine to the Irish cervical screening programme.

LENUS (Irish Health Repository)

Dee, Anne

2010-04-01

Cervical cancer is a leading cause of death worldwide, and in Ireland it is the ninth most commonly diagnosed cancer in women. Almost 100% of these cancers are caused by human papillomavirus (HPV) infection. Two newly developed vaccines against HPV infection have become available. This study is a cost-utility analysis of the HPV vaccine in Ireland, and it compares the cost-effectiveness profiles of the two vaccines.

Development of respiratory syncytial virus (RSV) vaccines for infants.

Science.gov (United States)

Gerretsen, Hannah E; Sande, Charles J

2017-06-01

2017 will mark the 60 th anniversary since the first isolation of RSV in children. In spite of concerted efforts over all these years, the goal of developing an effective vaccine against paediatric RSV disease has remained elusive. One of the main hurdles standing in the way of an effective vaccine is the fact that the age incidence of severe disease peaks within the first 3 months of life, providing limited opportunity for intervention. In addition to this complexity, the spectre of failed historical vaccines, which increased the risk of illness and death upon subsequent natural infection, has substantially increased the safety criteria against which modern vaccines will be assessed. This review traces the history of RSV vaccine development for young infants and analyses the potential reasons for the failure of historic vaccines. It also discusses recent breakthroughs in vaccine antigen design and the progressive evolution of platforms for the delivery of these antigens to seronegative infants. © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.