WorldWideScience

Sample records for cancer vaccine development

  1. Progress and controversies in developing cancer vaccines

    Directory of Open Access Journals (Sweden)

    Speiser Daniel E

    2005-04-01

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

  2. Therapeutic Prostate Cancer Vaccines: A Review of the Latest Developments

    OpenAIRE

    Mohebtash, Mahsa; Madan, Ravi A.; Gulley, James L.; Arlen, Philip M.

    2008-01-01

    Therapeutic cancer vaccines are well-tolerated immunotherapy modalities designed to activate the immune system to kill cancer cells without a significant effect on normal cells. Better understanding of tumor immunology has led to improved strategies in vaccine development, which have resulted in improved outcomes. This review discusses different types of cancer vaccines, focusing predominantly on prostate cancer vaccines because of the high prevalence of prostate cancer and the wide variety o...

  3. Challenges facing the development of cancer vaccines.

    Science.gov (United States)

    Fishman, Mayer

    2014-01-01

    Just like any other effective immunization in medicine, cancer vaccines need to have antigens with particular specificity and immunostimulatory features, the immune responses to be elicited in the body, and therapeutic effect-regression or prevention of the cancer-must be meaningful and clinically observable. There are many choices for cancer antigens, such as tissue-specific proteins, cancer-specific proteins, class I- or class II-restricted peptides derived from those, or in situ and whole-cell-derived products are some examples. Another translational issue is that cancer patients are heterogeneous with respect to the extent to which the immune system is already activated with potential to impact the tumor growth or, conversely, the extent to which the immune system has been impaired through a prior and ongoing interaction with the tumor. Conventional or immunologic tests have potential to define a subset of patients with better chance or response, so that particular vaccines can be tested. Treatment of cancer patients is expensive, and trials are slow. To meet these challenges in practical terms will require not only careful scientific technical work for product development, coordination with clinicians to define patient subsets with diseases that can show responses, but also a comprehensive, practical implementation so that we can unlock the full potential of anticancer vaccines.

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

    Science.gov (United States)

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

    2016-04-01

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

  5. Recent advances in the development of breast cancer vaccines

    Directory of Open Access Journals (Sweden)

    Milani A

    2014-10-01

    Full Text Available Andrea Milani,1 Dario Sangiolo,1 Massimo Aglietta,1,2 Giorgio Valabrega1,2 1Department of Oncology, University of Torino, Torino, Italy; 2FPO, Candiolo Cancer Institute, IRCCS, Torino, Italy Abstract: The manipulation of the immune system through the administration of a vaccine to direct an effective and long-lasting immune response against breast cancer (BC cells is an attractive strategy. Vaccines would have several theoretical advantages over standard therapies, including low toxicities, high specificity, and long-lasting efficacy due to the establishment of immunological memory. However, BC vaccines have failed to demonstrate meaningful results in clinical trials so far. This reflects the intrinsic difficulty in breaking the complex immune-escaping mechanisms developed by cancer cells. New vaccines should be able to elicit complex immunologic response involving multiple immune effectors such as cytotoxic and antibody-secreting B cells, innate immunity effectors, and memory cells. Moreover, especially in patients with large tumor burdens and metastatic disease, combining vaccines with other strategies, such as systemic BC therapies, passive immunotherapy, or immunomodulatory agents, could increase the effectiveness of each approach. Here, we review recent advances in BC vaccines, focusing on suitable targets and innovative strategies. We report results of most recent trials investigating active immunotherapy in BC and provide possible future perspectives in this field of research. Keywords: breast cancer, cancer vaccines, cancer immunology, HER2, MUC-1, hTERT

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

    Science.gov (United States)

    Mackiewicz, Jacek; Mackiewicz, Andrzej

    2009-12-25

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

  7. Evolution of animal models in cancer vaccine development.

    Science.gov (United States)

    Wei, Wei-Zen; Jones, Richard F; Juhasz, Csaba; Gibson, Heather; Veenstra, Jesse

    2015-12-16

    Advances in cancer vaccine development are facilitated by animal models reflecting key features of human cancer and its interface with host immunity. Several series of transplantable preneoplastic and neoplastic mouse mammary lesions have been used to delineate mechanisms of anti-tumor immunity. Mimicking immune tolerance to tumor-associated antigens (TAA) such as HER2/neu, transgenic mice developing spontaneous mammary tumors are strong model systems for pre-clinical vaccine testing. In these models, HER2 DNA vaccines are easily administered, well-tolerated, and induce both humoral and cellular immunity. Although engineered mouse strains have advanced cancer immunotherapy, basic shortcomings remain. For example, multiple mouse strains have to be tested to recapitulate genetic regulation of immune tolerance in humans. Outbred domestic felines more closely parallel humans in the natural development of HER2 positive breast cancer and their varying genetic background. Electrovaccination with heterologous HER2 DNA induces robust adaptive immune responses in cats. Importantly, homologous feline HER2 DNA with a single amino acid substitution elicits unique antibodies to feline mammary tumor cells, unlocking a new vaccine principle. As an alternative approach to targeted vaccination, non-surgical tumor ablation such as cryoablation induces anti-tumor immunity via in situ immunization, particularly when combined with toll-like receptor (TLR) agonist. As strategies for vaccination advance, non-invasive monitoring of host response becomes imperative. As an example, magnetic resonance imaging (MRI) and positron emission tomography (PET) scanning following administration of tryptophan metabolism tracer [11C]-alpha-methyl-tryptophan (AMT) provides non-invasive imaging of both tumor growth and metabolic activities. Because AMT is a substrate of indoleamine-pyrrole 2,3-dioxygenase (IDO), an enzyme that produces the immune regulatory molecule kynurenine, AMT imaging can provide

  8. Business models and opportunities for cancer vaccine developers.

    Science.gov (United States)

    Kudrin, Alex

    2012-10-01

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

  9. Development of a Vaccine Targeting Triple-Negative Breast Cancer

    Science.gov (United States)

    2012-09-01

    patients with breast cancer ; (2) To evaluate the immunogenicity, clinical efficacy, and safety of an IGF-IR class II polyepitope vaccine in a mouse... breast cancer cells. Molecular cancer therapeutics 1, 707-717 (2002). 15. Koebel, C.M., et al. Adaptive immunity maintains occult cancer in an...trastuzumab and HER2/neu-specific vaccination in patients with metastatic breast cancer . Journal of clinical oncology : official journal of the American

  10. Progress in the development of photodynamic-therapy-generated cancer vaccines

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    Korbelik, Mladen; Sun, Jinghai

    2003-07-01

    Upon giving an outline on vaccines in general, their history and priorities for future development, this paper gives a brief summary of the advances in the generation of cancer vaccines from the first attempts made over 100 years ago to those currently evaluted in clinical trials. This is followed by discussing hte intitial achievements in the investigation of cancer vaccines generated by photodynamic therapy (PDT). Recent contributions from our research to the understanding of how PDT-generated cancer vaccines work and their advantages compared to other types of cancer vaccines are discussed.

  11. Update on vaccine development for renal cell cancer

    Directory of Open Access Journals (Sweden)

    Nina Chi

    2010-08-01

    Full Text Available Nina Chi1, Jodi K Maranchie2,3, Leonard J Appleman3,4, Walter J Storkus1,3,51Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States; 2Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States; 3University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, United States; 4Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States; 5Department of Dermatology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USAAbstract: Renal cell carcinoma (RCC remains a significant health concern that frequently presents as metastatic disease at the time of initial diagnosis. Current first-line therapeutics for the advanced-stage RCC include antiangiogenic drugs that have yielded high rates of objective clinical response; however, these tend to be transient in nature, with many patients becoming refractory to chronic treatment with these agents. Adjuvant immunotherapies remain viable candidates to sustain disease-free and overall patient survival. In particular, vaccines designed to optimize the activation, maintenance, and recruitment of specific immunity within or into the tumor site continue to evolve. Based on the integration of increasingly refined immunomonitoring systems in both translational models and clinical trials, allowing for the improved understanding of treatment mechanism(s of action, further refined (combinational vaccine protocols are currently being developed and evaluated. This review provides a brief history of RCC vaccine development, discusses the successes and limitations in such approaches, and provides a rationale for developing combinational vaccine approaches that may provide improved clinical benefits to patients with RCC.Keywords: renal cell carcinoma, vaccines, immunotherapy, combinational therapy, cellular immunity

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    . Previous development of therapeutic cancer vaccines has largely been based on studies in mice, and the majority of these candidate vaccines failed to induce therapeutic responses in the subsequent human clinical trials. Given that antigen dose and vaccine volume in pigs are translatable to humans...... and the porcine immunome is closer related to the human counterpart, we here introduce pigs as a supplementary large animal model for human cancer vaccine development. IDO and RhoC, both important in human cancer development and progression, were used as vaccine targets and 12 pigs were immunized with overlapping......C-derived peptides across all groups with no adjuvant being superior. These findings support the further use of pigs as a large animal model for vaccine development against human cancer....

  13. Cancer Vaccines: A Brief Overview.

    Science.gov (United States)

    Thomas, Sunil; Prendergast, George C

    2016-01-01

    Vaccine approaches for cancer differ from traditional vaccine approaches for infectious disease in tending to focus on clearing active disease rather than preventing disease. In this review, we provide a brief overview of different types of vaccines and adjuvants that have been investigated for the purpose of controlling cancer burdens in patients, some of which are approved for clinical use or in late-stage clinical trials, such as the personalized dendritic cell vaccine sipuleucel-T (Provenge) and the recombinant viral prostate cancer vaccine PSA-TRICOM (Prostvac-VF). Vaccines against human viruses implicated in the development and progression of certain cancers, such as human papillomavirus in cervical cancer, are not considered here. Cancers express "altered self" antigens that tend to induce weaker responses than the "foreign" antigens expressed by infectious agents. Thus, immune stimulants and adjuvant approaches have been explored widely. Vaccine types considered include autologous patient-derived immune cell vaccines, tumor antigen-expressing recombinant virus vaccines, peptide vaccines, DNA vaccines, and heterologous whole-cell vaccines derived from established human tumor cell lines. Opportunities to develop effective cancer vaccines may benefit from seminal recent advances in understanding how immunosuppressive barricades are erected by tumors to mediate immune escape. In particular, targeted ablation of these barricades with novel agents, such as the immune checkpoint drug ipilimumab (anti-CTLA-4) approved recently for clinical use, may offer significant leverage to vaccinologists seeking to control and prevent malignancy.

  14. The pharmaceuticalization of sexual risk: vaccine development and the new politics of cancer prevention.

    Science.gov (United States)

    Mamo, Laura; Epstein, Steven

    2014-01-01

    Vaccine development is a core component of pharmaceutical industry activity and a key site for studying pharmaceuticalization processes. In recent decades, two so-called cancer vaccines have entered the U.S. medical marketplace: a vaccine targeting hepatitis B virus (HBV) to prevent liver cancers and a vaccine targeting human papillomavirus (HPV) to prevent cervical and other cancers. These viruses are two of six sexually transmissible infectious agents (STIs) that are causally linked to the development of cancers; collectively they reference an expanding approach to apprehending cancer that focuses attention simultaneously "inward" toward biomolecular processes and "outward" toward risk behaviors, sexual practices, and lifestyles. This paper juxtaposes the cases of HBV and HPV and their vaccine trajectories to analyze how vaccines, like pharmaceuticals more generally, are emblematic of contemporary pharmaceuticalization processes. We argue that individualized risk, in this case sexual risk, is produced and treated by scientific claims of links between STIs and cancers and through pharmaceutical company and biomedical practices. Simultaneous processes of sexualization and pharmaceuticalization mark these cases. Our comparison demonstrates that these processes are not uniform, and that the production of risks, subjects, and bodies depends not only on the specificities of vaccine development but also on the broader political and cultural frames within which sexuality is understood.

  15. 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.

  16. The pig as a large preclinical model for therapeutic human anti-cancer vaccine development

    DEFF Research Database (Denmark)

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

    2016-01-01

    Development of therapeutic cancer vaccines has largely been based on rodent models and the majority failed to establish therapeutic responses in clinical trials. We therefore used pigs as a large animal model for human cancer vaccine development due to the large similarity between the porcine...... and human immunome. We administered peptides derived from porcine IDO, a cancer antigen important in human disease, formulated in Th1-inducing adjuvants to outbred pigs. By in silico prediction 136 candidate IDO-derived peptides were identified and peptide-SLA class I complex stability measurements revealed...

  17. Perspectives on the development of a therapeutic HER-2 cancer vaccine.

    Science.gov (United States)

    Renard, Valéry; Leach, Dana R

    2007-09-27

    With good reason, the majority of cancer vaccines tested, or being tested, have targeted the induction of anti-tumour CTL responses. However, the clinical success of monoclonal antibodies such as Rituximab/CD20, Trastuzumab/HER-2, Cetuximab/EGFR and Bevacisumab/VEGF suggests that their respective targets may also be relevant for cancer vaccines aiming at the induction of an effective humoral anti-tumour response to mimic, or potentially improve upon, the effects of monoclonal therapies. We report here an overview of the development of a protein vaccine targeting HER-2/neu, with an emphasis on the immunologic results obtained from the testing of the vaccine in animal models of disease and in toxicology programs, to its evaluation in three clinical trials in breast cancer patients.

  18. Dissecting Cancer Vaccines

    Institute of Scientific and Technical Information of China (English)

    Jennifer Couzin; 丁东

    2004-01-01

    @@ If there's one thing cancer vaccine developers would like to know, it's why only a handful of patients respond strongly to their inventions. Now at an immunology② meeting here, a team of scientists reported that a set of patients with metastatic melanoma③ may be revealing an answer to that mysterious question.

  19. Vaccine Treatment for Prostate Cancer

    Science.gov (United States)

    ... Back After Treatment Prostate Cancer Treating Prostate Cancer Vaccine Treatment for Prostate Cancer Sipuleucel-T (Provenge) is ... less advanced prostate cancer. Possible side effects of vaccine treatment Side effects from the vaccine tend to ...

  20. Chemokines as Cancer Vaccine Adjuvants

    Directory of Open Access Journals (Sweden)

    Agne Petrosiute

    2013-10-01

    Full Text Available We are witnessing a new era of immune-mediated cancer therapies and vaccine development. As the field of cancer vaccines advances into clinical trials, overcoming low immunogenicity is a limiting step in achieving full success of this therapeutic approach. Recent discoveries in the many biological roles of chemokines in tumor immunology allow their exploitation in enhancing recruitment of antigen presenting cells (APCs and effector cells to appropriate anatomical sites. This knowledge, combined with advances in gene therapy and virology, allows researchers to employ chemokines as potential vaccine adjuvants. This review will focus on recent murine and human studies that use chemokines as therapeutic anti-cancer vaccine adjuvants.

  1. Strategies for Developing Oral Vaccines for Human Papillomavirus (HPV) Induced Cancer using Nanoparticle mediated Delivery System.

    Science.gov (United States)

    Uddin, Mohammad Nasir; Kouzi, Samir A; Hussain, Muhammad Delwar

    2015-01-01

    Human Papillomaviruses (HPV) are a diverse group of small non-enveloped DNA viruses. Some HPVs are classified as low-risk as they are very rarely associated with neoplasia or cancer in the general population, and cause lenient warts. Other HPVs are considered as high-risk types because they are responsible for several important human cancers, including cervical cancer, a large proportion of other anogenital cancers, and a growing number of head and neck cancers. Transmission of HPV occurs primarily by skin-to-skin contact. The risk of contracting genital HPV infection and cervical cancer is influenced by sexual activity. Currently two prophylactic HPV vaccines, Gardasil® (Merck, USA) and Cervarix® (GlaxoSmithKline, UK), are available and recommended for mass immunization of adolescents. However, these vaccines have limitations as they are expensive and require cold chain storage and trained personnel to administer them by injection. The use of nano or micro particulate vaccines could address most of these limitations as they are stable at room temperature, inexpensive to produce and distribute to resource poor regions, and can be administered orally without the need for adjuvants in the formulation. Also it is possible to increase the efficiency of these particulate vaccines by decorating the surface of the nano or micro particulates with suitable ligands for targeted delivery. Oral vaccines, which can be delivered using particulate formulations, have the added potential to stimulate mucosa-associated lymphoid tissue located in the digestive tract and the gut-associated lymphoid tissue, both of which are important for the induction of effective mucosal response against many viruses. In addition, oral vaccines provide the opportunity to reduce production and administration costs and are very patient compliant. This review elaborately discusses different strategies that can be pursued to develop a nano or micro particulate oral vaccine for HPV induced cancers and

  2. Cancer Vaccines

    Science.gov (United States)

    ... Cervical Cancer Solid Tumors Selected References Pardoll D. Cancer immunology. In: Abeloff M, Armitage J, Niederhuber J, Kastan ... 178(4):1975–1979. [PubMed Abstract] Finn OJ. Cancer immunology. New England Journal of Medicine 2008;358(25): ...

  3. Cervical cancer vaccine: Exploring new opportunities and challenges for developing countries

    Directory of Open Access Journals (Sweden)

    Ananya Ray Laskar

    2011-01-01

    Full Text Available Cervical cancer is the second most common cancer in women worldwide, and the burden of the disease is disproportionately high in the developing world (>80%. With the advent of two new vaccines, "Gardasil" developed by Merck & Co. New Jersey, USA and "Cervarix" developed by GlaxoSmithKline (GSK in Philadelphia, USA, the future holds newer promises for prevention and control of the disease. However, various regulatory and policy changes also may be required to be undertaken and the various new challenges need to be addressed.

  4. Development of an autologous canine cancer vaccine system for resectable malignant tumors in dogs.

    Science.gov (United States)

    Yannelli, J R; Wouda, R; Masterson, T J; Avdiushko, M G; Cohen, D A

    2016-12-01

    While conventional therapies exist for canine cancer, immunotherapies need to be further explored and applied to the canine setting. We have developed an autologous cancer vaccine (K9-ACV), which is available for all dogs with resectable disease. K9-ACV was evaluated for safety and immunogenicity for a variety of cancer types in a cohort of companion dogs under veterinary care. The autologous vaccine was prepared by enzymatic digestion of solid tumor biopsies. The resultant single cell suspensions were then UV-irradiated resulting in immunogenic cell death of the tumor cells. Following sterility and endotoxin testing, the tumor cells were admixed with CpG ODN adjuvant and shipped to the participating veterinary clinics. The treating veterinarians then vaccinated each patient with three intradermal injections (10 million cells per dose) at 30-day intervals (one prime and two boost injections). In a cohort of 20 dogs completing the study, 17 dogs (85%) developed an augmented IgG response to autologous tumor antigens as demonstrated using western blot analysis of pre- and post-peripheral blood samples. We also report several dogs have lived beyond expected survival time based on previously published data. In summary, K9-ACV is an additional option to be considered for the treatment of dogs with resectable cancer.

  5. Cellular based cancer vaccines

    DEFF Research Database (Denmark)

    Hansen, Morten; Met, O; Svane, I M;

    2012-01-01

    Cancer vaccines designed to re-calibrate the existing host-tumour interaction, tipping the balance from tumor acceptance towards tumor control holds huge potential to complement traditional cancer therapies. In general, limited success has been achieved with vaccines composed of tumor...... in vitro migration via autocrine receptor-mediated endocytosis of CCR7. In the current review, we discuss optimal design of DC maturation focused on pre-clinical as well as clinical results from standard and polarized dendritic cell based cancer vaccines....

  6. Realizing the promise of breast cancer vaccines

    Directory of Open Access Journals (Sweden)

    Jackson E

    2012-08-01

    Full Text Available Erica Jackson, Hatem SolimanUniversity of South Florida/Moffitt Cancer Center and Research Institute, Tampa, FL, USAAbstract: Breast cancer vaccines are being developed to stimulate adaptive antitumor immune responses in patients. These vaccines have the potential to treat breast cancer with minimal side effects and toxicity. However, many obstacles still need to be overcome to fully realize the vaccines' clinical benefit. A review of the literature was conducted to assess the use of vaccines in targeting transformed cells. Four vaccines currently under study were discussed, each summarizing the different vaccine platforms used to introduce target antigen to the patient's immune system. The advantages and disadvantages of each method were discussed, although no one method was found to be superior. Additional issues addressed included overcoming tumor-induced immunosuppression, immune evasion of transformed cells, the use of vaccines in combination therapy, and the challenges of using these vaccines in various clinical settings. Vaccines may be most effective in patients with minimal residual disease, as opposed to using them in the metastatic setting. Also, specific clinical trial design considerations for the use of vaccines in cancer patients, such as time-to-failure end points, were discussed. Understanding these various elements will be important to the translation of breast cancer vaccine therapy into routine clinical practice.Keywords: breast cancer, vaccine, immunotherapy, immune tolerance, peptide vaccine, dendritic cell vaccine

  7. Alpha fetoprotein is more than a hepatocellular cancer biomarker: from spontaneous immune response in cancer patients to the development of an AFP-based cancer vaccine.

    Science.gov (United States)

    Bei, R; Mizejewski, G J

    2011-10-01

    Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide, with a poor prognosis and limited therapeutic options. Due to its overexpression in the majority of HCCs, alpha-fetoprotein (AFP) represents one of the most useful markers for hepatocarcinomas and for monitoring patients' response to therapy. Although it was earlier reported that AFP has immunosuppressive properties, it has been recently demonstrated that AFP induces spontaneous T and B cells responses in HCC patients. The characterization of AFP-immunogenic epitopes gives the opportunity to design AFP-based cancer vaccines for human HCC. The activity of AFP-based vaccines has been investigated in HCC mouse models in order to develop novel strategies to treat patients with HCC. This review will discuss the rationale for using the AFP-based vaccination strategy and recent results corroborating the usefulness of AFP vaccines as a potential tool for cancer therapy.

  8. 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......-delineation applies to cancer vaccine responses. T cell clones were generated from all nine patients studied. We find that surviving patients harbor durable tumor-specific responses against vaccine antigens from telomerase, RAS or TGFbeta receptor II. Analyses of consecutive samples suggest that booster...

  9. 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

    Immunotherapy against cancer has shown increased overall survival of metastatic cancer patients and is a promising new vaccine target. For this to succeed, appropriate tailoring of vaccine formulations to mount in vivo cytotoxic T cell (CTL) responses towards co-delivered cancer antigens...... 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...

  10. 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

  11. Guidance for peptide vaccines for the treatment of cancer

    OpenAIRE

    Yamaguchi, Yoshiyuki; Yamaue, Hiroki; Okusaka, Takuji; Okuno, Kiyotaka; Suzuki, Hiroyuki; Fujioka, Tomoaki; Otsu, Atsushi; Ohashi, Yasuo; Shimazawa, Rumiko; Nishio, Kazuto; Furuse, Junji; Minami, Hironobu; Tsunoda, Takuya; Hayashi, Yuzo; Nakamura, Yusuke

    2014-01-01

    Recent progress in fundamental understanding of tumor immunology has opened a new avenue of cancer vaccines. Currently, the development of new cancer vaccines is a global topic and has attracted attention as one of the most important issues in Japan. There is an urgent need for the development of guidance for cancer vaccine clinical studies in order to lead to drug development. Peptide vaccines characteristically have the effect of indirectly acting against cancer through the immune system – ...

  12. Immunosuppressive networks and checkpoints controlling antitumor immunity and their blockade in the development of cancer immunotherapeutics and vaccines.

    Science.gov (United States)

    Butt, A Q; Mills, K H G

    2014-09-18

    Vaccines that promote protective adaptive immune responses have been successfully developed against a range of infectious diseases, and these are normally administered prior to exposure with the relevant virus or bacteria. Adaptive immunity also plays a critical role in the control of tumors. Immunotherapeutics and vaccines that promote effector T cell responses have the potential to eliminate tumors when used in a therapeutic setting. However, the induction of protective antitumor immunity is compromised by innate immunosuppressive mechanisms and regulatory cells that often dominate the tumor microenvironment. Recent studies have shown that blocking these suppressor cells and immune checkpoints to allow induction of antitumor immunity is a successful immunotherapeutic modality for the treatment of cancer. Furthermore, stimulation of innate and consequently adaptive immune responses with concomitant inhibition of immune suppression, especially that mediated by regulatory T (Treg) cells, is emerging as a promising approach to enhance the efficacy of therapeutic vaccines against cancer. This review describes the immunosuppressive mechanisms controlling antitumor immunity and the novel strategies being employed to design effective immunotherapeutics against tumors based on inhibition of suppressor cells or blockade of immune checkpoints to allow induction of more potent effector T cell responses. This review also discusses the potential of using a combination of adjuvants with inhibition of immune checkpoint or suppressor cells for therapeutic vaccines and the translation of pre-clinical studies to the next-generation vaccines against cancer in humans.

  13. Therapeutic Vaccination for HPV Induced Cervical Cancers

    Directory of Open Access Journals (Sweden)

    Joeli A. Brinkman

    2007-01-01

    Full Text Available Cervical Cancer is the second leading cause of cancer–related deaths in women worldwide and is associated with Human Papillomavirus (HPV infection, creating a unique opportunity to treat cervical cancer through anti-viral vaccination. Although a prophylactic vaccine may be available within a year, millions of women, already infected, will continue to suffer from HPV-related disease, emphasizing the need to develop therapeutic vaccination strategies. A majority of clinical trials examining therapeutic vaccination have shown limited efficacy due to examining patients with more advanced-stage cancer who tend to have decreased immune function. Current trends in clinical trials with therapeutic agents examine patients with pre-invasive lesions in order to prevent invasive cervical cancer. However, longer follow-up is necessary to correlate immune responses to lesion regression. Meanwhile, preclinical studies in this field include further exploration of peptide or protein vaccination, and the delivery of HPV antigens in DNA-based vaccines or in viral vectors. As long as pre-clinical studies continue to advance, the prospect of therapeutic vaccination to treat existing lesions seem good in the near future. Positive consequences of therapeutic vaccination would include less disfiguring treatment options and fewer instances of recurrent or progressive lesions leading to a reduction in cervical cancer incidence.

  14. Peptide Vaccine Therapy in Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Shi-Yu Yang

    2012-08-01

    Full Text Available Colorectal cancer is the third most common cause of cancer-related deaths and the second most prevalent (after breast cancer in the western world. High metastatic relapse rates and severe side effects associated with the adjuvant treatment have urged oncologists and clinicians to find a novel, less toxic therapeutic strategy. Considering the limited success of the past clinical trials involving peptide vaccine therapy to treat colorectal cancer, it is necessary to revise our knowledge of the immune system and its potential use in tackling cancer. This review presents the efforts of the scientific community in the development of peptide vaccine therapy for colorectal cancer. We review recent clinical trials and the strategies for immunologic monitoring of responses to peptide vaccine therapy. We also discuss the mechanisms underlying the therapy and potential molecular targets in colon cancer.

  15. Preventing Cervical Cancer with HPV Vaccines

    Science.gov (United States)

    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.

  16. Dengue virus vaccine development.

    Science.gov (United States)

    Yauch, Lauren E; Shresta, Sujan

    2014-01-01

    Dengue virus (DENV) is a significant cause of morbidity and mortality in tropical and subtropical regions, causing hundreds of millions of infections each year. Infections range from asymptomatic to a self-limited febrile illness, dengue fever (DF), to the life-threatening dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). The expanding of the habitat of DENV-transmitting mosquitoes has resulted in dramatic increases in the number of cases over the past 50 years, and recent outbreaks have occurred in the United States. Developing a dengue vaccine is a global health priority. DENV vaccine development is challenging due to the existence of four serotypes of the virus (DENV1-4), which a vaccine must protect against. Additionally, the adaptive immune response to DENV may be both protective and pathogenic upon subsequent infection, and the precise features of protective versus pathogenic immune responses to DENV are unknown, complicating vaccine development. Numerous vaccine candidates, including live attenuated, inactivated, recombinant subunit, DNA, and viral vectored vaccines, are in various stages of clinical development, from preclinical to phase 3. This review will discuss the adaptive immune response to DENV, dengue vaccine challenges, animal models used to test dengue vaccine candidates, and historical and current dengue vaccine approaches.

  17. Development of InCVAX as a novel in situ autologous vaccine for metastatic cancers (Conference Presentation)

    Science.gov (United States)

    Hode, Tomas; Alleruzzo, Luciano; Raker, Joseph; Lam, Samuel Siu Kit; Nordquist, Robert E.; Chen, Wei R.

    2016-03-01

    A novel method, an in situ autologous whole-cell cancer vaccine (inCVAX), is being developed by Immunophotonics, Inc., for the treatment of metastatic cancers. inCVAX combines phototherapy and immunotherapy to potentially induce a systemic anti-tumor immune response in the hosts. Immunophotonics and its academic partners have spent years conducting nonclinical research, developing CMC techniques and conducting clinical research. In 2015 the company initiated a late-stage (II/III) clinical trial in South America for advanced breast cancer patients. The process of developing the inCVAX approach from a laboratory setting into clinical trials requires significant efforts from a group of dedicated engineers, scientists, and physicians. The growth of the company and its business advances demonstrated the determination of a group of visionary investors, entrepreneurs, and business leaders. This talk will chronicle the milestones of the scientific achievement, medical progress, and business development of Immunophotonics.

  18. Therapeutic cancer vaccines and combination immunotherapies involving vaccination

    Directory of Open Access Journals (Sweden)

    Nguyen T

    2014-10-01

    Full Text Available Trang Nguyen,1 Julie Urban,1 Pawel Kalinski1–5 1Department of Surgery, 2Department of Immunology, 3Department of Microbiology and Infectious Disease, 4Department of Bioengineering, University of Pittsburgh, 5University of Pittsburgh Cancer Institute, Pittsburgh, PA, USAAbstract: Recent US Food and Drug Administration approvals of Provenge® (sipuleucel-T as the first cell-based cancer therapeutic factor and ipilimumab (Yervoy®/anticytotoxic T-lymphocyte antigen-4 as the first “checkpoint blocker” highlight recent advances in cancer immunotherapy. Positive results of the clinical trials evaluating additional checkpoint blocking agents (blockade of programmed death [PD]-1, and its ligands, PD-1 ligand 1 and 2 and of several types of cancer vaccines suggest that cancer immunotherapy may soon enter the center stage of comprehensive cancer care, supplementing surgery, radiation, and chemotherapy. This review discusses the current status of the clinical evaluation of different classes of therapeutic cancer vaccines and possible avenues for future development, focusing on enhancing the magnitude and quality of cancer-specific immunity by either the functional reprogramming of patients' endogenous dendritic cells or the use of ex vivo-manipulated dendritic cells as autologous cellular transplants. This review further discusses the available strategies aimed at promoting the entry of vaccination-induced T-cells into tumor tissues and prolonging their local antitumor activity. Finally, the recent improvements to the above three modalities for cancer immunotherapy (inducing tumor-specific T-cells, prolonging their persistence and functionality, and enhancing tumor homing of effector T-cells and rationale for their combined application in order to achieve clinically effective anticancer responses are addressed.Keywords: immunotherapy, cancer, vaccines

  19. Development of an oral DNA vaccine against MG7-Ag of gastric cancer using attenuated salmonella typhimurium as carrier

    Institute of Scientific and Technical Information of China (English)

    Chang-Cun Guo; Jie Ding; Bo-Rong Pan; Zhao-Cai Yu; Quan-Li Han; Fan-Ping Meng; Na Liu; Dai-Ming Fan

    2003-01-01

    AIM: To develop an oral DNA vaccine against gastric cancer and evaluate its efficacy in mice.METHODS: The genes of the MG7-Ag mimotope and a universal Th epitope (Pan-DR epitope, PADRE) were included in the PCR primers. By PCR, the fusion gene of the two epitopes was amplified. The fusion gene was confirmed by sequencing and was then cloned into pcDNA3.1(+) plasmid. The pcDNA3.1 (+)-MG7/PADRE was used to transfect an attenuated Salrmonella typhimuriurm.C57BL/6 mice were orally immunized with 1x108 cfu Salrmonella transfectants. Salmonella harboring the empty pcDNA3.1(+) plasmid and phosphate buffer saline (PBS)were used as negative controls. At the 6th week, serum titer of MG7-Ag specific antibody was detected by ELtSA.At the 8th week cellular immunity was detected by an unprimed proliferation test of the spleenocytes by using a [3H]-thymidine incorporation assay. Ehrlich ascites carcinoma cells expressing MG7-Ag were used as a model in tumor challenge assay to evaluate the protective effect of the vaccine.RESULTS: Serum titer of antibody against MG7-Ag was significantly higher in mice immunized with the vaccine than that in control groups (0.841 vs 0.347, P<0.01; 0.841 vs 0.298,P<0.01), while in vitro unprimed proliferation assay of the spleenocytes showed no statistical difference between those three groups. Two weeks after tumor challenge, 2 in 7 immunized mice were tumor free, while all the mice in the control groups showed tumor formation. CONCLUSION: Oral DNA vaccine against the MG7-Ag momitope of gastric cancer is immunogenic. It can induce significant humoral immunity against tumor in mice, and the vaccine has partially protective effects.

  20. Developing vaccines against pandemic influenza.

    OpenAIRE

    Wood, J M

    2001-01-01

    Pandemic influenza presents special problems for vaccine development. There must be a balance between rapid availability of vaccine and the safeguards to ensure safety, quality and efficacy of vaccine. Vaccine was developed for the pandemics of 1957, 1968, 1977 and for the pandemic alert of 1976. This experience is compared with that gained in developing vaccines for a possible H5N1 pandemic in 1997-1998. Our ability to mass produce influenza vaccines against a pandemic threat was well illust...

  1. RNA-Based Vaccines in Cancer Immunotherapy.

    Science.gov (United States)

    McNamara, Megan A; Nair, Smita K; Holl, Eda K

    2015-01-01

    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.

  2. RNA-Based Vaccines in Cancer Immunotherapy

    Directory of Open Access Journals (Sweden)

    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.

  3. Cancer vaccines: the perspective of the Cancer Immunology Branch, NCI.

    Science.gov (United States)

    Sogn, J A; Finerty, J F; Heath, A K; Shen, G L; Austin, F C

    1993-08-12

    The Cancer Immunology Branch, NCI, is supporting a great deal of exciting research relevant to cancer vaccine development. The few areas highlighted here are representative of ongoing research opportunities, but further progress depends largely on a continued infusion of investigator-initiated ideas to realize the potential of current research areas and open new ones.

  4. Clinical development of Ebola vaccines.

    Science.gov (United States)

    Sridhar, Saranya

    2015-09-01

    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.

  5. Development of a next generation Semliki Forest virus-based DNA vaccine against cervical cancer

    NARCIS (Netherlands)

    Van De Wall, Stephanie; Ljungberg, Karl; Peng IP, Peng; Boerma, Annemarie; Nijman, Hans W.; Liljeström, Peter; Daemen, Toos

    2014-01-01

    Cervical cancer is the second most prevalent cancer among women worldwide. The disease develops as a result of infection with high-risk human papillomavirus (HPV) through persistent expression of early proteins E6 and E7 with transforming capacities in cervical epithelial cells. Our group pioneered

  6. Development of therapeutic HPV vaccines

    OpenAIRE

    Trimble, Cornelia L.; Frazer, Ian H

    2009-01-01

    At least 15% of human malignant diseases are attributable to the consequences of persistent viral or bacterial infection. Chronic infection with oncogenic human papillomavirus (HPV) types is a necessary, but insufficient, cause in the development of more cancers than any other virus. Currently available prophylactic vaccines have no therapeutic effect for established infection or for disease. Early disease is characterised by tissue sequestration. However, because a proportion of intraepithel...

  7. Risk in vaccine research and development quantified.

    Directory of Open Access Journals (Sweden)

    Esther S Pronker

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

  8. Dendritic Cell Cancer Vaccines: From the Bench to the Bedside

    Directory of Open Access Journals (Sweden)

    Tamar Katz

    2014-10-01

    Full Text Available The recognition that the development of cancer is associated with acquired immunodeficiency, mostly against cancer cells themselves, and understanding pathways inducing this immunosuppression, has led to a tremendous development of new immunological approaches, both vaccines and drugs, which overcome this inhibition. Both “passive” (e.g. strategies relying on the administration of specific T cells and “active” vaccines (e.g. peptide-directed or whole-cell vaccines have become attractive immunological approaches, inducing cell death by targeting tumor-associated antigens. Whereas peptide-targeted vaccines are usually directed against a single antigen, whole-cell vaccines (e.g. dendritic cell vaccines are aimed to induce robust responsiveness by targeting several tumor-related antigens simultaneously. The combination of vaccines with new immuno-stimulating agents which target “immunosuppressive checkpoints” (anti-CTLA-4, PD-1, etc. is likely to improve and maintain immune response induced by vaccination.

  9. 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;

    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...... superior to rodents as they are more closely related to humans in terms of immunology and physiology. Here, we introduce pigs as a supplementary large animal model for human cancer vaccine development via the use of our unique technology for swine leukocyte antigen (SLA) production. IDO and RhoC, two tumor...... antigens previously identified as important players in human cancer development and progression, were used as vaccine targets. Using peptide-MHC-I binding predictors we identified IDO-derived and RhoC-derived candidate peptides potentially binding to five different broadly distributed SLA molecules. We...

  10. Cancer Vaccines in Ovarian Cancer: How Can We Improve?

    Directory of Open Access Journals (Sweden)

    Silvia Martin Lluesma

    2016-05-01

    Full Text Available Epithelial ovarian cancer (EOC is one important cause of gynecologic cancer-related death. Currently, the mainstay of ovarian cancer treatment consists of cytoreductive surgery and platinum-based chemotherapy (introduced 30 years ago but, as the disease is usually diagnosed at an advanced stage, its prognosis remains very poor. Clearly, there is a critical need for new treatment options, and immunotherapy is one attractive alternative. Prophylactic vaccines for prevention of infectious diseases have led to major achievements, yet therapeutic cancer vaccines have shown consistently low efficacy in the past. However, as they are associated with minimal side effects or invasive procedures, efforts directed to improve their efficacy are being deployed, with Dendritic Cell (DC vaccination strategies standing as one of the more promising options. On the other hand, recent advances in our understanding of immunological mechanisms have led to the development of successful strategies for the treatment of different cancers, such as immune checkpoint blockade strategies. Combining these strategies with DC vaccination approaches and introducing novel combinatorial designs must also be considered and evaluated. In this review, we will analyze past vaccination methods used in ovarian cancer, and we will provide different suggestions aiming to improve their efficacy in future trials.

  11. An autoimmune-mediated strategy for prophylactic breast cancer vaccination.

    Science.gov (United States)

    Jaini, Ritika; Kesaraju, Pavani; Johnson, Justin M; Altuntas, Cengiz Z; Jane-Wit, Daniel; Tuohy, Vincent K

    2010-07-01

    Although vaccination is most effective when used to prevent disease, cancer vaccine development has focused predominantly on providing therapy against established growing tumors. The difficulty in developing prophylactic cancer vaccines is primarily due to the fact that tumor antigens are variations of self proteins and would probably mediate profound autoimmune complications if used in a preventive vaccine setting. Here we use several mouse breast cancer models to define a prototypic strategy for prophylactic cancer vaccination. We selected alpha-lactalbumin as our target vaccine autoantigen because it is a breast-specific differentiation protein expressed in high amounts in the majority of human breast carcinomas and in mammary epithelial cells only during lactation. We found that immunoreactivity against alpha-lactalbumin provides substantial protection and therapy against growth of autochthonous tumors in transgenic mouse models of breast cancer and against 4T1 transplantable breast tumors in BALB/c mice. Because alpha-lactalbumin is conditionally expressed only during lactation, vaccination-induced prophylaxis occurs without any detectable inflammation in normal nonlactating breast tissue. Thus, alpha-lactalbumin vaccination may provide safe and effective protection against the development of breast cancer for women in their post-child-bearing, premenopausal years, when lactation is readily avoidable and risk for developing breast cancer is high.

  12. Improvement of different vaccine delivery systems for cancer therapy

    Directory of Open Access Journals (Sweden)

    Safaiyan Shima

    2011-01-01

    Full Text Available Abstract Cancer vaccines are the promising tools in the hands of the clinical oncologist. Many tumor-associated antigens are excellent targets for immune therapy and vaccine design. Optimally designed cancer vaccines should combine the best tumor antigens with the most effective immunotherapy agents and/or delivery strategies to achieve positive clinical results. Various vaccine delivery systems such as different routes of immunization and physical/chemical delivery methods have been used in cancer therapy with the goal to induce immunity against tumor-associated antigens. Two basic delivery approaches including physical delivery to achieve higher levels of antigen production and formulation with microparticles to target antigen-presenting cells (APCs have demonstrated to be effective in animal models. New developments in vaccine delivery systems will improve the efficiency of clinical trials in the near future. Among them, nanoparticles (NPs such as dendrimers, polymeric NPs, metallic NPs, magnetic NPs and quantum dots have emerged as effective vaccine adjuvants for infectious diseases and cancer therapy. Furthermore, cell-penetrating peptides (CPP have been known as attractive carrier having applications in drug delivery, gene transfer and DNA vaccination. This review will focus on the utilization of different vaccine delivery systems for prevention or treatment of cancer. We will discuss their clinical applications and the future prospects for cancer vaccine development.

  13. Nanotechnology and vaccine development

    Directory of Open Access Journals (Sweden)

    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.

  14. Swine flu vaccination for patients with cancers

    Directory of Open Access Journals (Sweden)

    Viroj Wiwanitkit

    2011-01-01

    Full Text Available In oncology, vaccination is accepted as an important preventive measure. As a tertiary prevention protocol, several vaccines are recommended for the oncology patients. The newest vaccine in medicine is swine flu vaccine which is developed for prevention of novel H1N1 influenza virus infection. In this paper, the author will briefly discuss on swine flu vaccination for oncology patients.

  15. Clinical Impact of Vaccine Development.

    Science.gov (United States)

    Nambiar, Puja H; Daza, Alejandro Delgado; Livornese, Lawrence L

    2016-01-01

    The discovery and development of immunization has been a singular improvement in the health of mankind. This chapter reviews currently available vaccines, their historical development, and impact on public health. Specific mention is made in regard to the challenges and pursuit of a vaccine for the human immunodeficiency virus as well as the unfounded link between autism and measles vaccination.

  16. 肿瘤疫苗研发进展%Progress in the Research and Development of Cancer Vaccines

    Institute of Scientific and Technical Information of China (English)

    李扬; 王敏; 孙晓北; 郭柯磊; 池慧

    2013-01-01

    In this paper, we analyzed cancer vaccine targets, R&D status and patents based on literatures re⁃trieved from Thomson Reuters Pharma Database, Integrity Database and Derwent Innovation Index Database. To keep up with global R&D priorities in cancer vaccines so as to provide background information for R&D of can⁃cer vaccine in China.%  通过检索 Thomson Reuters Pharma 数据库、Integrity 数据库和 Derwent Innovation Index 数据库,对肿瘤疫苗的研发技术靶点、研发状态、有关专利进行分析,把握国际肿瘤疫苗的技术研发重点领,为我国肿瘤疫苗研发发展提供信息据。

  17. The application of exosomes as a nanoscale cancer vaccine

    Directory of Open Access Journals (Sweden)

    Aaron Tan

    2010-11-01

    Full Text Available Aaron Tan1, Hugo De La Peña2, Alexander M Seifalian1,31UCL Division of Surgery and Interventional Science, Centre for Nanotechnology and Regenerative Medicine, University College London, London, UK; 2Department of Pathology, University of Cambridge, Cambridge, UK; 3Royal Free Hampstead NHS Trust Hospital, London, UKAbstract: Cancer is a leading cause of death globally, and it is predicted and projected to continue rising as life expectancy increases. Although patient survival rates for some forms of cancers are high due to clinical advances in treatment protocols, the search for effective cancer vaccines remains the ultimate Rosetta Stone in oncology. Cervarix®, Gardasil®, and hepatitis B vaccines are currently employed in preventing certain forms of viral cancers. However, they are, strictly speaking, not ‘true’ cancer vaccines as they are prophylactic rather than therapeutic, are only effective against the oncogenic viruses, and do not kill the actual cancer cells. On April 2010, a new prostate cancer vaccine Provenge® (sipuleucel-T was approved by the US FDA, and it is the first approved therapeutic vaccine that utilizes antigen-presenting cell technology involving dendritic cells in cancer immunotherapy. Recent evidence suggests that the use of nanoscale particles like exosomes in immunotherapy could form a viable basis for the development of novel cancer vaccines, via antigen-presenting cell technology, to prime the immune system to recognize and kill cancer cells. Coupled with nanotechnology, engineered exosomes are emerging as new and novel avenues for cancer vaccine development. Here, we review the current knowledge pertaining to exosome technology in immunotherapy and also seek to address the challenges and future directions associated with it, in hopes of bringing this exciting application a step closer toward an effective clinical reality.Keywords: exosomes, cancer vaccine, immunotherapy, nanomedicine 

  18. NIH Research Leads to Cervical Cancer Vaccine

    Science.gov (United States)

    ... Current Issue Past Issues Sexually Transmitted Diseases NIH Research Leads to Cervical Cancer Vaccine Past Issues / Fall 2008 Table of Contents For ... mystery. Most important, however, is to have a vaccine which potentially can ... focusing their research on helping to produce second-generation HPV vaccines ...

  19. Emerging Cancer Vaccines: The Promise of Genetic Vectors

    Energy Technology Data Exchange (ETDEWEB)

    Aurisicchio, Luigi, E-mail: aurisicchio@takis-it.it [Takis, via di Castel Romano 100, 00128 Rome (Italy); BIOGEM scarl, via Camporeale, 83031 Ariano Irpino (AV) (Italy); Ciliberto, Gennaro [Takis, via di Castel Romano 100, 00128 Rome (Italy); Dipartimento di Medicina Sperimentale e Clinica, Università degli studi di Catanzaro “Magna Graecia”, 88100 Catanzaro (Italy)

    2011-09-22

    Therapeutic vaccination against cancer is an important approach which, when combined with other therapies, can improve long-term control of cancer. In fact, the induction of adaptive immune responses against Tumor Associated Antigens (TAAs) as well as innate immunity are important factors for tumor stabilization/eradication. A variety of immunization technologies have been explored in last decades and are currently under active evaluation, such as cell-based, protein, peptide and heat-shock protein-based cancer vaccines. Genetic vaccines are emerging as promising methodologies to elicit immune responses against a wide variety of antigens, including TAAs. Amongst these, Adenovirus (Ad)-based vectors show excellent immunogenicity profile and have achieved immunological proof of concept in humans. In vivo electroporation of plasmid DNA (DNA-EP) is also a desirable vaccine technology for cancer vaccines, as it is repeatable several times, a parameter required for the long-term maintenance of anti-tumor immunity. Recent findings show that combinations of different modalities of immunization (heterologous prime/boost) are able to induce superior immune reactions as compared to single-modality vaccines. In this review, we will discuss the challenges and requirements of emerging cancer vaccines, particularly focusing on the genetic cancer vaccines currently under active development and the promise shown by Ad and DNA-EP heterologous prime-boost.

  20. Emerging Cancer Vaccines: The Promise of Genetic Vectors

    Directory of Open Access Journals (Sweden)

    Gennaro Ciliberto

    2011-09-01

    Full Text Available Therapeutic vaccination against cancer is an important approach which, when combined with other therapies, can improve long-term control of cancer. In fact, the induction of adaptive immune responses against Tumor Associated Antigens (TAAs as well as innate immunity are important factors for tumor stabilization/eradication. A variety of immunization technologies have been explored in last decades and are currently under active evaluation, such as cell-based, protein, peptide and heat-shock protein-based cancer vaccines. Genetic vaccines are emerging as promising methodologies to elicit immune responses against a wide variety of antigens, including TAAs. Amongst these, Adenovirus (Ad-based vectors show excellent immunogenicity profile and have achieved immunological proof of concept in humans. In vivo electroporation of plasmid DNA (DNA-EP is also a desirable vaccine technology for cancer vaccines, as it is repeatable several times, a parameter required for the long-term maintenance of anti-tumor immunity. Recent findings show that combinations of different modalities of immunization (heterologous prime/boost are able to induce superior immune reactions as compared to single-modality vaccines. In this review, we will discuss the challenges and requirements of emerging cancer vaccines, particularly focusing on the genetic cancer vaccines currently under active development and the promise shown by Ad and DNA-EP heterologous prime-boost.

  1. Generation of more effective cancer vaccines

    Science.gov (United States)

    Fenoglio, Daniela; Traverso, Paolo; Parodi, Alessia; Kalli, Francesca; Zanetti, Maurizio; Filaci, Gilberto

    2013-01-01

    Cancer vaccines represent a promising therapeutic approach for which prime time is imminent. However, clinical efficacy must be improved in order for cancer vaccines to become a valid alternative or complement to traditional cancer treatments. Considerable efforts have been undertaken so far to better understand the fundamental requirements for clinically-effective cancer vaccines. Recent data emphasize that important requirements, among others, are (1) the use of multi-epitope immunogens, possibly deriving from different tumor antigens; (2) the selection of effective adjuvants; (3) the association of cancer vaccines with agents able to counteract the regulatory milieu present in the tumor microenvironment; and (4) the need to choose the definitive formulation and regimen of a vaccine after accurate preliminary tests comparing different antigen formulations. The first requirement deals with issues related to HLA restriction of tumor antigen presentation, as well as usefulness of tumor antigen spreading and counteraction of immune escape phenomena, linked to tumor antigen down-modulation, for an effective anti-cancer immune response. The second point underscores the necessity of optimal activation of innate immunity to achieve an efficient adaptive anti-cancer immune response. The third point focuses on the importance to inhibit subsets of regulatory cells. The last requirement stresses the concept that the regimen and formulation of the vaccine impacts profoundly on cancer vaccine efficacy. A new generation of cancer vaccines, provided with both immunological and clinical efficacy, will hopefully soon address these requirements. PMID:23978951

  2. Immune Modulation by Chemotherapy or Immunotherapy to Enhance Cancer Vaccines

    Directory of Open Access Journals (Sweden)

    Marc Mansour

    2011-08-01

    Full Text Available Chemotherapy has been a mainstay in cancer treatment for many years. Despite some success, the cure rate with chemotherapy remains unsatisfactory in some types of cancers, and severe side effects from these treatments are a concern. Recently, understanding of the dynamic interplay between the tumor and immune system has led to the development of novel immunotherapies, including cancer vaccines. Cancer vaccines have many advantageous features, but their use has been hampered by poor immunogenicity. Many developments have increased their potency in pre-clinical models, but cancer vaccines continue to have a poor clinical track record. In part, this could be due to an inability to effectively overcome tumor-induced immune suppression. It had been generally assumed that immune-stimulatory cancer vaccines could not be used in combination with immunosuppressive chemotherapies, but recent evidence has challenged this dogma. Chemotherapies could be used to condition the immune system and tumor to create an environment where cancer vaccines have a better chance of success. Other types of immunotherapies could also be used to modulate the immune system. This review will discuss how immune modulation by chemotherapy or immunotherapy could be used to bolster the effects of cancer vaccines and discuss the advantages and disadvantages of these treatments.

  3. Immune Modulation by Chemotherapy or Immunotherapy to Enhance Cancer Vaccines

    Energy Technology Data Exchange (ETDEWEB)

    Weir, Genevieve M. [Suite 411, 1344 Summer St., Immunovaccine Inc., Halifax, NS, B3H 0A8 (Canada); Room 11-L1, Sir Charles Tupper Building, Department of Microbiology & Immunology, Dalhousie University, 5850 College St, Halifax, NS, B3H 1X5 (Canada); Liwski, Robert S. [Room 11-L1, Sir Charles Tupper Building, Department of Microbiology & Immunology, Dalhousie University, 5850 College St, Halifax, NS, B3H 1X5 (Canada); Room 206E, Dr. D. J. Mackenzie Building, Department of Pathology, Dalhousie University, 5788 University Avenue, Halifax, NS, B3H 2Y9 (Canada); Mansour, Marc [Suite 411, 1344 Summer St., Immunovaccine Inc., Halifax, NS, B3H 0A8 (Canada)

    2011-08-05

    Chemotherapy has been a mainstay in cancer treatment for many years. Despite some success, the cure rate with chemotherapy remains unsatisfactory in some types of cancers, and severe side effects from these treatments are a concern. Recently, understanding of the dynamic interplay between the tumor and immune system has led to the development of novel immunotherapies, including cancer vaccines. Cancer vaccines have many advantageous features, but their use has been hampered by poor immunogenicity. Many developments have increased their potency in pre-clinical models, but cancer vaccines continue to have a poor clinical track record. In part, this could be due to an inability to effectively overcome tumor-induced immune suppression. It had been generally assumed that immune-stimulatory cancer vaccines could not be used in combination with immunosuppressive chemotherapies, but recent evidence has challenged this dogma. Chemotherapies could be used to condition the immune system and tumor to create an environment where cancer vaccines have a better chance of success. Other types of immunotherapies could also be used to modulate the immune system. This review will discuss how immune modulation by chemotherapy or immunotherapy could be used to bolster the effects of cancer vaccines and discuss the advantages and disadvantages of these treatments.

  4. Military Infectious Diseases Update on Vaccine Development

    Science.gov (United States)

    2011-01-24

    development thrusts • Enterotoxigenic Escherichia coli (ETEC) vaccines • Shigella vaccines • Campylobacter jejuni vaccines 2011 MHS Conference Vaccines...Injectisome extending from Shigella Injectisome Injectisome graphic 2011 MHS Conference  Campylobacter jejuni – Transmission: Foodborne – Inoculum

  5. Development of dengue DNA vaccines.

    Science.gov (United States)

    Danko, Janine R; Beckett, Charmagne G; Porter, Kevin R

    2011-09-23

    Vaccination with plasmid DNA against infectious pathogens including dengue is an active area of investigation. By design, DNA vaccines are able to elicit both antibody responses and cellular immune responses capable of mediating long-term protection. Great technical improvements have been made in dengue DNA vaccine constructs and trials are underway to study these in the clinic. The scope of this review is to highlight the rich history of this vaccine platform and the work in dengue DNA vaccines accomplished by scientists at the Naval Medical Research Center. This work resulted in the only dengue DNA vaccine tested in a clinical trial to date. Additional advancements paving the road ahead in dengue DNA vaccine development are also discussed.

  6. Infections and cancer: debate about using vaccines as a cancer control tool.

    Science.gov (United States)

    Mbulaiteye, Sam M; Buonaguro, Franco M

    2013-05-04

    In 2012, Infectious Agents and Cancer commissioned a thematic series collection of articles on Prevention of HPV related cancer. The articles have attracted wide interest and stimulated debate, including about the utility of vaccines in cancer control. The application of vaccines to cancer control fulfills a promise envisioned at the turn of the 20th century when remarkable experiments showed that some cancers were caused by infections. This suggested the possibility of applying infection-control strategies to cancer control. Vaccines represent the most practical cost-effective technology to prevent wide human suffering and death from many acute infectious diseases, such as small pox or polio. Hitherto applied to control of acute fatal infections, vaccines, if developed, might provide a potent way to control cancer. The articles in the HPV thematic series show success in developing and applying a vaccine against human papilloma virus (HPV). A vaccine is also available against hepatitis B virus (HBV), which causes liver cancer. These vaccines augment the tools available to control the associated cancers. Scientific endeavor continues for six other cancer-associated infections, mostly viruses. Not surprisingly, debate about the safety of vaccines targeting cancer has been triggered in the scientific community. Questions about safety have been raised for those populations where other means to control these cancers may be available. Although it is difficult to quantify risk from vaccines in individuals where other cancer control services exist, it is likely to be low. Vaccines are much safer today than before. Technological advancement in vaccine development and manufacture and improved regulatory review and efficient distribution have minimized substantially the risk for harm from vaccines. Formal and informal debate about the pros and cons of applying vaccines as a cancer control tools is ongoing in scientific journals and on the web. Infectious Agents and Cancer

  7. Therapeutic vaccines and cancer: focus on DPX-0907

    Directory of Open Access Journals (Sweden)

    Karkada M

    2014-02-01

    Full Text Available Mohan Karkada,1,2 Neil L Berinstein,3 Marc Mansour1 1ImmunoVaccine Inc, 2Department of Microbiology/Immunology, Dalhousie University, Halifax, NS, Canada; 3Ontario Institute for Cancer Research, Toronto, ON, Canada Abstract: In an attempt to significantly enhance immunogenicity of peptide cancer vaccines, we developed a novel non-emulsion depot-forming vaccine platform called DepoVax™ (DPX. Human leukocyte antigen (HLA-A2 restricted peptides naturally presented by cancer cells were used as antigens to create a therapeutic cancer vaccine, DPX-0907. In a phase I clinical study, the safety and immune-activating potential of DPX-0907 in advanced-stage breast, ovarian, and prostate cancer patients were examined, following encouraging results in HLA-A2 transgenic mice. The DPX-0907 vaccine was shown to be safe and well tolerated, with injection-site reactions being the most commonly reported adverse event. Vaccinated cancer patients exhibited a 61% immune response rate, with higher response rates in the breast and ovarian cancer patient cohorts. In keeping with the higher immune efficacy of this vaccine platform, antigen-specific responses were detected in 73% of immune responders after just one vaccination. In 83% of responders, peptide-specific T-cells were detected at two or more time points post-vaccination, with 64% of these 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. The novel DPX formulation promotes multifunctional effector/memory responses to peptide-based tumor-associated antigens. The data support the capacity of DPX-0907 to elicit type-1 biased immune responses, warranting further clinical development of the vaccine. In this review, we discuss the rationale for developing DPX-based therapeutic cancer vaccine(s, with a focus on DPX-0907, aimed at inducing efficient anti-tumor immunity that may

  8. Are Fewer Cervical Cancer Screenings Needed After HPV Vaccine?

    Science.gov (United States)

    ... html Are Fewer Cervical Cancer Screenings Needed After HPV Vaccine? Less testing could reduce risk of false positives ... said. Women vaccinated with earlier versions of the HPV vaccine -- which protect against the two worst cancer-causing ...

  9. TB vaccines in clinical development

    OpenAIRE

    McShane, H; Ginsberg, AM; Ruhwald, M.; Mearns, H

    2016-01-01

    The 4th Global Forum on TB Vaccines, convened in Shanghai, China, from 21 – 24 April 2015, brought together a wide and diverse community involved in tuberculosis vaccine research and development to discuss the current status of, and future directions for this critical effort. This paper summarizes the sessions on TB Vaccines in Clinical Development, and Clinical Research: Data and Findings. Summaries of all sessions from the 4th Global Forum are compiled in a special supplement of Tuberculosi...

  10. Human papillomavirus vaccination guideline update: American Cancer Society guideline endorsement.

    Science.gov (United States)

    Saslow, Debbie; Andrews, Kimberly S; Manassaram-Baptiste, Deana; Loomer, Lacey; Lam, Kristina E; Fisher-Borne, Marcie; Smith, Robert A; Fontham, Elizabeth T H

    2016-09-01

    Answer questions and earn CME/CNE The American Cancer Society (ACS) reviewed and updated its guideline on human papillomavirus (HPV) vaccination based on a methodologic and content review of the Advisory Committee on Immunization Practices (ACIP) HPV vaccination recommendations. A literature review was performed to supplement the evidence considered by the ACIP and to address new vaccine formulations and recommendations as well as new data on population outcomes since publication of the 2007 ACS guideline. The ACS Guideline Development Group determined that the evidence supports ACS endorsement of the ACIP recommendations, with one qualifying statement related to late vaccination. The ACS recommends vaccination of all children at ages 11 and 12 years to protect against HPV infections that lead to several cancers and precancers. Late vaccination for those not vaccinated at the recommended ages should be completed as soon as possible, and individuals should be informed that vaccination may not be effective at older ages. CA Cancer J Clin 2016;66:375-385. © 2016 American Cancer Society.

  11. Cancer vaccines at an inflexion point: what next?

    Directory of Open Access Journals (Sweden)

    Obrocea Mihail

    2011-09-01

    Full Text Available Abstract With the approval of the first therapeutic cancer vaccines for veterinarian and human use, the field reached a significant milestone after a considerable interval of tumultuous research and development marked by numerous ups and downs. As the mechanism of action and clinical benefit afforded by this class of agents are starkly different from that of conventional or small targeted therapies for cancer, there are still numerous hurdles that need to be overcome to fully unleash their potential. These challenges and efforts are illustrated in a book just published on this subject, a non-exhaustive yet representative synopsis of the latest advances in cancer vaccine technologies in various stages of development. Major lessons resulting from clinical testing of cancer vaccines and other immune interventions, are being integrated in novel, cutting edge platform technologies that blur the distinction between passive and active immunotherapies as well as carry the promise of fundamentally changing and improving the management of patients with cancer.

  12. Cancer vaccines at an inflexion point: what next?

    Science.gov (United States)

    Bot, Adrian; Obrocea, Mihail; Marincola, Francesco M

    2011-09-09

    With the approval of the first therapeutic cancer vaccines for veterinarian and human use, the field reached a significant milestone after a considerable interval of tumultuous research and development marked by numerous ups and downs. As the mechanism of action and clinical benefit afforded by this class of agents are starkly different from that of conventional or small targeted therapies for cancer, there are still numerous hurdles that need to be overcome to fully unleash their potential. These challenges and efforts are illustrated in a book just published on this subject, a non-exhaustive yet representative synopsis of the latest advances in cancer vaccine technologies in various stages of development. Major lessons resulting from clinical testing of cancer vaccines and other immune interventions, are being integrated in novel, cutting edge platform technologies that blur the distinction between passive and active immunotherapies as well as carry the promise of fundamentally changing and improving the management of patients with cancer.

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

    Directory of Open Access Journals (Sweden)

    Samantha Sayers

    2012-01-01

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

  14. Pancreatic cancer vaccine: a unique potential therapy

    Directory of Open Access Journals (Sweden)

    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

  15. Evaluation of Prostatic Acid Phosphatase (PAP) as a Candidate Antigen for the Development of Cancer Vaccines for Prostate Cancer

    Science.gov (United States)

    2001-10-01

    colony-stimulating factor as a vaccine adjuvant elicits both a cellular and humoral response to recombinant human granu - locyte-macrophage colony...cells in recruiting CD8+ CTLs (4) and other inflammatory cells such as macrophages and eosinophils (5). CTLs have generally been believed to be the... eosinophils . Cytotoxic T lymphocytes (CTL) have long been considered to be the primary effector cell population critical for effective antitumor immunity

  16. Prostate cancer vaccines in clinical trials.

    Science.gov (United States)

    Lubaroff, David M

    2012-07-01

    This review presents important information about the current state of the art for vaccine immunotherapy of prostate cancer. It includes important preclinical research for each of the important prostate cancer vaccines to have reached clinical trials. To date, the only prostate cancer vaccine that has completed Phase III trials and has been approved and licensed by the US FDA is Sipuleucel-T, which immunizes patients against the prostate-associated antigen prostatic acid phosphatase. The benefits and concerns associated with the vaccine are presented. A current Phase III trial is currently underway using the vaccinia-based prostate-specific antigen vaccine Prostvac-TRICOM. Other immunotherapeutic vaccines in trials include the Ad/prostate-specific antigen vaccine Ad5-prostate-specific antigen and the DNA/prostatic acid phosphatase vaccine. A cellular vaccine, GVAX, has been in clinical trials but has not seen continuous study. This review also delves into the multiple immune regulatory elements that must be overcome in order to obtain strong antitumor-associated antigen immune responses capable of effectively destroying prostate tumor cells.

  17. Cancer treatment: the combination of vaccination with other therapies

    DEFF Research Database (Denmark)

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

    2008-01-01

    their escape from cytotoxic therapies represent prime vaccination candidates. The characterization of a high number of tumor antigens allow the concurrent or serial immunological targeting of different proteins associated with such cancer traits. Moreover, while vaccination in itself is a promising new......Harnessing of the immune system by the development of 'therapeutic' vaccines, for the battle against cancer has been the focus of tremendous research efforts over the past two decades. As an illustration of the impressive amounts of data gathered over the past years, numerous antigens expressed...... on the surface of cancer cells, have been characterized. To this end, recent years research has focussed on characterization of antigens that play an important role for the growth and survival of cancer cells. Anti-apoptotic molecules like survivin that enhance the survival of cancer cells and facilitate...

  18. IL-13 receptor-directed cancer vaccines and immunotherapy.

    Science.gov (United States)

    Nakashima, Hideyuki; Husain, Syed R; Puri, Raj K

    2012-04-01

    Many immunotherapy approaches including therapeutic cancer vaccines targeting specific tumor-associated antigens are at various stages of development. Although the significance of overexpression of (IL-13Rα2) in cancer is being actively investigated, we have reported that IL-13Rα2 is a novel tumor-associated antigen. The IL-13Rα2-directed cancer vaccine is one of the most promising approaches to tumor immunotherapy, because of the selective expression of IL-13Rα2 in various solid tumor types but not in normal tissues. In this article, we will summarize its present status and potential strategies to improve IL-13Rα2-directed cancer vaccines for an optimal therapy of cancer.

  19. Human Papilloma Virus Vaccine: Future of Cervical Cancer Prevention

    Directory of Open Access Journals (Sweden)

    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.

  20. Carbohydrate-based cancer vaccines: target cancer with sugar bullets.

    Science.gov (United States)

    Liu, Chang-Cheng; Ye, Xin-Shan

    2012-08-01

    With the booming development of glycobiology and glycochemistry, more and more structures of tumor-associated carbohydrate antigens (TACAs) are identified. Their broad expression and high specificity in cancer make them important targets to develop cancer vaccines or immunotherapies. However, most of the TACAs are T cell-independent antigens, they cannot elicit a powerful enough immune response to prevent or treat cancer. Immunotolerance and immunosuppression are more easily induced due to their endogenous properties and the declining immunity of the patients. This review summarizes the recent efforts to overcome these obstacles: coupling the carbohydrate antigens to proper carriers such as proteins or some small molecule carriers, and chemically modifying the structures of the TACAs to enhance the immunogenicity of TACAs and break the immunotolerance.

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

    Directory of Open Access Journals (Sweden)

    Mavrutenkov V.V.

    2016-09-01

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

  2. Current trends in cancer vaccines--a bioinformatics perspective.

    Science.gov (United States)

    Sankar, Shanju; Nayanar, Sangeetha K; Balasubramanian, Satheesan

    2013-01-01

    Cancer vaccine development is in the process of becoming reality in future, due to successful phase II/III clinical trials. However, there are still problems due to the specificity of tumor antigens and weakness of tumor associated antigens in eliciting an effective immune response. Computational models to assess the vaccine efficacy have helped to improve and understand what is necessary for personalized treatment. Further research is needed to elucidate the mechanisms of activation of antigen specific cytotoxic T lymphocytes, decreased TREG number functionality and antigen cascade, so that overall improvement in vaccine efficacy and disease free survival can be attained. T cell epitomic based in sillico approaches might be very effective for the design and development of novel cancer vaccines.

  3. DNA vaccines, electroporation and their applications in cancer treatment.

    Science.gov (United States)

    Lee, Si-Hyeong; Danishmalik, Sayyed Nilofar; Sin, Jeong-Im

    2015-01-01

    Numerous animal studies and recent clinical studies have shown that electroporation-delivered DNA vaccines can elicit robust Ag-specific CTL responses and reduce disease severity. However, cancer antigens are generally poorly immunogenic, requiring special conditions for immune response induction. To date, many different approaches have been used to elicit Ag-specific CTL and anti-neoplastic responses to DNA vaccines against cancer. In vivo electroporation is one example, whereas others include DNA manipulation, xenogeneic antigen use, immune stimulatory molecule and immune response regulator application, DNA prime-boost immunization strategy use and different DNA delivery methods. These strategies likely increase the immunogenicity of cancer DNA vaccines, thereby contributing to cancer eradication. However, cancer cells are heterogeneous and might become CTL-resistant. Thus, understanding the CTL resistance mechanism(s) employed by cancer cells is critical to develop counter-measures for this immune escape. In this review, the use of electroporation as a DNA delivery method, the strategies used to enhance the immune responses, the cancer antigens that have been tested, and the escape mechanism(s) used by tumor cells are discussed, with a focus on the progress of clinical trials using cancer DNA vaccines.

  4. Rhodococcus equi (Prescottella equi) vaccines; the future of vaccine development.

    Science.gov (United States)

    Giles, C; Vanniasinkam, T; Ndi, S; Barton, M D

    2015-09-01

    For decades researchers have been targeting prevention of Rhodococcus equi (Rhodococcus hoagui/Prescottella equi) by vaccination and the horse breeding industry has supported the ongoing efforts by researchers to develop a safe and cost effective vaccine to prevent disease in foals. Traditional vaccines including live, killed and attenuated (physical and chemical) vaccines have proved to be ineffective and more modern molecular-based vaccines including the DNA plasmid, genetically attenuated and subunit vaccines have provided inadequate protection of foals. Newer, bacterial vector vaccines have recently shown promise for R. equi in the mouse model. This article describes the findings of key research in R. equi vaccine development and looks at alternative methods that may potentially be utilised.

  5. 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.

  6. Screening, HPV Vaccine Can Prevent Cervical Cancer: FDA

    Science.gov (United States)

    ... https://medlineplus.gov/news/fullstory_163464.html Screening, HPV Vaccine Can Prevent Cervical Cancer: FDA Agency recommends ... cancer, which is caused by the human papillomavirus (HPV). An FDA-approved vaccine called Gardasil 9 protects ...

  7. Chinese vaccine products go global: vaccine development and quality control.

    Science.gov (United States)

    Xu, Miao; Liang, Zhenglun; Xu, Yinghua; Wang, Junzhi

    2015-05-01

    Through the continuous efforts of several generations, China has become one of the few countries in the world that is capable of independently addressing all the requirements by the Expanded Program on Immunization. Regulatory science is applied to continuously improve the vaccine regulatory system. Passing the prequalification by WHO has allowed Chinese vaccine products to go global. Chinese vaccine products not only secure disease prevention and control domestically but also serve the needs for international public health. This article describes the history of Chinese vaccine development, the current situation of Chinese vaccine industry and its contribution to the prevention and control of infectious diseases. We also share our experience of national quality control and vaccine regulation during the past decades. China's experience in vaccine development and quality control can benefit other countries and regions worldwide, including the developing countries.

  8. Get Vaccinated! and Get Tested! Developing Primary and Secondary Cervical Cancer Prevention Videos for a Haitian Kreyòl-Speaking Audience.

    Science.gov (United States)

    Frett, Brigitte; Aquino, Myra; Fatil, Marie; Seay, Julia; Trevil, Dinah; Fièvre, Michèle Jessica; Kobetz, Erin

    2016-05-01

    Although routine screening reduces cervical cancer rates between 60% and 90%, thousands of women worldwide are diagnosed with the disease on an annual basis because of inadequate screening. Haitian women in South Florida experience a disproportionate burden of cervical cancer, with disease rates 4 times higher than the average for women in Miami. An ongoing community-based participatory research initiative to assess and reduce this burden has revealed that a complex interplay of factors contributes to a lack of access to screening in this community, including socioeconomics, language barriers, and traditional understandings of health and disease. In an effort to address some of these barriers and encourage uptake of primary and secondary cervical cancer prevention strategies, 2 videos on cervical cancer prevention were created using a community-based participatory research framework. The video screenplays were created by a Haitian screenwriter using evidence-based medical information provided by academic researchers. The films feature Haitian actors speaking a Haitian Kreyòl dialogue with a storyline portraying friends and family discussing human papillomavirus disease and vaccination, Papanicolaou testing, and cervical cancer. Focus groups held with Haitian women in South Florida suggested that the films are engaging; feature relatable characters; and impact knowledge about human papillomavirus, cervical cancer development, and current prevention recommendations.

  9. Cancer vaccines: harnessing the potential of anti-tumor immunity.

    Science.gov (United States)

    Suckow, Mark A

    2013-10-01

    Although the presence of cancer suggests failure of the immune system to protect against development of tumors, the possibility that immunity can be redirected and focused to generate an anti-tumor response offers great translational possibility. The key to this is identifying antigens likely to be present in any given tumor and functionally critical to tumor survival and growth. Such tumor-associated antigens (TAAs) are varied and optimally should be absent from normal tissue. Of particular interest are TAAs associated with the tumor stroma, as immunity directed against the stroma may restrict the ability of the tumor to grow and metastasize. Important to directing the immune system toward an effect anti-tumor response is the understanding of how TAAs are processed and how the tumor is able to evade immune elimination. The process of immunoediting happens in response to the selective pressure that the immune system places upon tumor cell populations and allows for emergence of tumor cells capable of escaping immune destruction. Efforts to harness the immune system for clinical application has been aided by vaccines based on purified recombinant protein or nucleic acid TAAs. For example, a vaccine for canine melanoma has been developed and approved based on immunization with DNA components of tyrosinase, a glycoprotein essential to melanin synthesis. The performance of cancer vaccines has been aided in some cases when supplemented with immunostimulatory molecules such as interleukin 2 or a novel extracellular matrix vaccine adjuvant. Vaccines with the broadest menu of antigenic targets may be those most likely to succeed against cancer. For this reason, tissue vaccines produced from harvested tumor material may offer significant benefit. With several cancer vaccines on the veterinary and human markets, efforts to understand basic tumor immunology are soon to yield great dividends.

  10. Communicating vaccine safety during the development and introduction of vaccines.

    Science.gov (United States)

    Kochhar, Sonali

    2015-01-01

    Vaccines are the best defense available against infectious diseases. Vaccine safety is of major focus for regulatory bodies, vaccine manufacturers, public health authorities, health care providers and the public as vaccines are often given to healthy children and adults as well as to pregnant woman. Safety assessment is critical at all stages of vaccine development. Effective, clear and consistent communication of the risks and benefits of vaccines and advocacy during all stages of clinical research (including the preparation, approvals, conduct of clinical trials through the post marketing phase) is critically important. This needs to be done for all major stakeholders (e.g. community members, Study Team, Health Care Providers, Ministry of Health, Regulators, Ethics Committee members, Public Health Authorities and Policy Makers). Improved stakeholder alignment would help to address some of the concerns that may affect the clinical research, licensing of vaccines and their wide-spread use in immunization programs around the world.

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

    Science.gov (United States)

    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

  12. Cancer vaccines at an inflexion point: what next?

    OpenAIRE

    Obrocea Mihail; Marincola Francesco M; Bot Adrian

    2011-01-01

    Abstract With the approval of the first therapeutic cancer vaccines for veterinarian and human use, the field reached a significant milestone after a considerable interval of tumultuous research and development marked by numerous ups and downs. As the mechanism of action and clinical benefit afforded by this class of agents are starkly different from that of conventional or small targeted therapies for cancer, there are still numerous hurdles that need to be overcome to fully unleash their po...

  13. 人乳头瘤病毒疫苗预防宫颈癌的应用%Application of HPV Vaccines in Preventing Development of the Cervical Cancer

    Institute of Scientific and Technical Information of China (English)

    夏巧凡; 何莲芝

    2015-01-01

    Cervical cancer causes serious damage to women′s health. It is clear that human papillomavirus (HPV) infection is the major pathogenic factor. HPV invades the organism by subtle injures. When E6 or E7 oncoprotein is continous expression in the epithelial tissue, high-risk HPV infections contribute to tumorigenicity. Detection of high-risk HPV infection and virus oncoprotein still cannot prevent cervical cancer effectively. Researchers begin to develop a vaccine against the HPV virus, and to prevent HPV infections from the sources, hoping to achieve the primary prevention of cervical cancer. Currently bivalent vaccine Cervarix against HPV 16/18 and quadrivalent vaccine Gardasil against HPV 16/18/11/16 have been approved for marketing. Prophylactic HPV vaccines have been used widely on a global scale and obtained significant effect. A new generation of prophylactic HPV vaccines have made a breakthrough in solving problems including cost, persistence and broad-spectrum immune. Cervical cancer is expected to become the first preventable cancer in the history of human anti-tumor. This review concentrates on the biological characteristics and pathogenic mechanism of HPV and the current application and situation of prophylactic HPV vaccines.%宫颈癌严重危害女性健康,现已明确人乳头瘤病毒(HPV)感染是其主要致病因素。HPV通过机体的细微损伤入侵,HPV E6和E7癌蛋白中的1种或2种持续表达是高危型HPV感染致瘤的关键所在,检测高危型HPV感染及病毒癌蛋白仍不能有效预防宫颈癌。研究者们正着手研制针对HPV的病毒疫苗,从源头预防HPV感染,以期实现宫颈癌的一级预防。目前已有针对HPV16/18型的二价疫苗Cervarix和针对HPV16/18/11/6型的四价疫苗Gardasil的认证上市,预防性HPV疫苗已在全球范围内推广使用并取得显著效果。新一代预防性HPV疫苗在解决疫苗的成本、持久性和广谱免疫问题上取得突破性进展,

  14. Recent update in HIV vaccine development

    OpenAIRE

    Shin, So Youn

    2016-01-01

    Despite the tremendous efforts to develop a successful human immunodeficiency virus (HIV) vaccine, the quest for a safe and effective HIV vaccine seems to be remarkably long and winding. Disappointing results from previous clinical trials of VaxGen's AIDSVAXgp120 vaccine and MRKAd5 HIV-1 Gag/Pol/Nef vaccine emphasize that understanding the correlates of immune protection in HIV infection is the key to solve the puzzle. The modest vaccine efficacy from RV144 trial and the successive results ob...

  15. Current vaccination strategies for prostate cancer.

    NARCIS (Netherlands)

    Joniau, S.; Abrahamsson, P.A.; Bellmunt, J.; Figdor, C.G.; Hamdy, F.; Verhagen, P.; Vogelzang, N.J.; Wirth, M.; Poppel, H. van; Osanto, S.

    2012-01-01

    CONTEXT: The first therapeutic cancer vaccine demonstrating effectiveness in a phase 3 study was approved by the US Food and Drug Administration on 29 April 2010. The pivotal trial demonstrated overall survival (OS) benefit in patients treated with antigen-loaded leukapheresis cells compared with a

  16. 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...... endpoints, including toxicity and response evaluation. This paper aims to review the technical aspects and clinical impact of vaccination trials, focusing on the generation of DC-based vaccines, evaluation of immunologic parameters and design of clinical trials necessary to meet the need for good laboratory...

  17. Influenza vaccination in children being treated with chemotherapy for cancer

    NARCIS (Netherlands)

    G.M. Goossen; L.C.M. Kremer; M.D. van de Wetering

    2009-01-01

    Background Influenza infection is a potential cause of severe morbidity in children with cancer, therefore vaccination against influenza is recommended. However, there are conflicting data concerning the immune response to influenza vaccination in children with cancer and the value of vaccination re

  18. Identification of novel helper epitope peptides of Survivin cancer-associated antigen applicable to developing helper/killer-hybrid epitope long peptide cancer vaccine.

    Science.gov (United States)

    Ohtake, Junya; Ohkuri, Takayuki; Togashi, Yuji; Kitamura, Hidemitsu; Okuno, Kiyotaka; Nishimura, Takashi

    2014-09-01

    We identified novel helper epitope peptides of Survivin cancer antigen, which are presented to both HLA-DRB1*01:01 and DQB1*06:01. The helper epitope also contained three distinct Survivin-killer epitopes presented to HLA-A*02:01 and A*24:02. This 19 amino-acids epitope peptide (SU18) induced weak responses of Survivin-specific CD4(+) and CD8(+) T cells though it contained both helper and killer epitopes. To enhance the vaccine efficacy, we synthesized a long peptide by conjugating SU18 peptide and another DR53-restricted helper epitope peptide (SU22; 12 amino-acids) using glycine-linker. We designated this artificial 40 amino-acids long peptide containing two helper and three killer epitopes as Survivin-helper/killer-hybrid epitope long peptide (Survivin-H/K-HELP). Survivin-H/K-HELP allowed superior activation of IFN-γ-producing CD4(+) Th1 cells and CD8(+) Tc1 cells compared with the mixture of its component peptides (SU18 and SU22) in the presence of OK-432-treated monocyte-derived DC (Mo-DC). Survivin-H/K-HELP-pulsed Mo-DC pretreated with OK-432 also exhibited sustained antigen-presentation capability of stimulating Survivin-specific Th1 cells compared with Mo-DC pulsed with a mixture of SU18 and SU22 short peptides. Moreover, we demonstrated that Survivin-H/K-HELP induced a complete response in a breast cancer patient with the induction of cellular and humoral immune responses. Thus, we believe that an artificially synthesized Survivin-H/K-HELP will become an innovative cancer vaccine.

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

    Science.gov (United States)

    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.

  20. Vaccine Immunotherapy for Prostate Cancer

    Science.gov (United States)

    2010-05-01

    Unrelated Increased urinary urgency 2 Unrelated Decreased libido 1 Unrelated Increased erectile dysfunct. 2 Unrelated Hot flashes 1 Unrelated...Arm B – Androgen Deprivation Patients Patient Event Grade Vaccine Related APIIAADT-04 Difficulty sleeping 1 Unlikely Increased urinary freq. 2

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

    Directory of Open Access Journals (Sweden)

    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.

  2. Cancer Genome Sequencing and Its Implications for Personalized Cancer Vaccines

    Directory of Open Access Journals (Sweden)

    William E. Gillanders

    2011-11-01

    Full Text Available New DNA sequencing platforms have revolutionized human genome sequencing. The dramatic advances in genome sequencing technologies predict that the $1,000 genome will become a reality within the next few years. Applied to cancer, the availability of cancer genome sequences permits real-time decision-making with the potential to affect diagnosis, prognosis, and treatment, and has opened the door towards personalized medicine. A promising strategy is the identification of mutated tumor antigens, and the design of personalized cancer vaccines. Supporting this notion are preliminary analyses of the epitope landscape in breast cancer suggesting that individual tumors express significant numbers of novel antigens to the immune system that can be specifically targeted through cancer vaccines.

  3. Cancer Genome Sequencing and Its Implications for Personalized Cancer Vaccines

    Energy Technology Data Exchange (ETDEWEB)

    Li, Lijin [Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110 (United States); Goedegebuure, Peter [Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110 (United States); The Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine, St. Louis, MO 63110 (United States); Mardis, Elaine R. [The Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine, St. Louis, MO 63110 (United States); The Genome Institute at Washington University School of Medicine, St. Louis, MO 63108 (United States); Ellis, Matthew J.C. [The Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine, St. Louis, MO 63110 (United States); Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110 (United States); Zhang, Xiuli; Herndon, John M. [Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110 (United States); Fleming, Timothy P. [Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110 (United States); The Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine, St. Louis, MO 63110 (United States); Carreno, Beatriz M. [The Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine, St. Louis, MO 63110 (United States); Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110 (United States); Hansen, Ted H. [The Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine, St. Louis, MO 63110 (United States); Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110 (United States); Gillanders, William E., E-mail: gillandersw@wudosis.wustl.edu [Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110 (United States); The Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine, St. Louis, MO 63110 (United States)

    2011-11-25

    New DNA sequencing platforms have revolutionized human genome sequencing. The dramatic advances in genome sequencing technologies predict that the $1,000 genome will become a reality within the next few years. Applied to cancer, the availability of cancer genome sequences permits real-time decision-making with the potential to affect diagnosis, prognosis, and treatment, and has opened the door towards personalized medicine. A promising strategy is the identification of mutated tumor antigens, and the design of personalized cancer vaccines. Supporting this notion are preliminary analyses of the epitope landscape in breast cancer suggesting that individual tumors express significant numbers of novel antigens to the immune system that can be specifically targeted through cancer vaccines.

  4. Use of Prior Vaccinations for the Development of New Vaccines

    Science.gov (United States)

    Etlinger, H. M.; Gillessen, D.; Lahm, H.-W.; Matile, H.; Schonfeld, H.-J.; Trzeciak, A.

    1990-07-01

    There is currently a need for vaccine development to improve the immunogenicity of protective epitopes, which themselves are often poorly immunogenic. Although the immunogenicity of these epitopes can be enhanced by linking them to highly immunogenic carriers, such carriers derived from current vaccines have not proven to be generally effective. One reason may be related to epitope-specific suppression, in which prior vaccination with a protein can inhibit the antibody response to new epitopes linked to the protein. To circumvent such inhibition, a peptide from tetanus toxoid was identified that, when linked to a B cell epitope and injected into tetanus toxoid-primed recipients, retained sequences for carrier but not suppressor function. The antibody response to the B cell epitope was enhanced. This may be a general method for taking advantage of previous vaccinations in the development of new vaccines.

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

    Science.gov (United States)

    Tsai, Horng-Jyh

    2015-04-01

    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.

  6. HPV vaccine

    Science.gov (United States)

    Vaccine - HPV; Immunization - HPV; Gardasil; HPV2; HPV4; Vaccine to prevent cervical cancer; Genital warts - HPV vaccine; Cervical dysplasia - HPV vaccine; Cervical cancer - HPV vaccine; Cancer of the cervix - HPV vaccine; Abnormal ...

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

    Science.gov (United States)

    Birkett, Ashley J

    2016-06-03

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

  8. Listeria Vaccines for Pancreatic Cancer

    Science.gov (United States)

    2013-10-01

    Immunol 20, 77 (Jan, 2013). 13. S. K. Biswas, C. E. Lewis, J Leukoc Biol 88, 877 (Nov, 2010). 14. L. J. Bayne et al., Cancer Cell 21, 822 (Jun 12, 2012...EMT and dissemination precede prancreatic tumor formation. Cell. 2012; 148:349. 14. Bayne , L.J., Beatty, G.L., Jhala, N., Clark, C.E., Rhim, A.D...immunity in pancreatic cancer. Cancer Cell. 2012; 21:822. 15. Vonderheide, RH, Bajor, DL, Bayne , LJ, and G.L. Beatty. CD40 immunotherapy for pancreatic

  9. Novel Immune-Modulating Cellular Vaccine for Prostate Cancer Immunotherapy

    Science.gov (United States)

    2015-10-01

    AWARD NUMBER: W81XWH-13-1-0423 TITLE: Novel Immune-Modulating Cellular Vaccine for Prostate Cancer Immunotherapy PRINCIPAL INVESTIGATOR: Smita...SUBTITLE 5a. CONTRACT NUMBER W81XWH-13-1-0423 Novel Immune-Modulating Cellular Vaccine for Prostate Cancer Immunotherapy 5b. GRANT NUMBER 5c...immune checkpoint blockade, local CTLA-4 modulation, prostate cancer immunotherapy , prostatic acid phosphatase (PAP), RNA-based vaccines 16

  10. Developing Vaccines to Combat Pandemic Influenza

    Directory of Open Access Journals (Sweden)

    Othmar G. Engelhardt

    2010-02-01

    Full Text Available Influenza vaccine manufacturers require antigenically relevant vaccine viruses that have good manufacturing properties and are safe to use. In developing pandemic vaccine viruses, reverse genetics has been employed as a rational approach that can also be used effectively to attenuate the highly virulent H5N1 virus and at the same time place the H5 HA and N1 NA on a background of PR8, a virus that has been used over many decades to provide high yielding vaccine viruses. Reverse genetics has also been used successfully alongside classical reassorting techniques in the development of (swine flu pandemic A(H1N1v vaccine viruses.

  11. Progress and challenges in the vaccine-based treatment of head and neck cancers

    Directory of Open Access Journals (Sweden)

    Venuti Aldo

    2009-05-01

    Full Text Available Abstract Head and neck (HN cancer represents one of the most challenging diseases because the mortality remains high despite advances in early diagnosis and treatment. Although vaccine-based approaches for the treatment of advanced squamous cell carcinoma of the head and neck have achieved limited clinical success, advances in cancer immunology provide a strong foundation and powerful new tools to guide current attempts to develop effective cancer vaccines. This article reviews what has to be rather what has been done in the field for the development of future vaccines in HN tumours.

  12. Conjugate Meningococcal Vaccines Development: GSK Biologicals Experience

    Directory of Open Access Journals (Sweden)

    Jacqueline M. Miller

    2011-01-01

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

  13. Developing a Successful HIV Vaccine.

    Science.gov (United States)

    Gallo, Robert C

    2015-07-15

    Human immunodeficiency virus (HIV) genome integration indicates that persistent sterilizing immunity will be needed for a successful vaccine candidate. This suggests a need for broad antibodies targeting the Env protein. Immunogens targeting gp120 have been developed that block infection in monkeys and mimic the modest success of the RV144 clinical trial in that protection is short-lived following a decline in antibody-depending cell-mediated cytotoxicity-like antibodies. Attempts to induce antibody persistence have been complicated by a loss of efficacy, presumably by increasing the number of HIV-target cells. The key seems to be achieving an immune balance.

  14. Status of vaccine research and development of vaccines for tuberculosis.

    Science.gov (United States)

    Evans, Thomas G; Schrager, Lew; Thole, Jelle

    2016-06-03

    TB is now the single pathogen that causes the greatest mortality in the world, at over 1.6 million deaths each year. The widely used the 90 year old BCG vaccine appears to have minimal impact on the worldwide incidence despite some efficacy in infants. Novel vaccine development has accelerated in the past 15 years, with 15 candidates entering human trials; two vaccines are now in large-scale efficacy studies. Modeling by three groups has consistently shown that mass vaccination that includes activity in the latently infected population, especially adolescents and young adults, will likely have the largest impact on new disease transmission. At present the field requires better validated animal models, better understanding of a correlate of immunity, new cost-effective approaches to Proof of Concept trials, and increased appreciation by the public health and scientific community for the size of the problem and the need for a vaccine. Such a vaccine is likely to also play a role in the era of increasing antibiotic resistance. Ongoing efforts and studies are working to implement these needs over the next 5 years, which will lead to an understanding that will increase the likelihood of a successful TB vaccine.

  15. Rotavirus vaccines: targeting the developing world.

    Science.gov (United States)

    Glass, Roger I; Bresee, Joseph S; Turcios, Reina; Fischer, Thea K; Parashar, Umesh D; Steele, A Duncan

    2005-09-01

    For the past 2 decades, rotavirus infection, the most common cause of severe diarrhea in children, has been a priority target for vaccine development. This decision to develop rotavirus vaccines is predicated on the great burden associated with fatal rotavirus disease (i.e., 440,000 deaths/year), the firm scientific basis for developing live oral vaccines, the belief that increased investment in development at this time could speed the introduction of vaccines in developing countries, and the appreciation that implementation of a vaccine program should result in a measurable decrease in the number of hospitalizations and deaths associated with rotavirus disease within 2-3 years. RotaShield (Wyeth-Ayerst), the first rotavirus vaccine licensed in the United States, was withdrawn after 9 months because of a rare association of the vaccine with the development of intussusception. In the developing world, this vaccine could still have had a measurable effect, because the benefits of preventing deaths due to rotavirus disease would have been substantially greater than the rare risk of intussusception. Two live oral vaccines being prepared by GlaxoSmithKline and Merck have completed large-scale clinical trials. The GlaxoSmithKline vaccine has been licensed in Mexico and the Dominican Republic, and the Merck vaccine could be licensed in the United States within 1 year; several other candidate vaccines are in earlier stages of testing. However, many challenges remain before any of these vaccines can be incorporated into childhood immunization programs in the developing world. First, vaccine efficacy, which has already been demonstrated in children in industrialized and middle-income countries, needs to be proven in poor developing countries in Africa and Asia. The safety of vaccines with regard to the associated risk of intussusception must be demonstrated as well. Novel financing strategies will be needed to ensure that new vaccines are affordable and available in the

  16. Current status of toxoplasmosis vaccine development.

    Science.gov (United States)

    Kur, Józef; Holec-Gasior, Lucyna; Hiszczyńska-Sawicka, Elzbieta

    2009-06-01

    Toxoplasmosis, caused by an intracellular protozoan parasite, Toxoplasma gondii, is widespread throughout the world. The disease is of major medical and veterinary importance, being a cause of congenital disease and abortion in humans and domestic animals. In addition, recently it has gained importance owing to toxoplasma encephalitis in AIDS patients. In the last few years, there has been considerable progress towards the development of a vaccine for toxoplasmosis, and a vaccine based on the live-attenuated S48 strain was developed for veterinary uses. However, this vaccine is expensive, causes side effects and has a short shelf life. Furthermore, this vaccine may revert to a pathogenic strain and, therefore, is not suitable for human use. Various experimental studies have shown that it may be possible to develop a vaccine against human toxoplasmosis. Recent progress in knowledge of the protective immune response generated by T. gondii and the current status of development of a vaccine for toxoplasmosis are highlighted.

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

    Directory of Open Access Journals (Sweden)

    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.

  18. 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...

  19. Cancer-germline antigen vaccines and epigenetic enhancers

    DEFF Research Database (Denmark)

    Gjerstorff, Morten Frier; Burns, Jorge; Ditzel, Henrik Jorn

    2010-01-01

    can be achieved using epigenetic modifiers. AREAS COVERED IN THIS REVIEW: We provide an overview of the potential of CG antigens as targets for cancer immunotherapy, including advantages and disadvantages. We also discuss the current state of development of CG antigen vaccines, and the potential...... synergistic effect of combining CG antigen immunotherapeutic strategies with epigenetic modifiers. WHAT THE READER WILL GAIN: The reader will gain an overview of the past, present and future role of CG antigens in cancer immunotherapy. TAKE HOME MESSAGE: Chemoimmunotherapy using epigenetic drugs and CG...

  20. Dendritic cell targeting vaccine for HPV-associated cancer

    Science.gov (United States)

    Yin, Wenjie; Duluc, Dorothée; Joo, HyeMee; Oh, SangKon

    2017-01-01

    Dendritic cells (DCs) are major antigen presenting cells that can efficiently prime and activate cellular immune responses. Delivering antigens to in vivo DCs has thus been considered as a promising strategy that could allow us to mount T cell-mediated therapeutic immunity against cancers in patients. Successful development of such types of cancer vaccines that can target in vivo DCs, however, requires a series of outstanding questions that need to be addressed. These include the proper selection of which DC surface receptors, specific DC subsets and DC activators that can further enhance the efficacy of vaccines by promoting effector T cell infiltration and retention in tumors and their actions against tumors. Supplementing these areas of research with additional strategies that can counteract tumor immune evasion mechanisms is also expected to enhance the efficacy of such therapeutic vaccines against cancers. After more than a decade of study, we have concluded that antigen targeting to DCs via CD40 to evoke cellular responses is more efficient than targeting antigens to the same types of DCs via eleven other DC surface receptors tested. In recent work, we have further demonstrated that a prototype vaccine (anti-CD40-HPV16.E6/7, a recombinant fusion protein of anti-human CD40 and HPV16.E6/7 protein) for HPV16-associated cancers can efficiently activate HPV16.E6/7-specific T cells, particularly CD8+ T cells, from the blood of HPV16+ head-and-neck cancer patients. Moreover, anti-CD40-HPV16.E6/7 plus poly(I:C) can mount potent therapeutic immunity against TC-1 tumor expressing HPV16.E6/7 protein in human CD40 transgenic mice. In this manuscript, we thus highlight our recent findings for the development of novel CD40 targeting immunotherapeutic vaccines for HPV16-associated malignancies. In addition, we further discuss several of key questions that still remain to be addressed for enhancing therapeutic immunity elicited by our prototype vaccine against HPV16

  1. 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.

  2. Interview. Cancer vaccines and immunotherapy of autoimmune diseases.

    Science.gov (United States)

    Apostolopoulos, Vasso

    2009-01-01

    Vasso Apostolopoulos heads the Immunology and Vaccine Laboratory of Burnet Institute (Australia). She completed her PhD in 1995 at the Austin Research Institute (Australia). Her work on cancer vaccine development has been in clinical trial since 1994. In the last 16 years, she has received more than 100 awards/honors for her achievements. Most notable are the Premiers Award for Medical Research, Victorian Young Australian of the Year, Channel 10/Herald Sun Young Achiever of the Year, Victorian Tall Poppy, inductee into the Victorian Honour Roll of Women, a torchbearer in the International Athens 2004 Olympic Torch Relay and was named Woman of the Year. In 1998, she received the prestigious NHMRC CJ Martin Fellowship and undertook research at the Scripps Research Institute (CA, USA) until 2001. In 2001, she returned to the Austin Research Institute (now the Burnet Institute) and was a NHMRC RD Wright Fellow until 2007. She is currently a Professor, Principle Research Fellow, Sir Zelman Cowen Cancer Research Fellow, Australia Day Ambassador and a Patron of the Womens Health Network. She has published more than 120 papers and books and is an inventor on 12 patents. She is on the board and a regular reviewer for a number of journals. Her current interests are in the development of new improved cancer vaccines and new modes of antigen delivery for immune stimulation. She is also interested in the 3D x-ray crystal structures of peptide-MHC complexes.

  3. Development of Mycoplasma hyopneumoniae Recombinant Vaccines.

    Science.gov (United States)

    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.

  4. Vaccines: from empirical development to rational design.

    Directory of Open Access Journals (Sweden)

    Christine Rueckert

    Full Text Available Infectious diseases are responsible for an overwhelming number of deaths worldwide and their clinical management is often hampered by the emergence of multi-drug-resistant strains. Therefore, prevention through vaccination currently represents the best course of action to combat them. However, immune escape and evasion by pathogens often render vaccine development difficult. Furthermore, most currently available vaccines were empirically designed. In this review, we discuss why rational design of vaccines is not only desirable but also necessary. We introduce recent developments towards specifically tailored antigens, adjuvants, and delivery systems, and discuss the methodological gaps and lack of knowledge still hampering true rational vaccine design. Finally, we address the potential and limitations of different strategies and technologies for advancing vaccine development.

  5. Advances and perspectives of colorectal cancer stem cell vaccine.

    Science.gov (United States)

    Guo, Mei; Dou, Jun

    2015-12-01

    Colorectal cancer is essentially an environmental and genetic disease featured by uncontrolled cell growth and the capability to invade other parts of the body by forming metastases, which inconvertibly cause great damage to tissues and organs. It has become one of the leading causes of cancer-related mortality in the developed countries such as United States, and approximately 1.2 million new cases are yearly diagnosed worldwide, with the death rate of more than 600,000 annually and incidence rates are increasing in most developing countries. Apart from the generally accepted theory that pathogenesis of colorectal cancer consists of genetic mutation of a certain target cell and diversifications in tumor microenvironment, the colorectal cancer stem cells (CCSCs) theory makes a different explanation, stating that among millions of colon cancer cells there is a specific and scanty cellular population which possess the capability of self-renewal, differentiation and strong oncogenicity, and is tightly responsible for drug resistance and tumor metastasis. Based on these characteristics, CCSCs are becoming a novel target cells both in the clinical and the basic studies, especially the study of CCSCs vaccines due to induced efficient immune response against CCSCs. This review provides an overview of CCSCs and preparation technics and targeting factors related to CCSCs vaccines in detail.

  6. Issues Related to Recent Dengue Vaccine Development

    OpenAIRE

    Konishi, Eiji

    2011-01-01

    Dengue fever (DF) and dengue hemorrhagic fever (DHF) are mosquito-transmitted diseases of global importance. Despite significant research efforts, no approved vaccines or antiviral drugs against these diseases are currently available. This brief article reviews the status of dengue vaccine development, with particular emphasis on the vaccine strategies in more advanced stages of evaluation; these include traditional attenuation, chimerization and engineered attenuation. Several aspects of the...

  7. Dendritic cell vaccines in cancer immunotherapy: from biology to translational medicine

    Institute of Scientific and Technical Information of China (English)

    Hongmei Xu; Xuetao Cao

    2011-01-01

    According to the GLOBOCAN reports,there were about 12.7 million cancer cases and 7.6 million cancer deaths in 2008,and the cancer burden continues to increase worldwide [1].At present,the common treatments for cancer include surgery,chemotherapy,radiotherapy,and immunotherapy.Immunotherapy aims to enhance or regulate the patient's own immune response to fight against tumors.It represents a novel and effective strategy in cancer treatments,but,generally,its efficacy needs to be improved [2].Cancer vaccination is an important and promising approach in cancer immunotherapy.For many years,prophylactic vaccines have exhibited profound accomplishment in preventing serious infectious diseases in humankind,including polio,small pox,and diphtheria.However,cancer vaccines are vastly different from the prophylactic vaccines in that they are aimed to eliminate preexisting tumors.Furthermore,the immune system is immunosuppressed in most cancer patients,so it is much more difficult to develop effective cancer vaccines.

  8. The Prevention of Liver Cancer by HBV Vaccine Program

    Institute of Scientific and Technical Information of China (English)

    TAO Xiong

    2002-01-01

    Objective To recognize the HBV vaccine program for prevention of the hepatic cancer.Methods To discuss the relation between the HBV and hepatic cancer arising, and to discuss the immunology respond of the HBV vaccine (HBV surface antigen protein) in our patient group. Result Our data indicates that the predisposing of the HBV infection is required for the hepatic cancer arising and for the high expression of the AFP gene, and our data indicates that the HBV vaccine can induce highly immuno respond in about 78.8 % of the adult for achieving the HBV prevention status and the hepatic cancer prevention status.

  9. Development of Novel Vaccines against Enterovirus-71

    Directory of Open Access Journals (Sweden)

    Pinn Tsin Isabel Yee

    2015-12-01

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

  10. Development of Experimental Vaccines Against Liver Flukes.

    Science.gov (United States)

    Yap, Huan Yong; Smooker, Peter M

    2016-01-01

    A multitude of experimental vaccines have been developed against liver flukes in the past. However, there has yet to be the development of a commercial livestock vaccine. Reasons for this may be multiple, and include the lack of identification of the best antigen(s), or the immune response induced by those antigens not being appropriate in either magnitude or polarity (and therefore not protective). Cathepsin proteases are the major component of the excretory/secretory (ES) material of liver flukes in all stages of their life cycle in the definitive host and are the primary antigens of interest for the vaccine development in many studies. Hence, this chapter presents the methodologies of using cathepsin proteases as targeted antigens in recombinant protein and DNA vaccine development to engender protective immune responses against fasciolosis.First, the experimental vaccines developed in the past and the criteria of an effective vaccine for fasciolosis are briefly reviewed. Then flowcharts for recombinant protein vaccine and DNA vaccine development are presented, followed by the detailed materials and methodologies.

  11. Recent progress in dengue vaccine development

    Institute of Scientific and Technical Information of China (English)

    Jianchun; Wei; Hui; Chen; Jing; An

    2014-01-01

    Dengue virus(DENV) has four distinct serotypes. DENV infection can result in classic dengue fever and life-threatening dengue hemorrhagic fever/dengue shock syndrome. In recent decades, DENV infection has become an important public health concern in epidemic-prone areas. Vaccination is the most effective measure to prevent and control viral infections. However, several challenges impede the development of effective DENV vaccines, such as the lack of suitable animal models and the antibody-dependent enhancement phenomenon. Although no licensed DENV vaccine is available, significant progress has been made. This review summarizes candidate DENV vaccines from recent investigations.

  12. DENGUE VACCINE, CHALLENGES, DEVELOPMENT AND STRATEGIES

    Directory of Open Access Journals (Sweden)

    Dewi Marbawati

    2014-08-01

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

  13. Vaccine therapy with sipuleucel-T (Provenge) for prostate cancer.

    Science.gov (United States)

    Thara, Eddie; Dorff, Tanya B; Pinski, Jacek K; Quinn, David I

    2011-08-01

    As the most common malignancy among North American males, prostate cancer causes more than 30,000 deaths each year. After local and hormonal treatments, a great number of patients ultimately progressed to castrate-resistant prostate cancer (CRPC), in which chemotherapy provides a small survival advantage, but with significant toxicities. In the past decade, prostate cancer has become a target for several immunotherapeutic approaches. Sipuleucel-T (Provenge®, or APC8015) is a novel cancer vaccine developed from autologous dendritic cells (DC) loaded with engineered fusion protein of prostatic acid phosphatase (PAP) and granulocyte-macrophage colony-stimulating factor (GM-CSF). Phase I and Phase II trials show that the vaccine is safe and effective in creating immune responses toward the fusion-protein target antigen, PAP-GM-CSF also call PA2024. Recent Phase III studies also demonstrated sipuleucel-T's efficacy in prolonging median survival in patients with CRPC, despite little or no effect on clinical disease progression or surrogates such as serum PSA kinetics. Subsequently, the United States Food and Drug Administration approved sipuleucel-T for the treatment of asymptomatic or minimally symptomatic CRPC in April 2010. Filings are projected with international regulatory agencies in 2011. While the development of sipuleucel-T provides an option for patients with early CRPC, it also introduces physicians and researchers to new unanswered questions regarding its optimal clinical use and questions about mechanism of action and combination and sequencing with other agents.

  14. Society of behavioral medicine supports increasing HPV vaccination uptake: an urgent opportunity for cancer prevention.

    Science.gov (United States)

    Peterson, Caryn E; Dykens, J Andrew; Brewer, Noel T; Buscemi, Joanna; Watson, Karriem; Comer-Hagans, DeLawnia; Ramamonjiarivelo, Zo; Fitzgibbon, Marian

    2016-12-01

    Human papillomavirus (HPV) vaccine coverage remains low in the USA. The Society for Behavioral Medicine (SBM) supports the goals outlined by Healthy People 2020, the President's Cancer Panel, and the National Vaccine Advisory Committee to increase vaccination coverage among both males and females. SBM makes the following recommendations in support of efforts to reduce structural and other barriers to HPV vaccination services in order to increase rates of series completion. We encourage legislators and other policymakers to improve administration authority, insurance coverage, and reimbursement rates to healthcare providers who make the HPV vaccine available to adolescents; provide instrumental support to fund the development of school curricula on HPV vaccination; and increase public awareness that HPV vaccination can prevent cancer. We urge healthcare providers and healthcare systems to increase the strength, quality, and consistency of HPV vaccination recommendations for all eligible patients; to treat HPV vaccination as a routine preventive service; employ culturally appropriate communication strategies in clinical settings to educate eligible patients, parents, and guardians about the importance, effectiveness, and safety of HPV vaccination; and to strengthen and better coordinate the use of electronic medical records and immunization information systems.

  15. Vaccines against biologic agents: uses and developments.

    Science.gov (United States)

    Ales, Noel C; Katial, Rohit K

    2004-03-01

    Although the Geneva protocol that prohibits the use of chemical and biologic weapons was ratified in 1925, many countries failed to accept this protocol: others stipulated retaliation, and some, like the United States, did not ratify the protocol for decades. This delay allowed the continued development of chemical and biologic agents. Members of the health care community are responsible for determining the best way to protect society from the potentially devastating effects of these biologic agents. Ideally,these diseases would be prevented from ever developing into systemic illnesses. In the past, vaccination has been a successful means of eradicating disease. Vaccines remain a hopeful therapy for the future, but time is short,and there are many obstacles.Information regarding bioterrorism agents and their treatments comes mainly from dated data or from in vitro or animal studies that may not apply to human treatment and disease. Additionally, the current threat of bioterrorism does not allow enough time for accurate, well-designed,controlled studies in humans before the release of investigational vaccines. Furthermore, some human studies would not be safe or ethical. Finally,many members of society suffer from illnesses that would put them at high risk to receive prophylactic vaccination. It is therefore naive to believe that vaccines would be the ultimate protection from these agents. In addition to vaccine development, there must be concurrent investigations into disease management and treatment. Even in instances in which vaccination is known to be an effective means of disease protection. biologic agents may be presented in a manner that renders vaccines ineffective. Virulent strains of organisms may be used, more than one organism may be used in tandem to increase virulence, and strains may be selected for antibiotic and vaccine resistance. Genetically engineered strains may use virulence factors other than those targeted in vaccines, and high

  16. Clinical development of intramuscular electroporation: providing a "boost" for DNA vaccines.

    Science.gov (United States)

    Khan, Amir S; Broderick, Kate E; Sardesai, Niranjan Y

    2014-01-01

    The development of effective vaccines has helped to eradicate or control the spread of numerous infectious diseases. However, there are many more diseases that have proved more difficult to eliminate using conventional vaccines. The recent innovation of DNA vaccines may provide a "boost" to the development efforts. While the early efforts of DNA vaccines in the clinic were disappointing, the use of in vivo electroporation has helped to provide some basis for optimism. Now, there are several ongoing clinical studies of vaccines against such diseases as malaria, HIV, hepatitis C, and even various types of cancer. This review will highlight three recently published clinical studies using intramuscular DNA administration with electroporation.

  17. 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

    2017-02-23

    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.

  18. Dengue vaccine development: strategies and challenges.

    Science.gov (United States)

    Ramakrishnan, Lakshmy; Pillai, Madhavan Radhakrishna; Nair, Radhakrishnan R

    2015-03-01

    Infection with dengue virus may result in dengue fever or a more severe outcome, such as dengue hemorrhagic syndrome/shock. Dengue virus infection poses a threat to endemic regions for four reasons: the presence of four serotypes, each with the ability to cause a similar disease outcome, including fatality; difficulties related to vector control; the lack of specific treatment; and the nonavailability of a suitable vaccine. Vaccine development is considered challenging due to the severity of the disease observed in individuals who have acquired dengue-specific immunity, either passively or actively. Therefore, the presence of vaccine-induced immunity against a particular serotype may prime an individual to severe disease on exposure to dengue virus. Vaccine development strategies include live attenuated vaccines, chimeric, DNA-based, subunit, and inactivated vaccines. Each of the candidates is in various stages of preclinical and clinical development. Issues pertaining to selection pressures, viral interaction, and safety still need to be evaluated in order to induce a complete protective immune response against all four serotypes. This review highlights the various strategies that have been employed in vaccine development, and identifies the obstacles to producing a safe and effective vaccine.

  19. Vaccine development using recombinant DNA technology

    Science.gov (United States)

    Vaccines induce an immune response in the host that subsequently recognizes infectious agents and helps fight off the disease; vaccines must do this without causing the disease. This paper reviews the development of recombinant DNA technologies as a means of providing new ways for attenuating diseas...

  20. Nonclinical Development of BCG Replacement Vaccine Candidates

    Directory of Open Access Journals (Sweden)

    Bernd Eisele

    2013-04-01

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

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

    Directory of Open Access Journals (Sweden)

    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

  2. Cancer Vaccine by Fusions of Dendritic and Cancer Cells

    Directory of Open Access Journals (Sweden)

    Shigeo Koido

    2009-01-01

    Full Text Available Dendritic cells (DCs are potent antigen-presenting cells and play a central role in the initiation and regulation of primary immune responses. Therefore, their use for the active immunotherapy against cancers has been studied with considerable interest. The fusion of DCs with whole tumor cells represents in many ways an ideal approach to deliver, process, and subsequently present a broad array of tumor-associated antigens, including those yet to be unidentified, in the context of DCs-derived costimulatory molecules. DCs/tumor fusion vaccine stimulates potent antitumor immunity in the animal tumor models. In the human studies, T cells stimulated by DC/tumor fusion cells are effective in lysis of tumor cells that are used as the fusion partner. In the clinical trials, clinical and immunological responses were observed in patients with advanced stage of malignant tumors after being vaccinated with DC/tumor fusion cells, although the antitumor effect is not as vigorous as in the animal tumor models. This review summarizes recent advances in concepts and techniques that are providing new impulses to DCs/tumor fusions-based cancer vaccination.

  3. Accelerated vaccine development against emerging infectious diseases.

    Science.gov (United States)

    Leblanc, Pierre R; Yuan, Jianping; Brauns, Tim; Gelfand, Jeffrey A; Poznansky, Mark C

    2012-07-01

    Emerging and re-emerging infectious diseases represent a major challenge to vaccine development since it involves two seemingly contradictory requirements. Rapid and flexible vaccine generation while using technologies and processes that can facilitate accelerated regulatory review. Development in the "-omics" in combination with advances in vaccinology offer novel opportunities to meet these requirements. Here we describe how a consortium of five different organizations from academia and industry is addressing these challenges. This novel approach has the potential to become the new standard in vaccine development allowing timely deployment to avert potential pandemics.

  4. 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.

  5. Recombinant vaccines and the development of new vaccine strategies.

    Science.gov (United States)

    Nascimento, I P; Leite, L C C

    2012-12-01

    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.

  6. Recombinant vaccines and the development of new vaccine strategies

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-09-07

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

  7. Protein Crystallography in Vaccine Research and Development.

    Science.gov (United States)

    Malito, Enrico; Carfi, Andrea; Bottomley, Matthew J

    2015-06-09

    The use of protein X-ray crystallography for structure-based design of small-molecule drugs is well-documented and includes several notable success stories. However, it is less well-known that structural biology has emerged as a major tool for the design of novel vaccine antigens. Here, we review the important contributions that protein crystallography has made so far to vaccine research and development. We discuss several examples of the crystallographic characterization of vaccine antigen structures, alone or in complexes with ligands or receptors. We cover the critical role of high-resolution epitope mapping by reviewing structures of complexes between antigens and their cognate neutralizing, or protective, antibody fragments. Most importantly, we provide recent examples where structural insights obtained via protein crystallography have been used to design novel optimized vaccine antigens. This review aims to illustrate the value of protein crystallography in the emerging discipline of structural vaccinology and its impact on the rational design of vaccines.

  8. Vaccines in Development against West Nile Virus

    Directory of Open Access Journals (Sweden)

    Frederic Tangy

    2013-09-01

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

  9. Development of Vaccines for Chikungunya Fever.

    Science.gov (United States)

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

    2016-12-15

    Chikungunya fever, an acute and often chronic arthralgic disease caused by the mosquito-borne chikungunya virus (CHIKV), has reemerged since 2004 to cause millions of cases. Because CHIKV exhibits limited antigenic diversity and is not known to be capable of reinfection, a vaccine could serve to both prevent disease and diminish human amplification during epidemic circulation. Here, we review the many promising vaccine platforms and candidates developed for CHIKV since the 1970s, including several in late preclinical or clinical development. We discuss the advantages and limitations of each, as well as the commercial and regulatory challenges to bringing a vaccine to market.

  10. 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 sex-specif

  11. Status of vaccine research and development of vaccines for GBS.

    Science.gov (United States)

    Heath, Paul T

    2016-06-03

    Streptococcus agalactiae (group B streptococcus (GBS)) is the leading cause of neonatal sepsis and meningitis in many countries. Intrapartum antibiotic strategies have reduced the incidence of early-onset neonatal GBS in a number of countries but have had no impact on late onset GBS infection (LOD). In low/middle income settings, the disease burden remains uncertain although in several countries of Southern Africa appears comparable to or higher than that of high-income countries. As disease may be rapidly fulminating cases can be missed before appropriate samples are obtained and this may lead to underestimation of the true burden. Given the rapid onset and progression within hours of birth as well as the deficiencies in IAP strategies and absence of a solution for preventing LOD, it is clear that administration of a suitable vaccine in pregnancy could provide a better solution in all settings; it should also be cost effective. The current leading vaccine candidates are CPS-protein conjugate vaccines but protein-based vaccines are also in development and one has recently commenced clinical trials.

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

    Science.gov (United States)

    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.

  13. Carcinoembryonic antigen (CEA)-based cancer vaccines: recent patents and antitumor effects from experimental models to clinical trials.

    Science.gov (United States)

    Turriziani, Mario; Fantini, Massimo; Benvenuto, Monica; Izzi, Valerio; Masuelli, Laura; Sacchetti, Pamela; Modesti, Andrea; Bei, Roberto

    2012-09-01

    Carcinoembryonic antigen (CEA), a glycosylated protein of MW 180 kDa, is overexpressed in a wide range of human carcinomas, including colorectal, gastric, pancreatic, non-small cell lung and breast carcinomas. Accordingly, CEA is one of several oncofetal antigens that may serve as a target for active anti-cancer specific immunotherapy. Experimental results obtained by employing animal models have supported the design of clinical trials using a CEA-based vaccine for the treatment of different types of human cancers. This review reports findings from experimental models and clinical evidence on the use of a CEA-based vaccine for the treatment of cancer patients. Among the diverse CEA-based cancer vaccines, DCs- and recombinant viruses-based vaccines seem the most valid. However, although vaccination was shown to induce a strong immune response to CEA, resulting in a delay in tumor progression and prolonged survival in some cancer patients, it failed to eradicate the tumor in most cases, owing partly to the negative effect exerted by the tumor microenvironment on immune response. Thus, in order to develop more efficient and effective cancer vaccines, it is necessary to design new clinical trials combining cancer vaccines with chemotherapy, radiotherapy and drugs which target those factors responsible for immunosuppression of immune cells. This review also discusses relevant patents relating to the use of CEA as a cancer vaccine.

  14. Nanovaccines: recent developments in vaccination

    Indian Academy of Sciences (India)

    Tarala D Nandedkar

    2009-12-01

    In the past 100 years, vaccination has contributed immensely to public health by preventing a number of infectious diseases. Attenuated, killed or part of the microorganism is employed to stimulate the immune system against it. Progress in biotechnology has provided protective immunity through DNA vaccines. In recent years, nanovaccine is a novel approach to the methodology of vaccination. Nanomaterials are delivered in the form of microspheres, nanobeads or micro-nanoprojections. Painless, effective and safe needle-free routes such as the intranasal or the oral route, or patches of microprojections to the skin are some of the approaches which are in the experimental stage at present but may have a great future ahead in nanovaccination.

  15. The Development of an AIDS Mucosal Vaccine

    Directory of Open Access Journals (Sweden)

    Xian Tang

    2010-01-01

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

  16. Tularemia vaccine development: paralysis or progress?

    Directory of Open Access Journals (Sweden)

    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

  17. Tularemia vaccine development: paralysis or progress?

    Science.gov (United States)

    Sunagar, Raju; Kumar, Sudeep; Franz, Brian J; Gosselin, Edmund J

    2016-01-01

    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. PMID:27200274

  18. Recent advances in design of immunogenic and effective naked DNA vaccines against cancer.

    Science.gov (United States)

    Fioretti, Daniela; Iurescia, Sandra; Rinaldi, Monica

    2014-01-01

    A variety of clinical trials for vaccines against cancer have provided evidence that DNA vaccines are well tolerated and have an excellent safety profile. DNA vaccines require much improvement to make them sufficiently effective against cancer in the clinic. Nowadays, it is clear that an increased antigen expression correlates with improved immunogenicity and it is critical to vaccine performance in large animals and humans. Similarly, additional strategies are required to activate effective immunity against poorly immunogenic tumour antigens. This review discusses very recent scientific references focused on the development of sophisticated DNA vaccines against cancer. We report a selection of novel and relevant patents employed to improve their immunogenicity through several strategies such as the use of tissue-specific transcriptional elements, nuclear localisation signalling, codon-optimisation and by targeting antigenic proteins to secretory pathway. Recent patents validating portions or splice variants of tumour antigens as candidates for cancer DNA vaccines with improved specificity, such as mesothelin and hTERT, are also discussed. Lastly, we review novel patents on the use of genetic immunomodulators, such as "universal" T helper epitopes derived from tetanus toxin, E. coli heat labile enterotoxin and vegetable proteins, as well as cytokines, chemokines or costimulatory molecules such as IL-6, IL-15, IL- 21 to amplify immunity against cancer.

  19. Prospects for the development of fungal vaccines.

    Science.gov (United States)

    Deepe, G S

    1997-10-01

    In an era that emphasizes the term "cost-effective," vaccines are the ideal solution to preventing disease at a relatively low cost to society. Much of the previous emphasis has been on childhood scourges such as measles, mumps, rubella, poliomyelitis, and Haemophilus influenzae type b. The concept of vaccines for fungal diseases has had less impact because of the perceived limited problem. However, fungal diseases have become increasingly appreciated as serious medical problems that require recognition and aggressive management. The escalation in the incidence and prevalence of infection has prompted a renewed interest in vaccine development. Herein, I discuss the most recent developments in the search for vaccines to combat fungal infections. Investigators have discovered several inert substances from various fungi that can mediate protection in animal models. The next challenge will be to find the suitable mode of delivery for these immunogens.

  20. Vaccination Against Dengue: Challenges and Current Developments.

    Science.gov (United States)

    Guy, Bruno; Lang, Jean; Saville, Melanie; Jackson, Nicholas

    2016-01-01

    Dengue is a growing threat worldwide, and the development of a vaccine is a public health priority. The completion of the active phase of two pivotal efficacy studies conducted in Asia and Latin America by Sanofi Pasteur has constituted an important step. Several other approaches are under development, and whichever technology is used, vaccine developers face several challenges linked to the particular nature and etiology of dengue disease. We start our review by defining questions and potential issues linked to dengue pathology and presenting the main types of vaccine approaches that have explored these questions; some of these candidates are in a late stage of clinical development. In the second part of the review, we focus on the Sanofi Pasteur dengue vaccine candidate, describing the steps from research to phase III efficacy studies. Finally, we discuss what could be the next steps, before and after vaccine introduction, to ensure that the vaccine will provide the best benefit with an acceptable safety profile to the identified target populations.

  1. Developing effective tumor vaccines:basis,challenges and perspectives

    Institute of Scientific and Technical Information of China (English)

    XU Qingwen; CHEN Weifeng

    2007-01-01

    A remarkable advance in tumor immunology during the last decade is the elucidation of the antigenic basis of tumor recognition and destruction.A variety of tumor antigens have been identified using several strategies including conventional experiments and newly developed bioinformatics.Among these antigens,cancer/testis antigen (CT antigen) is considered to be the most promising target for immunotherapy by vaccination.Successful immunotherapy of tumors requires understanding of the natural relationship between the immune system and tumor in the status of differentiation,invasion and maturation.Continued progress in development of effective cancer vaccines depends on the identification of appropriate target antigens,the establishment of optimal immunization strategies without harmful autoimmune responses and the ability of manipulating tumor microenvironment to circumvent immune suppression and to augment the anti-tumor immune response.

  2. 78 FR 11895 - Prospective Grant of Exclusive License: Development of MUC-1 Tumor Associated Antigens as Cancer...

    Science.gov (United States)

    2013-02-20

    ... Rights for development of Pox-virus based vaccines for bladder cancer, breast cancer, colorectal cancer... HUMAN SERVICES National Institutes of Health Prospective Grant of Exclusive License: Development of MUC-1 Tumor Associated Antigens as Cancer Vaccines for Bladder Cancer, Breast Cancer, Colorectal...

  3. GENERAL AWARNANCE OF HUMAN PAPILLOMA VIRUS VACCINE AGAINST CERVICAL CANCER

    Directory of Open Access Journals (Sweden)

    SAFILA NAVEED

    2014-01-01

    Full Text Available We have conducted a survey program on the awarnance of HPV vaccine of cervical cancer in common people. Methods: For this survey we perform 2 steps. First we made a questionnaires in which we ask to female of different belongs to different education field either they are married or not. Secondly we gone in the different hospitals of Karachi and observe treatment, diagnosis, vaccination availability and frequency of cervical cancer. Results:From questionnaire we observed that only 1 % female are aware about cervical cancer and its vaccine i.e. HPV, even female belongs medical field are not aware about it. Form hospital survey we observed that frequency of cervical cancer is very less but in Shaukat Khanum hospital 90 cases reported out of 1803 cancer. The given treatment is radiology, chemotherapy and surgery.

  4. Workshop report: Schistosomiasis vaccine clinical development and product characteristics.

    Science.gov (United States)

    Mo, Annie X; Colley, Daniel G

    2016-02-17

    A schistosomiasis vaccine meeting was organized to evaluate the utility of a vaccine in public health programs, to discuss clinical development paths, and to define basic product characteristics for desirable vaccines to be used in the context of schistosomiasis control and elimination programs. It was concluded that clinical evaluation of a schistosomiasis vaccine is feasible with appropriate trial design and tools. Some basic Preferred Product Characteristics (PPC) for a human schistosomiasis vaccine and for a veterinary vaccine for bovine use were also proposed.

  5. Preclinical development of HIvax: Human survivin highly immunogenic vaccines.

    Science.gov (United States)

    Hoffmann, Peter R; Panigada, Maddalena; Soprana, Elisa; Terry, Frances; Bandar, Ivo Sah; Napolitano, Andrea; Rose, Aaron H; Hoffmann, Fukun W; Ndhlovu, Lishomwa C; Belcaid, Mahdi; Moise, Lenny; De Groot, Anne S; Carbone, Michele; Gaudino, Giovanni; Matsui, Takashi; Siccardi, Antonio; Bertino, Pietro

    2015-01-01

    Our previous work involved the development of a recombinant fowlpox virus encoding survivin (FP-surv) vaccine that was evaluated for efficacy in mesothelioma mouse models. Results showed that FP-surv vaccination generated significant immune responses, which led to delayed tumor growth and improved animal survival. We have extended those previous findings in the current study, which involves the pre-clinical development of an optimized version of FP-surv designed for human immunization (HIvax). Survivin-derived peptides for the most common haplotypes in the human population were identified and their immunogenicity confirmed in co-culture experiments using dendritic cells and T cells isolated from healthy donors. Peptides confirmed to induce CD8(+) and CD4(+) T cells activation in humans were then included in 2 transgenes optimized for presentation of processed peptides on MHC-I (HIvax1) and MHC-II (HIvax2). Fowlpox vectors expressing the HIvax transgenes were then generated and their efficacy was evaluated with subsequent co-culture experiments to measure interferon-γ and granzyme B secretion. In these experiments, both antigen specific CD4(+) and CD8(+) T cells were activated by HIvax vaccines with resultant cytotoxic activity against survivin-overexpressing mesothelioma cancer cells. These results provide a rationale for clinical testing of HIvax1 and HIvax2 vaccines in patients with survivin-expressing cancers.

  6. Bacterial otitis media: current vaccine development strategies.

    Science.gov (United States)

    Cripps, Allan W; Kyd, Jennelle

    2003-02-01

    Otitis media is the most common reason for children less than 5 years of age to visit a medical practitioner. Whilst the disease rarely results in death, there is significant associated morbidity. The most common complication is loss of hearing at a critical stage of the development of speech, language and cognitive abilities in children. The cause and pathogenesis of otitis media is multifactorial. Among the contributing factors, the single most important are viral and bacterial infections. Infection with respiratory syncytial virus, influenza viruses, para-influenza viruses, enteroviruses and adenovirus are most commonly associated with acute and chronic otitis media. Streptococcus pneumoniae, non-typeable Haemophilus influenzae and Moraxella catarrhalis are the most commonly isolated bacteria from the middle ears of children with otitis media. Treatment of otitis media has largely relied on the administration of antimicrobials and surgical intervention. However, attention has recently focused on the development of a vaccine. For a vaccine to be effective against bacterial otitis media, it must, at the very least, contain antigens that induce a protective immune response in the middle ear against the three most common infecting bacteria. Whilst over the past decade there has been significant progress in the development of vaccines against invasive S. pneumoniae disease, these vaccines are less efficacious for otitis media. The search for candidate vaccine antigens for non-typeable H. influenzae are well advanced whilst less progress has been made for M. catarrhalis. No human studies have been conducted for non-typeable H. influenzae or M. catarrhalis and the concept of a tribacterial vaccine remains to be tested in animal models. Only when vaccine antigens are determined and an understanding of the immune responses induced in the middle ear by infection and immunization is gained will the formulation of a tribacterial vaccine against otitis media be possible.

  7. NGcGM3 Ganglioside: A Privileged Target for Cancer Vaccines

    Directory of Open Access Journals (Sweden)

    Luis E. Fernandez

    2010-01-01

    Full Text Available Active specific immunotherapy is a promising field in cancer research. N-glycolyl (NGc gangliosides, and particularly NGcGM3, have received attention as a privileged target for cancer therapy. Many clinical trials have been performed with the anti-NGc-containing gangliosides anti-idiotype monoclonal antibody racotumomab (formerly known as 1E10 and the conjugated NGcGM3/VSSP vaccine for immunotherapy of melanoma, breast, and lung cancer. The present paper examines the role of NGc-gangliosides in tumor biology as well as the available preclinical and clinical data on these vaccine products. A brief discussion on the relevance of prioritization of cancer antigens in vaccine development is also included.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    Maha Zohra eLadjemi

    2012-11-01

    Full Text Available Since the discovery of tumor-associated antigens (TAA, 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 (eg. 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 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-idiotypic (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.

  11. Development of stable influenza vaccine powder formulations: challenges and possibilities.

    Science.gov (United States)

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

    2008-06-01

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

  12. Vaccine development for tuberculosis: current progress.

    Science.gov (United States)

    Orme, Ian M

    2013-07-01

    Very substantial efforts have been made over the past decade or more to develop vaccines against tuberculosis. Historically, this began with a view to replace the current vaccine, Bacillus Calmette Guérin (BCG), but more recently most candidates are either new forms of this bacillus, or are designed to boost immunity in children given BCG as infants. Good progress is being made, but very few have, as yet, progressed into clinical trials. The leading candidate has advanced to phase IIb efficacy testing, with disappointing results. This article discusses the various types of vaccines, including those designed to be used in a prophylactic setting, either alone or BCG-boosting, true therapeutic (post-exposure) vaccines, and therapeutic vaccines designed to augment chemotherapy. While there is no doubt that progress is still being made, we have a growing awareness of the limitations of our animal model screening processes, further amplified by the fact that we still do not have a clear picture of the immunological responses involved, and the precise type of long-lived immunity that effective new vaccines will need to induce.

  13. Vaccine development for tuberculosis: current progress

    Science.gov (United States)

    Orme, Ian M.

    2013-01-01

    Very substantial efforts have been made over the past decade or more to develop vaccines against tuberculosis. Historically, this began with a view to replace the current vaccine, BCG, but more recently most candidates are either new forms of this bacillus, or are designed to boost immunity in children given BCG as infants. Good progress is being made, but very few have as yet progressed into clinical trials. The leading candidate has advanced to Phase IIb efficacy testing, with disappointing results. This article discusses the various types of vaccines, including those designed to be used in a prophylactic setting, either alone or BCG-boosting, true therapeutic [post-exposure] vaccines, and therapeutic vaccines designed to augment chemotherapy. While there is no doubt that progress is still being made, we have a growing awareness of the limitations of our animal model screening processes, further amplified by the fact that we still do not have a clear picture of the immunological responses involved, and the precise type of long lived immunity we will need effective new vaccines to induce. PMID:23794129

  14. Vaccine-based clinical trials in ovarian cancer

    NARCIS (Netherlands)

    Leffers, Ninke; Daemen, Toos; Boezen, H. Marike; Melief, Kees J. M.; Nijman, Hans W.

    2011-01-01

    Ovarian cancer vaccines are one of the new treatment strategies under investigation in epithelial ovarian cancer. This article discusses the results of different immunization strategies, points out potential pitfalls in study designs and provides possible solutions for augmentation of clinical effic

  15. Development of vaccines for Plasmodium vivax malaria.

    Science.gov (United States)

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

    2015-12-22

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

  16. The expanding vaccine development pipeline, 1995-2008.

    Science.gov (United States)

    Davis, Matthew M; Butchart, Amy T; Coleman, Margaret S; Singer, Dianne C; Wheeler, John R C; Pok, Angela; Freed, Gary L

    2010-02-03

    Successful launches of recently licensed vaccines contrast with pharmaceutical industry concerns about unfavorable market conditions, making the status and future of vaccine development uncertain. We assessed trends in private-sector vaccine research and development for the period 1995-2008, using a global pharmaceutical database to identify prophylactic vaccines in preclinical, Phase I, Phase II, or Phase III stages of development. We counted companies that research and/or manufacture vaccines ("vaccine originators") and their vaccine products in each year. The global number of vaccine originators doubled (to 136), as did the number of prophylactic vaccine products in development (to 354); the majority of this growth was in preclinical and early phase clinical research. Because rapid growth in earlier research phases has not yet led to growth in Phase III, it is not yet clear whether recent industry expansion will translate to an increase in the number of available vaccines in the near future.

  17. Glycan changes: cancer metastasis and anti-cancer vaccines

    Indian Academy of Sciences (India)

    Min Li; Lujun Song; Xinyu Qin

    2010-12-01

    Complex carbohydrates, which are major components of the cell membrane, perform important functions in cell–cell and cell–extracellular matrix interactions, as well as in signal transduction. They comprise three kinds of biomolecules: glycoproteins, proteoglycans and glycosphingolipids. Recent studies have also shown that glycan changes in malignant cells take a variety of forms and mediate key pathophysiological events during the various stages of tumour progression. Glycosylation changes are universal hallmarks of malignant transformation and tumour progression in human cancer, which take place on the whole cells or some specific molecules. Accordingly, those changes make them prominent candidates for cancer biomarkers in the meantime. This review mainly focuses on the correlation between glycosylation and the metastasis potential of tumour cells from comprehensive aspects to further address the vital roles of glycans in oncogenesising. Moreover, utilizing these glycosylation changes to ward off tumour metastasis by means of anti-adhesion approach or devising anti-cancer vaccine is one of promising targets of future study.

  18. In situ vaccination: Cancer immunotherapy both personalized and off-the-shelf.

    Science.gov (United States)

    Hammerich, Linda; Binder, Adam; Brody, Joshua D

    2015-12-01

    As cancer immunotherapy continues to benefit from novel approaches which cut immune 'brake pedals' (e.g. anti-PD1 and anti-CTLA4 antibodies) and push immune cell gas pedals (e.g. IL2, and IFNα) there will be increasing need to develop immune 'steering wheels' such as vaccines to guide the immune system specifically toward tumor associated antigens. Two primary hurdles in cancer vaccines have been: identification of universal antigens to be used in 'off-the-shelf' vaccines for common cancers, and 2) logistical hurdles of ex vivo production of individualized whole tumor cell vaccines. Here we summarize approaches using 'in situ vaccination' in which intratumoral administration of off-the-shelf immunomodulators have been developed to specifically induce (or amplify) T cell responses to each patient's individual tumor. Clinical studies have confirmed the induction of systemic immune and clinical responses to such approaches and preclinical models have suggested ways to further potentiate the translation of in situ vaccine trials for our patients.

  19. Immunological Evaluation of Recent MUC1 Glycopeptide Cancer Vaccines

    Directory of Open Access Journals (Sweden)

    Md Kamal Hossain

    2016-07-01

    Full Text Available Aberrantly glycosylated mucin 1 (MUC1 is a recognized tumor-specific antigen on epithelial cell tumors. A wide variety of MUC1 glycopeptide anti-cancer vaccines have been formulated by many research groups. Some researchers have used MUC1 alone as an immunogen whereas other groups used different antigenic carrier proteins such as bovine serum albumin or keyhole limpet hemocyanin for conjugation with MUC1 glycopeptide. A variety of adjuvants have been used with MUC1 glycopeptides to improve their immunogenicity. Fully synthetic multicomponent vaccines have been synthesized by incorporating different T helper cell epitopes and Toll-like receptor agonists. Some vaccine formulations utilized liposomes or nanoparticles as vaccine delivery systems. In this review, we discuss the immunological evaluation of different conjugate or synthetic MUC1 glycopeptide vaccines in different tumor or mouse models that have been published since 2012.

  20. Freund's vaccine adjuvant promotes Her2/Neu breast cancer

    Directory of Open Access Journals (Sweden)

    Woditschka Stephan

    2009-01-01

    Full Text Available Abstract Background 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. Methods 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. Results 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. Conclusion 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.

  1. Immunoinformatics of Placental Malaria Vaccine Development

    DEFF Research Database (Denmark)

    Jessen, Leon Eyrich

    for the pathogenesis of PM was identified as the P. falciparum Erythrocyte Membrane Protein 1 (Pf EMP1) variant VAR2CSA. VAR2CSA is the leading candidate for a vaccine against PM. The thesis is divided into 4 parts, where part I provide the reader with an introduction and background for the subjects covered......CSA-DBL5ε sequences each with associated phenotypes. Immunity towards PM is gradually acquired, therefore if a given sequence motif can be phenotype-correlated then the motif may be involved in VAR2CSA immunogenecity. Motifs defining VAR2CSA immunogenecity are naturally interesting in vaccine...... and development in the field of placental malaria vaccine development....

  2. Development of Vaccines against Visceral Leishmaniasis

    Directory of Open Access Journals (Sweden)

    Krystal J. Evans

    2012-01-01

    Full Text Available Leishmaniasis is a neglected disease resulting in a global morbidity of 2,090 thousand Disability-Adjusted Life Years and a mortality rate of approximately 60,000 per year. Among the three clinical forms of leishmaniasis (cutaneous, mucosal, and visceral, visceral leishmaniasis (VL accounts for the majority of mortality, as if left untreated VL is almost always fatal. Caused by infection with Leishmania donovani or L. infantum, VL represents a serious public health problem in endemic regions and is rapidly emerging as an opportunistic infection in HIV patients. To date, no vaccine exists for VL or any other form of leishmaniasis. In endemic areas, the majority of those infected do not develop clinical symptoms and past infection leads to robust immunity against reinfection. Thus the development of vaccine for Leishmania is a realistic public health goal, and this paper summarizes advances in vaccination strategies against VL.

  3. 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.

  4. 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.

  5. 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

  6. Paradigm shifting vaccines: prophylactic vaccines against latent varicella-zoster virus infection and against HPV-associated cancer

    OpenAIRE

    Frazer, Ian H.; Levin, Myron J.

    2011-01-01

    We compare the design, mechanism of action, and clinical efficacy of two recently licensed paradigm shifting vaccines. Zostavax is the first vaccine licensed to prevent disease in patients already infected with a pathogen, and is contrasted with Gardasil and Cervarix, the first vaccines designed and licensed specifically to prevent cancers.

  7. 76 FR 68768 - Guidance for Industry: Clinical Considerations for Therapeutic Cancer Vaccines; Availability

    Science.gov (United States)

    2011-11-07

    ... No. FDA-2009-D-0427] Guidance for Industry: Clinical Considerations for Therapeutic Cancer Vaccines... Considerations for Therapeutic Cancer Vaccines'' dated October 2011. The guidance document provides sponsors who wish to submit an Investigational New Drug application (IND) for a therapeutic cancer vaccine...

  8. Therapeutic cancer vaccines in combination with conventional therapy

    DEFF Research Database (Denmark)

    Junker, Niels; Ellebaek, Eva; Svane, Inge Marie

    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...... of proteins coupled to intrinsic properties of cancer cells. For example, proteins associated with drug resistance can be targeted, and form ideal target structures for use in combination with chemotherapy for killing of surviving drug resistant cancer cells. Proteins associated with the malignant phenotype...... can be targeted to specifically target cancer cells, but proteins targeted by immunotherapy may also simultaneously target cancer cells as well as suppressive cells in the tumor stroma....

  9. 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...... can be targeted to specifically target cancer cells, but proteins targeted by immunotherapy may also simultaneously target cancer cells as well as suppressive cells in the tumor stroma....... of proteins coupled to intrinsic properties of cancer cells. For example, proteins associated with drug resistance can be targeted, and form ideal target structures for use in combination with chemotherapy for killing of surviving drug resistant cancer cells. Proteins associated with the malignant phenotype...

  10. Intra-Prostate Cancer Vaccine Inducer

    Science.gov (United States)

    2006-07-01

    immu- nogenicity while normal antigens are tolerated during development and are of much weaker im- munogenicity. (2) Autoimmunity induction is or...RF, Barr H, et al. Palliation of patients with dysphagia due to advanced esophageal cancer by endoscopic injection of cisplatin/epinephrine injectable...SA, McCormack NA, Lavender D, Haworth R. The assessment of local tolerance , acute toxicity, and DNA biodistribution following particle-mediated

  11. Vaccines against human papillomavirus and perspectives for the prevention and control of cervical cancer

    Directory of Open Access Journals (Sweden)

    García-Carrancá Alejandro

    2003-01-01

    Full Text Available Today, "persistent" infections by certain types of human papillomavirus (HPV are considered necessary for developing cervical cancer. Producing efficient vaccines against these viruses may eventually lead to a great reduction in incidence and mortality rates of this cancer. In the case of HPV, the production of traditional vaccines usually based in dead or attenuated viruses is not possible due in part to the lack of systems where large quantities of viral particles could be obtained. Fortunately, the expression of the late L1 protein alone, or in combination with L2, leads to the generation of structures resembling true virions that have been called virus-like particles (VLPs and constitute excellent candidates as prophylactic vaccines. VLPs have shown to be very immunogenic, and have prevented development of natural or challenged infections in both animal systems and humans. Recently, HPV16 VLPs were shown to be very efficient to prevent the development of "persistent" infections, as determined by PCR assays, in a large group of vaccinated women. Therapeutic vaccines, on the other hand, are expected to have an impact on advanced lesions and residual illness, by taking advantaje of the fact that early E6 and E7 genes are thought to be constitutively expressed in cervical tumors and precursor lesions. Finally, DNA-based vaccines could represent a useful alternative for preventing infections by genital HPV.

  12. Prophylactic vaccination targeting ERBB3 decreases polyp burden in a mouse model of human colorectal cancer

    Science.gov (United States)

    Bautz, David J.; Sherpa, Ang T.

    2017-01-01

    ABSTRACT Prophylactic vaccination is typically utilized for the prevention of communicable diseases such as measles and influenza but, with the exception of vaccines to prevent cervical cancer, is not widely used as a means of preventing or reducing the incidence of cancer. Here, we utilize a peptide-based immunotherapeutic approach targeting ERBB3, a pseudo-kinase member of the EGFR/ERBB family of receptor tyrosine kinases, as a means of preventing occurrence of colon polyps. Administration of the peptide resulted in a significant decrease in the development of intestinal polyps in C57BL/6J-ApcMin mice, a model of familial adenomatous polyposis (FAP). In addition, even though they were not vaccinated, ApcMin offspring born to vaccinated females developed significantly fewer polyps than offspring born to control females. Lastly, to validate ERBB as a valid target for vaccination, we found no overt toxicity, increases in apoptosis, or morphological changes in tissues where Erbb3 was ablated in adult mice. These results indicate that prophylactic vaccination targeting ERBB3 could prevent the development of colon polyps in an at-risk patient population.

  13. Tuberculosis Vaccines – state of the art, and novel approaches to vaccine development

    Directory of Open Access Journals (Sweden)

    Christopher da Costa

    2015-03-01

    Full Text Available The quest for a vaccine that could have a major impact in reducing the current global burden of TB disease in humans continues to be extremely challenging. Significant gaps in our knowledge and understanding of the pathogenesis and immunology of tuberculosis continue to undermine efforts to break new ground, and traditional approaches to vaccine development have thus far met with limited success. Existing and novel candidate vaccines are being assessed in the context of their ability to impact the various stages that culminate in disease transmission and an increase in the global burden of disease. Innovative methods of vaccine administration and delivery have provided a fresh stimulus to the search for the elusive vaccine. Here we discuss the current status of preclinical vaccine development, providing insights into alternative approaches to vaccine delivery and promising candidate vaccines. The state of the art of clinical development also is reviewed.

  14. Status of vaccine research and development of vaccines for Chlamydia trachomatis infection.

    Science.gov (United States)

    Poston, Taylor B; Gottlieb, Sami L; Darville, Toni

    2017-01-19

    Genital infection with Chlamydia trachomatis, a gram-negative obligate intracellular bacterium, is the most common bacterial sexually transmitted infection globally. Ascension of chlamydial infection to the female upper genital tract can cause acute pelvic inflammatory disease, tubal factor infertility, ectopic pregnancy, and chronic pelvic pain. Shortcomings of current chlamydia control strategies, especially for low- and middle-income countries, highlight the need for an effective vaccine. Evidence from animal models, human epidemiological studies, and early trachoma vaccine trials suggest that a C. trachomatis vaccine is feasible. Vaccine development for genital chlamydial infection has been in the preclinical phase of testing for many years, but the first Phase I trials of chlamydial vaccine candidates are underway, and scientific advances hold promise for additional candidates to enter clinical evaluation in the coming years. We describe the clinical and public health need for a C. trachomatis vaccine, provide an overview of Chlamydia vaccine development efforts, and summarize current vaccine candidates in the development pipeline.

  15. Tuberculosis vaccines--state of the art, and novel approaches to vaccine development.

    Science.gov (United States)

    da Costa, Christopher; Walker, Barry; Bonavia, Aurelio

    2015-03-01

    The quest for a vaccine that could have a major impact in reducing the current global burden of TB disease in humans continues to be extremely challenging. Significant gaps in our knowledge and understanding of the pathogenesis and immunology of tuberculosis continue to undermine efforts to break new ground, and traditional approaches to vaccine development have thus far met with limited success. Existing and novel candidate vaccines are being assessed in the context of their ability to impact the various stages that culminate in disease transmission and an increase in the global burden of disease. Innovative methods of vaccine administration and delivery have provided a fresh stimulus to the search for the elusive vaccine. Here we discuss the current status of preclinical vaccine development, providing insights into alternative approaches to vaccine delivery and promising candidate vaccines. The state of the art of clinical development also is reviewed.

  16. TAA Polyepitope DNA-Based Vaccines: A Potential Tool for Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Roberto Bei

    2010-01-01

    Full Text Available DNA-based cancer vaccines represent an attractive strategy for inducing immunity to tumor associated antigens (TAAs in cancer patients. The demonstration that the delivery of a recombinant plasmid encoding epitopes can lead to epitope production, processing, and presentation to CD8+ T-lymphocytes, and the advantage of using a single DNA construct encoding multiple epitopes of one or more TAAs to elicit a broad spectrum of cytotoxic T-lymphocytes has encouraged the development of a variety of strategies aimed at increasing immunogenicity of TAA polyepitope DNA-based vaccines. The polyepitope DNA-based cancer vaccine approach can (a circumvent the variability of peptide presentation by tumor cells, (b allow the introduction in the plasmid construct of multiple immunogenic epitopes including heteroclitic epitope versions, and (c permit to enroll patients with different major histocompatibility complex (MHC haplotypes. This review will discuss the rationale for using the TAA polyepitope DNA-based vaccination strategy and recent results corroborating the usefulness of DNA encoding polyepitope vaccines as a potential tool for cancer therapy.

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

    Directory of Open Access Journals (Sweden)

    Stephen J Kent

    2010-09-01

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

  18. Gene gun delivery systems for cancer vaccine approaches.

    Science.gov (United States)

    Aravindaram, Kandan; Yang, Ning Sun

    2009-01-01

    Gene-based immunization with transgenic DNA vectors expressing tumor-associated antigens (TAA), cytokines, or chemokines, alone or in combination, provides an attractive approach to increase the cytotoxic T cell immunity against various cancer diseases. With this consideration, particle-mediated or gene gun technology has been developed as a nonviral method for gene transfer into various mammalian tissues. It has been shown to induce both humoral and cell-mediated immune responses in both small and large experimental animals. A broad range of somatic cell types, including primary cultures and established cell lines, has been successfully transfected ex vivo or in vitro by gene gun technology, either as suspension or adherent cultures. Here, we show that protocols and techniques for use in gene gun-mediated transgene delivery system for skin vaccination against melanoma using tumor-associated antigen (TAA) human gpl00 and reporter gene assays as experimental systems.

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

    Directory of Open Access Journals (Sweden)

    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

  20. Tailoring DNA vaccines: designing strategies against HER2 positive cancers

    Directory of Open Access Journals (Sweden)

    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.

  1. Arenavirus reverse genetics for vaccine development.

    Science.gov (United States)

    Ortiz-Riaño, Emilio; Cheng, Benson Yee Hin; Carlos de la Torre, Juan; Martínez-Sobrido, Luis

    2013-06-01

    Arenaviruses are important human pathogens with no Food and Drug Administration (FDA)-licensed vaccines available and current antiviral therapy being limited to an off-label use of the nucleoside analogue ribavirin of limited prophylactic efficacy. The development of reverse genetics systems represented a major breakthrough in arenavirus research. However, rescue of recombinant arenaviruses using current reverse genetics systems has been restricted to rodent cells. In this study, we describe the rescue of recombinant arenaviruses from human 293T cells and Vero cells, an FDA-approved line for vaccine development. We also describe the generation of novel vectors that mediate synthesis of both negative-sense genome RNA and positive-sense mRNA species of lymphocytic choriomeningitis virus (LCMV) directed by the human RNA polymerases I and II, respectively, within the same plasmid. This approach reduces by half the number of vectors required for arenavirus rescue, which could facilitate virus rescue in cell lines approved for human vaccine production but that cannot be transfected at high efficiencies. We have shown the feasibility of this approach by rescuing both the Old World prototypic arenavirus LCMV and the live-attenuated vaccine Candid#1 strain of the New World arenavirus Junín. Moreover, we show the feasibility of using these novel strategies for efficient rescue of recombinant tri-segmented both LCMV and Candid#1.

  2. Immunogenicity and clinical effectiveness of the trivalent inactivated influenza vaccine in immunocompromised children undergoing treatment for cancer.

    Science.gov (United States)

    Kotecha, Rishi S; Wadia, Ushma D; Jacoby, Peter; Ryan, Anne L; Blyth, Christopher C; Keil, Anthony D; Gottardo, Nicholas G; Cole, Catherine H; Barr, Ian G; Richmond, Peter C

    2016-02-01

    Influenza is associated with significant morbidity and mortality in children receiving therapy for cancer, yet recommendation for, and uptake of the seasonal vaccine remains poor. One hundred children undergoing treatment for cancer were vaccinated with the trivalent inactivated influenza vaccine according to national guidelines in 2010 and 2011. Influenza-specific hemagglutinin inhibition antibody titers were performed on blood samples taken prior to each vaccination and 4 weeks following the final vaccination. A nasopharyngeal aspirate for influenza was performed on all children who developed an influenza-like illness. Following vaccination, seroprotection and seroconversion rates were 55 and 43% for H3N2, 61 and 43% for H1N1, and 41 and 33% for B strain, respectively. Overall, there was a significant geometric mean fold increase to H3N2 (GMFI 4.56, 95% CI 3.19-6.52, P children with solid compared with hematological malignancies and in children vaccinated study population, compared with 6.8% in unvaccinated controls, providing an adjusted estimated vaccine effectiveness of 72% (95% CI -26-94%). There were no serious adverse events and a low reactogenicity rate of 3%. The trivalent inactivated influenza vaccine is safe, immunogenic, provides clinical protection and should be administered annually to immunosuppressed children receiving treatment for cancer. All children <10 years of age should receive a two-dose schedule.

  3. PROVENGE (Sipuleucel-T) in prostate cancer: the first FDA-approved therapeutic cancer vaccine.

    Science.gov (United States)

    Cheever, Martin A; Higano, Celestia S

    2011-06-01

    Sipuleucel-T (PROVENGE; Dendreon) is the first therapeutic cancer vaccine to be approved by the U.S. Food and Drug Administration. In men who have metastatic castration-resistant prostate cancer with no or minimal symptoms, sipuleucel-T prolongs median survival by 4.1 months compared with results in those treated with placebo. At 3 years, the proportion of patients in the vaccine group who were alive was 50% higher than that in the control group (31.7% versus 21.7%, respectively). Sipuleucel-T, which is designed to elicit an immune response to prostatic acid phosphatase, uses the patient's own immune system to recognize and combat his cancer. Currently, no other agents are available that offer a survival benefit for this population of asymptomatic patients who have not been treated with chemotherapy, except for docetaxel (whose inherent toxicities often lead patients and physicians to delay administration until symptoms develop). Straightforward strategies to increase the efficacy of sipuleucel-T are likely to provide even greater benefit. The preclinical and clinical development of sipuleucel-T is reviewed, and approaches to enhance efficacy are considered herein.

  4. 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

  5. Development of Burkholderia mallei and pseudomallei vaccines

    Directory of Open Access Journals (Sweden)

    Ediane Batista Silva

    2013-03-01

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

  6. Immune modulation by dendritic-cell-based cancer vaccines

    Indian Academy of Sciences (India)

    CHAITANYA KUMAR; SAKSHI KOHLI; POONAMALLE PARTHASARATHY BAPSY; ASHOK KUMAR VAID; MINISH JAIN; VENKATA SATHYA SURESH ATTILI; BANDANA SHARAN

    2017-03-01

    The interplay between host immunity and tumour cells has opened the possibility of targeting tumour cells bymodulation of the human immune system. Cancer immunotherapy involves the treatment of a tumour by utilizing therecombinant human immune system components to target the pro-tumour microenvironment or by revitalizing theimmune system with the ability to kill tumour cells by priming the immune cells with tumour antigens. In this review,current immunotherapy approaches to cancer with special focus on dendritic cell (DC)-based cancer vaccines arediscussed. Some of the DC-based vaccines under clinical trials for various cancer types are highlighted. Establishingtumour immunity involves a plethora of immune components and pathways; hence, combining chemotherapy,radiation therapy and various arms of immunotherapy, after analysing the benefits of individual therapeutic agents,might be beneficial to the patient.

  7. Development of an improved vaccine evaluation protocol to compare the efficacy of Newcastle disease vaccines.

    Science.gov (United States)

    Cardenas-Garcia, Stivalis; Diel, Diego G; Susta, Leonardo; Lucio-Decanini, Eduardo; Yu, Qingzhong; Brown, Corrie C; Miller, Patti J; Afonso, Claudio L

    2015-03-01

    While there is typically 100% survivability in birds challenged with vNDV under experimental conditions, either with vaccines formulated with a strain homologous or heterologous (different genotype) to the challenge virus, vaccine deficiencies are often noted in the field. We have developed an improved and more stringent protocol to experimentally evaluate live NDV vaccines, and showed for the first time under experimental conditions that a statistically significant reduction in mortality can be detected with genotype matched vaccines. Using both vaccine evaluation protocols (traditional and improved), birds were challenged with a vNDV of genotype XIII and the efficacy of live heterologous (genotype II) and homologous (genotype XIII) NDV vaccines was compared. Under traditional vaccination conditions there were no differences in survival upon challenge, but the homologous vaccine induced significantly higher levels of antibodies specific to the challenge virus. With the more stringent challenge system (multiple vaccine doses and early challenge with high titers of vNDV), the birds administered the homologous vaccine had superior humoral responses, reduced clinical signs, and reduced mortality levels than those vaccinated with the heterologous vaccine. These results provide basis for the implementation of more sensitive methods to evaluate vaccine efficacy.

  8. Vaccinomics Approach to Tick Vaccine Development.

    Science.gov (United States)

    Contreras, Marinela; Villar, Margarita; Alberdi, Pilar; de la Fuente, José

    2016-01-01

    Ticks are blood-feeding arthropod ectoparasites that transmit disease-causing pathogens to humans and animals worldwide. Vaccines using tick antigens have proven to be cost-effective and environmental friendly for the control of vector infestations and pathogen infection and transmission. However, new strategies are needed to identify tick protective antigens for development of improved vaccines. These strategies will be greatly enhanced by vaccinomics approaches starting from the study of tick-host-pathogen molecular interactions and ending in the characterization and validation of vaccine formulations. The discovery of tick antigens that affect both tick infestations and pathogen infection/transmission could be used for vaccines targeting human and animal populations at risk and reservoir species to reduce host exposure to ticks while reducing the number of infected ticks and their vector capacity for pathogens that affect human and animal health. In this chapter, we describe methods of the vaccinomics platform using transcriptomics and proteomics for the identification of candidate protective antigens in Ixodes scapularis, the vector for human and animal granulocytic anaplasmosis, tick-borne encephalitis, and Lyme disease.

  9. Fueling the engine and releasing the break:combinational therapy of cancer vaccines and immune checkpoint inhibitors

    Institute of Scientific and Technical Information of China (English)

    Jennifer Kleponis; Richard Skelton; Lei Zheng

    2015-01-01

    Immune checkpoint inhibitors are increasingly drawing much attention in the therapeutic development for cancer treatment. However, many cancer patients do not respond to treatments with immune checkpoint inhibitors, partly because of the lack of tumor-inifltrating effector T cells. Cancer vaccines may prime patients for treatments with immune checkpoint inhibitors by inducing effector T-cell infiltration into the tumors and immune checkpoint signals. The combination of cancer vaccine and an immune checkpoint inhibitor may function synergistically to induce more effective antitumor immune responses, and clinical trials to test the combination are currently ongoing.

  10. Dendritic cell-based vaccine for pancreatic cancer in Japan

    Institute of Scientific and Technical Information of China (English)

    Masato Okamoto; Masanori Kobayashi; Yoshikazu Yonemitsu; Shigeo Koido; Sadamu Homma

    2016-01-01

    "Vaccell" is a dendritic cell(DC)-based cancer vaccine which has been established in Japan. The DCs play central roles in deciding the direction of host immune reactions as well as antigen presentation. We have demonstrated that DCs treated with a streptococcal immune adjuvant OK-432, produce interleukin-12, induce Th1-dominant state, and elicit anti-tumor effects, more powerful than those treated with the known DCmaturating factors. We therefore decided to mature DCs by the OK-432 for making an effective DC vaccine, Vaccell. The 255 patients with inoperable pancreatic cancer who received standard chemotherapy combined with DC vaccines, were analyzed retrospectively. Survival time of the patients with positive delayed type hypersensitivity(DTH) skin reaction was significantly prolonged as compared with that of the patients with negative DTH. The findings strongly suggest that there may be "Responders" for the DC vaccine in advanced pancreatic cancer patients. We next conducted a smallscale prospective clinical study. In this trial, we pulsed HLA class Ⅱ-restricted WT1 peptide(WT1-Ⅱ) in addition to HLA class Ⅰ-restricted peptide(WT1-Ⅰ) into the DCs. Survival of the patients received WT1-Ⅰ and-Ⅱ pulsed DC vaccine was significantly extended as compared to that of the patients received DCs pulsed with WT1-Ⅰ or WT1-Ⅱ alone. Furthermore, WT1-specific DTH positive patients showed significantly improved the overall survival as well as progressionfree survival as compared to the DTH negative patients. The activation of antigen-specific immune responses by DC vaccine in combination with standard chemotherapy may be associated with a good clinical outcome in advanced pancreatic cancer. We are now planning a pivotal study of the Vaccell in appropriate protocols in Japan.

  11. Preparation of triple-negative breast cancer vaccine through electrofusion with day-3 dendritic cells.

    Directory of Open Access Journals (Sweden)

    Peng Zhang

    Full Text Available Dendritic cells (DCs are professional antigen-presenting cells (APCs in human immune system. DC-based tumor vaccine has met with some success in specific malignancies, inclusive of breast cancer. In this study, we electrofused MDA-MB-231 breast cancer cell line with day-3 DCs derived from peripheral blood monocytes, and explored the biological characteristics of fusion vaccine and its anti-tumor effects in vitro. Day-3 mature DCs were generated from day-2 immature DCs by adding cocktails composed of TNF-α, IL-1β, IL-6 and PEG2. Day-3 mature DCs were identified and electofused with breast cancer cells to generate fusion vaccine. Phenotype of fusion cells were identified by fluorescence microscope and flow cytometer. The fusion vaccine was evaluated for T cell proliferation, secretion of IL-12 and IFN-γ, and induction of tumor-specific CTL response. Despite differences in morphology, day-3 and day-7 DC expressed similar surface markers. The secretion of IL-12 and IFN-γ in fusion vaccine group was much higher than that in the control group. Compared with control group, DC-tumor fusion vaccine could better stimulate the proliferation of allogeneic T lymphocytes and kill more breast cancer cells (MDA-MB-231 in vitro. Day-3 DCs had the same function as the day-7 DCs, but with a shorter culture period. Our findings suggested that day-3 DCs fused with whole apoptotic breast cancer cells could elicit effective specific antitumor T cell responses in vitro and may be developed into a prospective candidate for adoptivet immunotherapy.

  12. 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 vaccination...... guidelines and policies for HPV vaccination. CONCLUSION: Current practices to prevent cervical cancer in the Pacific Region do not match the high burden of disease from cervical cancer. A regional approach, including reducing vaccine prices by bulk purchase of vaccine, technical support for implementation...

  13. [Research and development strategies, examples among new vaccines].

    Science.gov (United States)

    Denis, F; Ploy, M-C

    2009-05-01

    Classical methods are still providing new vaccines, but molecular biology and genetic engineering have enabled new approaches to development. Changes in vaccinology have involved the isolation, presentation and administration of vaccinal antigens or attenuated vaccinal strains. New methods of vaccine delivery other than injection will be used (e.g. mucosal administration) and new vectors or adjuvants will be added to vaccines in order to stimulate specific responses. New vaccines can also be obtained by using viral-like particles (VLP of papillomavirus), conjugate polysaccharides (N. meningitidis, S. pneumoniae) or the reassortment of segmented genomes (rotavirus, influenza). Here, we analyze the different steps of a vaccine's life using concrete cases of two new vaccines against papillomavirus and rotavirus. Vaccination has a promising future.

  14. Policy making for vaccine use as a driver of vaccine innovation and development in the developed world.

    Science.gov (United States)

    Seib, Katherine; Pollard, Andrew J; de Wals, Philippe; Andrews, Ross M; Zhou, Fangjun; Hatchett, Richard J; Pickering, Larry K; Orenstein, Walter A

    2017-03-07

    In the past 200years, vaccines have had unmistakable impacts on public health including declines in morbidity and mortality, most markedly in economically-developed countries. Highly engineered vaccines including vaccines for conditions other than infectious diseases are expected to dominate future vaccine development. We examine immunization vaccine policy as a driver of vaccine innovation and development. The pathways to recommendation for use of licensed vaccines in the US, UK, Canada and Australia have been similar, including: expert review of disease epidemiology, disease burden and severity; vaccine immunogenicity, efficacy and safety; programmatic feasibility; public demand; and increasingly cost-effectiveness. Other attributes particularly important in development of future vaccines are likely to include: duration of immunity for improved vaccines such as pertussis; a greater emphasis on optimizing community protection rather than direct protection only; programmatic implementation, feasibility, improvements (as in the case of development of a universal influenza vaccine); public concerns/confidence/fears related to outbreak pathogens like Ebola and Zika virus; and major societal burden for combating hard to treat diseases like HIV and antimicrobial resistant pathogens. Driving innovation and production of future vaccines faces enormous economic hurdles as available approaches, technologies and regulatory pathways become more complex. As such, cost-mitigating strategies and focused, aligned efforts (by governments, private organizations, and private-public partnerships) will likely be needed to continue to spur major advances in vaccine technologies and development.

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

    Directory of Open Access Journals (Sweden)

    Nubia Muñoz

    2009-11-01

    Full Text Available 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 vaccination of HPV-unexposed adolescents with screening using methods with higher sensitivity than cytology as HPV test may be more cost-effective than the strategies currently used. The cytology-based screening programs of Latin America countries including Colombia are very ineffective. The evidence in favor of the cost-effectiveness of other screening strategies such as HPV tests and visual inspection followed by immediate treatment for women with difficult access to health care services in developing countries warrants the immediate revision of the current strategies.

  16. New developments in the era of viral hepatitis vaccines

    OpenAIRE

    POYRAZ, Merve; Özdoğan, Osman Cavit

    2016-01-01

    Chronic hepatitis B and hepatitis C infections are major healthproblems in the world. Therefore, prevention of the transmission ofthe viral infections gets higher priority. Development of hepatitisB vaccines by recombinant technology provide higher preventionrates. However, this success could not be achieved with hepatitisC vaccine. The present review discusses recent developments forhepatitis B and C vaccines.Keywords: New vaccines, Hepatitis B, Hepatitis C

  17. Immune correlates for dengue vaccine development.

    Science.gov (United States)

    Srikiatkhachorn, Anon; Yoon, In-Kyu

    2016-01-01

    Dengue virus is the leading cause of vector-borne viral disease with four serotypes in circulation. Vaccine development has been complicated by the potential for both protection and disease enhancement during heterologous infection. Secondary infection triggers cross-reactive immune memory responses that have varying functional and epitope specificities that determine protection or risk. Strongly neutralizing antibodies to quaternary epitopes may be especially important for virus neutralization. Cell-mediated immunity dominated by Th1 functions may also play an important role. Determining an immune correlate of protection or risk would be highly beneficial for vaccine development but is hampered by mechanistic uncertainties and assay limitations. Clinical efficacy trials and human infection models along with a systems approach may provide future opportunities to elucidate such correlates.

  18. 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...... 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...... 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...

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

    Directory of Open Access Journals (Sweden)

    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

  20. Messenger RNA vaccine based on recombinant MS2 virus-like particles against prostate cancer.

    Science.gov (United States)

    Li, Jinming; Sun, Yanli; Jia, Tingting; Zhang, Rui; Zhang, Kuo; Wang, Lunan

    2014-04-01

    Prostate cancer (PCa) is the most diagnosed cancer in the western male population with high mortality. Recently, alternative approaches based on immunotherapy including mRNA vaccines for PCa have shown therapeutic promise. However, for mRNA vaccine, several disadvantages such as the instability of mRNA, the high cost of gold particles, the limited production scale for mRNA-transfected dendritic cells in vitro, limit their development. Herein, recombinant bacteriophage MS2 virus-like particles (VLPs), which based on the interaction of a 19-nucleotide RNA aptamer and the coat protein of bacteriophage MS2, successfully addressed these questions, in which target mRNA was packaged by MS2 capsid. MS2 VLP-based mRNA vaccines were easily prepared by recombinant protein technology, nontoxic and RNase-resistant. We show the packaged mRNA was translated into protein as early as 12 hr after phagocytosed by macrophages. Moreover, MS2 VLP-based mRNA vaccines induced strong humoral and cellular immune responses, especially antigen-specific cytotoxic T-lymphocyte (CTL) and balanced Th1/Th2 responses without upregulation of CD4(+) regulatory T cells, and protected C57BL/6 mice against PCa completely. As a therapeutic vaccine, MS2 VLP-based mRNA vaccines delayed tumor growth. Our results provide proof of concept on the efficacy and safety of MS2 VLP-based mRNA vaccine, which provides a new delivery approach for mRNA vaccine and implies important clinical value for the prevention and therapy of PCa.

  1. Global Efforts in the Development of Vaccines for Tuberculosis: Requirements for Improved Vaccines Against Mycobacterium tuberculosis.

    Science.gov (United States)

    Méndez-Samperio, P

    2016-10-01

    Currently, more than 9.0 million people develop acute pulmonary tuberculosis (TB) each year and about 1.5 million people worldwide die from this infection. Thus, developing vaccines to prevent active TB disease remains a priority. This article discusses recent progress in the development of new vaccines against TB and focusses on the main requirements for development of improved vaccines against Mycobacterium tuberculosis (M. tb). Over the last two decades, significant progress has been made in TB vaccine development, and some TB vaccine candidates have currently completed a phase III clinical trial. The potential public health benefits of these vaccines are possible, but it will need much more effort, including new global governance investment on this research. This investment would certainly be less than the annual global financial toll of TB treatment.

  2. Progress toward the development of universal influenza vaccines.

    Science.gov (United States)

    Hoft, Daniel F; Belshe, Robert B

    2014-01-01

    Influenza remains a major problem causing significant morbidity and mortality annually and periodic pandemics with the potential for 10-100 fold increased mortality. Conventional vaccines can be highly effective if generated each year to match currently circulating viruses. Ongoing research focuses on producing cross-protective vaccines that induce T cell and/ or antibody responses specific for highly conserved viral epitopes. The Saint Louis University Center for Vaccine Development (SLUCVD) is highly engaged in multiple efforts to generate universally relevant influenza vaccines.

  3. Response to influenza virus vaccination during chemotherapy in patients with breast cancer

    NARCIS (Netherlands)

    Meerveld-Eggink, A.; de Weerdt, O.; van der Velden, A. M. T.; Los, M.; van der Velden, A. W. G.; Stouthard, J. M. L.; Nijziel, M. R.; Westerman, M.; Beeker, A.; van Beek, R.; Rimmelzwaan, G. F.; Rijkers, G. T.; Biesma, D. H.

    2011-01-01

    Background: Patients receiving chemotherapy are at increased risk for influenza virus infection. Little is known about the preferred moment of vaccination during chemotherapy. Patients and methods: Breast cancer patients received influenza vaccination during FEC (5-fluorouracil, epirubicin and cyclo

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

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

    2016-06-03

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

  6. Dengue vaccines: Challenges, development, current status and prospects

    Directory of Open Access Journals (Sweden)

    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.

  7. Dengue vaccines: challenges, development, current status and prospects.

    Science.gov (United States)

    Ghosh, A; Dar, L

    2015-01-01

    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.

  8. Newcastle Disease Virus as a Vaccine Vector for Development of Human and Veterinary Vaccines.

    Science.gov (United States)

    Kim, Shin-Hee; Samal, Siba K

    2016-07-04

    Viral vaccine vectors have shown to be effective in inducing a robust immune response against the vaccine antigen. Newcastle disease virus (NDV), an avian paramyxovirus, is a promising vaccine vector against human and veterinary pathogens. Avirulent NDV strains LaSota and B1 have long track records of safety and efficacy. Therefore, use of these strains as vaccine vectors is highly safe in avian and non-avian species. NDV replicates efficiently in the respiratory track of the host and induces strong local and systemic immune responses against the foreign antigen. As a vaccine vector, NDV can accommodate foreign sequences with a good degree of stability and as a RNA virus, there is limited possibility for recombination with host cell DNA. Using NDV as a vaccine vector in humans offers several advantages over other viral vaccine vectors. NDV is safe in humans due to host range restriction and there is no pre-existing antibody to NDV in the human population. NDV is antigenically distinct from common human pathogens. NDV replicates to high titer in a cell line acceptable for human vaccine development. Therefore, NDV is an attractive vaccine vector for human pathogens for which vaccines are currently not available. NDV is also an attractive vaccine vector for animal pathogens.

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

    Science.gov (United States)

    Liu, Jun

    2009-04-01

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

  10. Research progress in live attenuated Brucella vaccine development.

    Science.gov (United States)

    Wang, Zhen; Wu, Qingmin

    2013-01-01

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

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

    Science.gov (United States)

    Volz, A; Sutter, G

    2017-01-01

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

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

    OpenAIRE

    Samantha Sayers; Guerlain Ulysse; Zuoshuang Xiang; Yongqun He

    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. Bi...

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

    Energy Technology Data Exchange (ETDEWEB)

    Wieërs, Grégoire; Demotte, Nathalie; Godelaine, Danièle; Bruggen, Pierre van der, E-mail: pierre.vanderbruggen@bru.licr.org [Ludwig Institute for Cancer Research and Université catholique de Louvain, de Duve Institute, 74 av. Hippocrate, P.O. Box B1-7403, B-1200 Brussels (Belgium)

    2011-07-18

    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.

  14. OBSERVATION ON VACCINATING Newcastle Disease Virus Vaccine with Inhalation and Preventing Recurrence of Nasopharyngeal cancer after Radiotherapy

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective: To understand whether the Newcastle disease virus(NDV) vaccine can successfully vaccinate the rabbits and volunteers of cancer patients by inhalation and to observe the effects of NDV vaccine on nasopharyngeal carcinoma (NRC) patients after radiotherapy. Methods: The live NDV vaccine was vaccinated through nasal cavities of rabbits, NPC patients and other cancer patients who were treated by surgery or chemotherapy with larynx spray. The blood specimens of vein from the tested rabbits and volunteers of patients with cancer were collected before and after vaccination. The anti-NDV-antibody in serum was detected by conventional blood coagulation inhibiting method. The white blood cell (WBC) amount in blood samples was counted. In addition, the NPC patients after radiotherapy were divided into both test group and control group with random match. The both were followed-up by multiple kinds of way in order to understand effects of NDV immunotherapy for NPC. Results: The anti-NDV-antibody level of the rabbits and the patients with NPC rose significantly after vaccination. The WBC amount of cancer patients treated by surgery or chemotherapy also rose significantly after vaccination. The recurrence rate (3.23%) of NRC patients in test group who received immunotherapy of NDV vaccine for 4 to 10 treatment courses within 3 years after end of radiotherapy were significantly lower than that (25.81%) of the control group (P<0.025). Conclusion: The NDV vaccine La Sota strain can vaccinate the rabbits and the cancer patients in success by inhalation. And it has remarkable effect to decrease 3 year recurrence rate of NRC patients after radiotherapy.

  15. Measuring vaccine hesitancy: The development of a survey tool.

    Science.gov (United States)

    Larson, Heidi J; Jarrett, Caitlin; Schulz, William S; Chaudhuri, Mohuya; Zhou, Yuqing; Dube, Eve; Schuster, Melanie; MacDonald, Noni E; Wilson, Rose

    2015-08-14

    In March 2012, the SAGE Working Group on Vaccine Hesitancy was convened to define the term "vaccine hesitancy", as well as to map the determinants of vaccine hesitancy and develop tools to measure and address the nature and scale of hesitancy in settings where it is becoming more evident. The definition of vaccine hesitancy and a matrix of determinants guided the development of a survey tool to assess the nature and scale of hesitancy issues. Additionally, vaccine hesitancy questions were piloted in the annual WHO-UNICEF joint reporting form, completed by National Immunization Managers globally. The objective of characterizing the nature and scale of vaccine hesitancy issues is to better inform the development of appropriate strategies and policies to address the concerns expressed, and to sustain confidence in vaccination. The Working Group developed a matrix of the determinants of vaccine hesitancy informed by a systematic review of peer reviewed and grey literature, and by the expertise of the working group. The matrix mapped the key factors influencing the decision to accept, delay or reject some or all vaccines under three categories: contextual, individual and group, and vaccine-specific. These categories framed the menu of survey questions presented in this paper to help diagnose and address vaccine hesitancy.

  16. 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.

  17. Therapeutic vaccines in non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Socola F

    2013-09-01

    Full Text Available Francisco Socola,1 Naomi Scherfenberg,2 Luis E Raez3 1Division of Hematology/Oncology, Sylvester Comprehensive Cancer Center, University of Miami Leonard M Miller School of Medicine, Miami, Florida, USA; 2University of Miami Leonard M Miller School of Medicine, Miami, Florida, USA; 3Thoracic Oncology Program, Memorial Cancer Institute, Memorial Health Care System, Pembroke Pines, Florida, USA Abstract: Non-small cell lung cancer (NSCLC unfortunately carries a very poor prognosis. Patients usually do not become symptomatic, and therefore do not seek treatment, until the cancer is advanced and it is too late to employ curative treatment options. New therapeutic options are urgently needed for NSCLC, because even current targeted therapies cure very few patients. Active immunotherapy is an option that is gaining more attention. A delicate and complex interplay exists between the tumor and the immune system. Solid tumors utilize a variety of mechanisms to evade immune detection. However, if the immune system can be stimulated to recognize the tumor as foreign, tumor cells can be specifically eliminated with little systemic toxicity. A number of vaccines designed to boost immunity against NSCLC are currently undergoing investigation in phase III clinical trials. Belagenpumatucel-L, an allogeneic cell vaccine that decreases transforming growth factor (TGF-β in the tumor microenvironment, releases the immune suppression caused by the tumor and it has shown efficacy in a wide array of patients with advanced NSCLC. Melanoma-associated antigen A3 (MAGE-A3, an antigen-based vaccine, has shown promising results in MAGE-A3+ NSCLC patients who have undergone complete surgical resection. L-BLP25 and TG4010 are both antigenic vaccines that target the Mucin 1 protein (MUC-1, a proto-oncogene that is commonly mutated in solid tumors. CIMAVax is a recombinant human epidermal growth factor (EGF vaccine that induces anti-EGF antibody production and prevents EGF

  18. Anti-Lyme Subunit Vaccines: Design and Development of Peptide-Based Vaccine Candidates.

    Science.gov (United States)

    Small, Christina M; Mwangi, Waithaka; Esteve-Gassent, Maria D

    2016-01-01

    Vaccinology today has been presented with several avenues to improve protection against infectious disease. The recent employment of the reverse vaccinology technique has changed the face of vaccine development against many pathogens, including Borrelia burgdorferi, the causative agent of Lyme disease. Using this technique, genomics and in silico analyses come together to identify potentially antigenic epitopes in a high-throughput fashion. The forward methodology of vaccine development was used previously to generate the only licensed human vaccine for Lyme disease, which is no longer on the market. Using reverse vaccinology to identify new antigens and isolate specific epitopes to protect against B. burgdorferi, subunit vaccines will be generated that lack reactogenic and nonspecific epitopes, yielding more effective vaccine candidates. Additionally, novel epitopes are being utilized and are presently in the commercialization pipeline both for B. burgdorferi and other spirochaetal pathogens. The versatility and methodology of the subunit protein vaccine are described as it pertains to Lyme disease from conception to performance evaluation.

  19. The blueprint for vaccine research & development: walking the path for better TB vaccines.

    Science.gov (United States)

    Lienhardt, Christian; Fruth, Uli; Greco, Michel

    2012-03-01

    Much progress has been made in TB vaccine research over the past ten years, and a series of new live genetically altered mycobacterial vaccines, viral-vectored vaccines and sub-unit vaccines composed of recombinant antigens are presently in clinical development phases. A series of challenges remain, however, to be addressed in order to develop new and better candidate TB vaccines, especially an expansion of our knowledge of what constitutes protective immunity in TB, the identification of the most suitable vaccination strategies, the capacity and infrastructure to conduct large-scale trials in endemic countries, the investment in vaccine manufacturing capacity, and the development of effective regulatory pathways that shorten review timelines. In this brief paper, we review how the Vaccine Blueprint places itself in the continuation and expansion of two groundbreaking initiatives taking place over the last two years, that is, an invigorated Global Plan to Stop TB 2011-2015 that gives a clear emphasis on Research and Development, and the International Roadmap for TB Research, that identifies key priorities for research on TB vaccines, spanning from the most fundamental research aspects to the more field-based epidemiological aspects.

  20. TPD52: A Novel Vaccine Target for Prostate Cancer

    Science.gov (United States)

    2009-09-01

    Cancer Res 1996;2:1255–61. 51. Bright RK, Vocke CD, Emmert- Buck MR, et al. Generation and genetic characterization of immortal human prostate epithelial...total of 2 injections given at 14 day intervals followed by a booster immunization given 35 days after the second immunization. Empty vector DNA...TCCATGACGTTCCTGA CGTT) [25]. The protein vaccines were administered as an alum precipitate and a booster of the same dose was given approximately 2 weeks

  1. 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.

  2. 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.

  3. Selection and characterization of vaccine strain for Enterovirus 71 vaccine development.

    Science.gov (United States)

    Chang, Jui-Yuan; Chang, Cheng-Peng; Tsai, Hutchinson Hau-Pong; Lee, Chen-Dou; Lian, Wei-Cheng; Ih-Jen-Su; Sai, I-Hsi; Liu, Chia-Chyi; Chou, Ai-Hsiang; Lu, Ya-Jung; Chen, Ching-Yao; Lee, Pi-Hsiu; Chiang, Jen-Ron; Chong, Pele Choi-Sing

    2012-01-17

    Enterovirus 71 (EV71) has recently emerged as an important neurotropic virus in Asia because effective medications and prophylactic vaccine against EV71 infection are not available. Based on the success of inactivated poliovirus vaccine, the Vero cell-based chemically inactivated EV71 vaccine candidate could be developed. Identification of EV71 vaccine strain which can grow to high titer in Vero cell and induce cross-genotype virus neutralizing antibody responses represents the first step in vaccine development. In this report we describe the characterization and validation of a clinical isolate E59 belonging to B4 sub-genotype based on VP1 genetic analysis. Before selected as the vaccine strain, the genetic stability of E59 in passage had been analyzed based on the nucleotide sequences obtained from the Master Virus Seed, Working Seed banks and the virus harvested from the production lots, and found to be identical to those found in the original isolate. These results indicate that E59 vaccine strain has strong genetic stability in passage. Using this vaccine strain the prototype EV71 vaccine candidate was produced from 20L of Vero cell grown in serum-containing medium. The production processes were investigated, characterized and quantified to establish the potential vaccine manufacturing process including the time for virus harvest, the membrane for diafiltration and concentration, the gel-filtration chromatography for the down-stream virus purification, and the methods for viral inactivation. Finally, the inactivated virion vaccine candidate containing sub-microgram of viral proteins formulated with alum adjuvant was found to induce strong virus neutralizing antibody responses in mice and rabbits. Therefore, these results provide valuable information for cell-based EV71 vaccine development.

  4. Vaccines against human papillomavirus infections: protection against cancer, genital warts or both?

    Science.gov (United States)

    Joura, E A; Pils, S

    2016-12-01

    Since 2006, three vaccines against infections and disease caused by human papillomavirus (HPV) became available in Europe-in 2006 a quadrivalent HPV 6/11/16/18 vaccine, in 2007 a bivalent HPV 16/18 vaccine and in 2015 a nonavalent HPV 6/11/16/18/31/33/45/52/58 vaccine. HPV 16 and 18 are the most oncogenic HPV strains, causing about 70% of cervical and other HPV-related cancers, HPV 6 and 11 cause 85% of all genital warts. The additional types of the polyvalent vaccine account for about 20% of invasive cervical cancer and >35% of pre-cancer. The potential differences between these vaccines caused some debate. All three vaccines give a robust and long-lasting protection against the strains in the various vaccines. The promise of cross-protection against other types (i.e. HPV 31/33/45) and hence a broader cancer protection was not fulfilled because these observations were confounded by the vaccine efficacy against the vaccine types. Furthermore, cross-protection was not consistent over various studies, not durable and not consistently seen in the real world experience. The protection against disease caused by oncogenic HPV strains was not compromised by the protection against low-risk types causing genital warts. The most effective cancer protection to date can be expected by the nonavalent vaccine, data indicate a 97% efficacy against cervical and vulvovaginal pre-cancer caused by these nine HPV types.

  5. Cancer Vaccine:promise in the 21st Century%癌症疫苗:21世纪征服癌症的希望

    Institute of Scientific and Technical Information of China (English)

    曾钢

    2001-01-01

    Cancer vaccine,the idea of utilizing the immune system to prevent and/or treat human cancers has been proposed for nearly a century.Only since the last decasde,the discovery of tumor-associated antigens has helped us to understand the molecular details of tumor-immune system interaction as well as provided new opportunities for cancer vaccine development.Cancer vaccine has seen remarked progress in both basic scientific research and clinical trials based on the discoveries of these studies.Inaddition,more and more efforts from industry are being made to the commercialization of these discoverise.Cancer vaccine,in combination with surgery,chemotherapy and rediation therapy may potentially provide effective treatment to most human cancers in the 21st century.

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

    Directory of Open Access Journals (Sweden)

    Morgado MG

    2002-01-01

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

  7. Developing Countries Vaccine Manufacturers Network: doing good by making high-quality vaccines affordable for all.

    Science.gov (United States)

    Pagliusi, Sonia; Leite, Luciana C C; Datla, Mahima; Makhoana, Morena; Gao, Yongzhong; Suhardono, Mahendra; Jadhav, Suresh; Harshavardhan, Gutla V J A; Homma, Akira

    2013-04-18

    The Developing Countries Vaccine Manufacturers Network (DCVMN) is a unique model of a public and private international alliance. It assembles governmental and private organizations to work toward a common goal of manufacturing and supplying high-quality vaccines at affordable prices to protect people around the world from known and emerging infectious diseases. Together, this group of manufacturers has decades of experience in manufacturing vaccines, with technologies, know-how, and capacity to produce more than 40 vaccines types. These manufacturers have already contributed more than 30 vaccines in various presentations that have been prequalified by the World Health Organization for use by global immunization programmes. Furthermore, more than 45 vaccines are in the pipeline. Recent areas of focus include vaccines to protect against rotavirus, human papillomavirus (HPV), Japanese encephalitis, meningitis, hepatitis E, poliovirus, influenza, and pertussis, as well as combined pentavalent vaccines for children. The network has a growing number of manufacturers that produce a growing number of products to supply the growing demand for vaccines in developing countries.

  8. Vaccine development and deployment: opportunities and challenges in India.

    Science.gov (United States)

    Gupta, Sanjukta Sen; Nair, G Balakrish; Arora, Narendra Kumar; Ganguly, Nirmal Kumar

    2013-04-18

    The Indian economy is among the fastest growing economies in the world. The country forayed into manufacturing vaccines starting with a few public-sector manufacturers in the late 1960s but has emerged as the major supplier of basic Expanded Programme on Immunization vaccines to the United Nations Children's Fund (UNICEF) because of substantial private-sector investment in the area. The Indian vaccine industry is now able to produce new and more complex vaccines such as the meningitis, Haemophilus influenzae type b, and pneumococcal conjugate vaccines, rotavirus vaccine and influenza A (H1N1) vaccines. This has been possible because of an attractive investment environment, effective and innovative governmental support, international partnerships and the growing in-country technical work force. A large number of vaccines, including those mentioned, is available and administered in the private sector within the country, but India has been slow in introducing new vaccines in its publically funded programs. Growth in the economy and technological accomplishments are not reflected in a reduction in health inequalities, and India continues to contribute significantly to global child mortality figures. This paper reviews the development of the Indian vaccine industry, policy support for it and its current status. It also highlights opportunities and challenges for the introduction of new and underutilized vaccines at home.

  9. Adjuvants for peptide-based cancer vaccines

    OpenAIRE

    Khong, Hiep; Overwijk, Willem W

    2016-01-01

    Cancer therapies based on T cells have shown impressive clinical benefit. In particular, immune checkpoint blockade therapies with anti-CTLA-4 and anti-PD-1/PD-L1 are causing dramatic tumor shrinkage and prolonged patient survival in a variety of cancers. However, many patients do not benefit, possibly due to insufficient spontaneous T cell reactivity against their tumors and/or lacking immune cell infiltration to tumor site. Such tumor-specific T cell responses could be induced through anti-...

  10. 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.

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

    OpenAIRE

    Iole Macchia; Francesca Urbani; Enrico Proietti

    2013-01-01

    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 cytometr...

  12. Design of nanomaterial based systems for novel vaccine development.

    Science.gov (United States)

    Yang, Liu; Li, Wen; Kirberger, Michael; Liao, Wenzhen; Ren, Jiaoyan

    2016-05-26

    With lower cell toxicity and higher specificity, novel vaccines have been greatly developed and applied to emerging infectious and chronic diseases. However, due to problems associated with low immunogenicity and complicated processing steps, the development of novel vaccines has been limited. With the rapid development of bio-technologies and material sciences, nanomaterials are playing essential roles in novel vaccine design. Incorporation of nanomaterials is expected to improve delivery efficiency, to increase immunogenicity, and to reduce the administration dosage. The purpose of this review is to discuss the employment of nanomaterials, including polymeric nanoparticles, liposomes, virus-like particles, peptide amphiphiles micelles, peptide nanofibers and microneedle arrays, in vaccine design. Compared to traditional methods, vaccines made from nanomaterials display many appealing benefits, including precise stimulation of immune responses, effective targeting to certain tissue or cells, and desirable biocompatibility. Current research suggests that nanomaterials may improve our approach to the design and delivery of novel vaccines.

  13. 肺癌免疫逃逸机制与肺癌疫苗%The Immune Escape Mechanisms of Lung Cancer and Lung Cancer Vaccine

    Institute of Scientific and Technical Information of China (English)

    李自青; 刘宏

    2011-01-01

    Abstract: Lung cancer is a kind of disease which is seriously imperiling human health and life. The main pathogenesis of lung cancer is the occurrence of immune escape of cancer cell, which by changing surface antigens, abnormally expressing MHC-I molecules and the costimulatory molecules, highly expressing the FasL and dendritic cell function defects. Lung cancer vaccine is biological agents designed for antagonizing immune escape mechanisms of lung cancer. At present, lung cancer vaccines being developed are mainly composed of synthetic peptide vaccine, dendritic cell vaccines, genetically modified vaccines and nucleic acid vaccine, et al. Clinical trials have shown that these vaccines can stimulate active immune response for lung cancer-specific antigens, but the clinical efficacy remains to be further observed.%肺癌是严重威胁人类健康和生命的疾病.肺癌的主要发病机制是癌细胞通过表面抗原的改变、MHC-I分子和共刺激分子表达异常、树突状细胞功能缺陷以及肺癌细胞高表达FasL等机制实现了免疫逃逸.肺癌疫苗是针对肺癌免疫逃逸机制而设计的生物制剂.目前正在研制的肺癌疫苗主要有合成肽疫苗、树突状细胞疫苗、转基因疫苗和核酸疫苗等几类.临床试验表明,这些疫苗能激发针对肺癌特异性抗原的主动免疫反应,但临床效果仍有待进一步的观察.

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

    Directory of Open Access Journals (Sweden)

    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.

  15. 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.

  16. Human Papillomavirus Vaccine as an Anticancer Vaccine: Collaborative Efforts to Promote Human Papillomavirus Vaccine in the National Comprehensive Cancer Control Program.

    Science.gov (United States)

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

    2017-03-06

    Widespread use of the human papillomavirus (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) National Comprehensive Cancer Control Program (NCCCP) awardees are well positioned to work with immunization programs to increase vaccine uptake. The CDC chronic disease management information system was queried for objectives and activities associated with HPV vaccine that were reported by NCCCP awardees from 2013 to 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. 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. 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 healthcare community.

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

    Science.gov (United States)

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

    2013-11-01

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

  18. Is HCMV vaccine an unmet need? The state of art of vaccine development.

    Science.gov (United States)

    Chiurchiu, S; Calo Carducci, F I; Rocchi, F; Simonetti, A; Bonatti, G; Salmaso, S; Melchiorri, D; Pani, L; Rossi, P

    2013-01-01

    Congenital HCMV infection is the most frequent congenital infection, with an incidence of 0.2- 2.5 percent among all live births. About 11 percent of infected newborns show symptoms at birth, including hepato-splenomegaly, thrombocytopenia, neurologic involvement, hearing impairment and visual deficit. Moreover, 5-25 percent of the asymptomatic congenital HCMV-infected neonates will develop sequelae over months or even years. The relevant social burden, the economic costs of pre-natal screening, post-natal diagnosis, follow-up and possible therapy, although still limited, are the major factors to be considered. Several types of vaccines have been explored in order to develop an effective and safe HCMV vaccine: live attenuated, subunit, vectored, peptide, DNA, and subviral ones, but none are available for use. This review illustrates the different vaccine types studied to date, focusing on the possible vaccination strategy to be implemented once the HCMV vaccine is available, in terms of target population.

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

    Science.gov (United States)

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

    2016-01-01

    Background 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. Objective To determine knowledge, awareness and attitude of college students on HPV, HPV vaccine and cervical cancer. Method 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. Results Out of a total of 1580 students, girls had more knowledge about cervical cancer (82.45%, p<0.001), HPV (45.61%, p<0.001) and HPV vaccines (44%, p<0.001) when compared to those in boys. However, knowledge about the types of HPV and vaccines was poor. Interestingly, students from biology-major had more knowledge and awareness about cervical cancer (81.89%, p<0.001) and HPV (46.58%, <0.001) when compared to non-biology students. Girls from both biology and non-biology group had higher awareness compared to boys. Analysis of odds ratio (ORs) along with 95% CI showed older girls with 1.2 to 3 fold (p<0.05) higher knowledge than boys. All students agreed that girls should get vaccinated against HPV (p<0.001). Conclusion It is suggested that there is a need for educational intervention and awareness campaigns to augment HPV immunization program for control of cervical cancer in India. PMID:27861611

  20. A cancer vaccine induces expansion of NY-ESO-1-specific regulatory T cells in patients with advanced melanoma.

    Science.gov (United States)

    Ebert, Lisa M; MacRaild, Sarah E; Zanker, Damien; Davis, Ian D; Cebon, Jonathan; Chen, Weisan

    2012-01-01

    Cancer vaccines are designed to expand tumor antigen-specific T cells with effector function. However, they may also inadvertently expand regulatory T cells (Treg), which could seriously hamper clinical efficacy. To address this possibility, we developed a novel assay to detect antigen-specific Treg based on down-regulation of surface CD3 following TCR engagement, and used this approach to screen for Treg specific to the NY-ESO-1 tumor antigen in melanoma patients treated with the NY-ESO-1/ISCOMATRIX™ cancer vaccine. All patients tested had Treg (CD25(bright) FoxP3(+) CD127(neg)) specific for at least one NY-ESO-1 epitope in the blood. Strikingly, comparison with pre-treatment samples revealed that many of these responses were induced or boosted by vaccination. The most frequently detected response was toward the HLA-DP4-restricted NY-ESO-1(157-170) epitope, which is also recognized by effector T cells. Notably, functional Treg specific for an HLA-DR-restricted epitope within the NY-ESO-1(115-132) peptide were also identified at high frequency in tumor tissue, suggesting that NY-ESO-1-specific Treg may suppress local anti-tumor immune responses. Together, our data provide compelling evidence for the ability of a cancer vaccine to expand tumor antigen-specific Treg in the setting of advanced cancer, a finding which should be given serious consideration in the design of future cancer vaccine clinical trials.

  1. Issues and challenges in implementing cervical cancer screenings in the emergence of HPV vaccination in Thailand.

    Science.gov (United States)

    Juntasopeepun, Phanida; Davidson, Patricia M; Srisomboon, Jatupol

    2012-01-01

    The discovery of the HPV vaccine has been a major breakthrough in preventing cervical cancer and other HPV-related diseases around the globe. Cervical cancer is a significant public health problem in Thailand. Despite the long-time availability of cervical cancer screening programs in Thailand, the uptake among the target female population remains low. HPV vaccines were approved by the Food and Drug Administration of Thailand in 2007. As of March 2011, due to financial limitations, HPV vaccines have still not been included in the national immunization program under the public health benefit plans although individuals has the option to pay privately for the vaccine. This paper discusses the issues and challenges in implementing cervical cancer screening programs in the era of HPV vaccination in Thailand. Recommendations to increase the uptake of cervical cancer screening and further research to inform a policy regarding the cervical cancer screening measures are proposed.

  2. Combination recombinant simian or chimpanzee adenoviral vectors for vaccine development.

    Science.gov (United States)

    Cheng, Cheng; Wang, Lingshu; Ko, Sung-Youl; Kong, Wing-Pui; Schmidt, Stephen D; Gall, Jason G D; Colloca, Stefano; Seder, Robert A; Mascola, John R; Nabel, Gary J

    2015-12-16

    Recombinant adenoviral vector (rAd)-based vaccines are currently being developed for several infectious diseases and cancer therapy, but pre-existing seroprevalence to such vectors may prevent their use in broad human populations. In this study, we investigated the potential of low seroprevalence non-human primate rAd vectors to stimulate cellular and humoral responses using HIV/SIV Env glycoprotein (gp) as the representative antigen. Mice were immunized with novel simian or chimpanzee rAd (rSAV or rChAd) vectors encoding HIV gp or SIV gp by single immunization or in heterologous prime/boost combinations (DNA/rAd; rAd/rAd; rAd/NYVAC or rAd/rLCM), and adaptive immunity was assessed. Among the rSAV and rChAd tested, rSAV16 or rChAd3 vector alone generated the most potent immune responses. The DNA/rSAV regimen also generated immune responses similar to the DNA/rAd5 regimen. rChAd63/rChAd3 and rChAd3 /NYVAC induced similar or even higher levels of CD4+ and CD8+ T-cell and IgG responses as compared to rAd28/rAd5, one of the most potent combinations of human rAds. The optimized vaccine regimen stimulated improved cellular immune responses and neutralizing antibodies against HIV compared to the DNA/rAd5 regimen. Based on these results, this type of novel rAd vector and its prime/boost combination regimens represent promising candidates for vaccine development.

  3. Recombinant cancer vaccines and new vaccine targets. Interview by Jenaid Rees.

    Science.gov (United States)

    Schlom, Jeffrey

    2013-10-01

    Interview by Jenaid Rees, Commissioning Editor Jeffrey Schlom obtained his PhD from Rutgers University (NJ, USA). After obtaining his PhD, he worked at Columbia University (NY, USA) before moving in 1973 to the National Cancer Institute, National Institutes of Health (MD, USA). Since then he has served as the Chief of several sections, including his present position as the Chief of the Laboratory of Tumor Immunology and Biology in the Center for Cancer Research which he has held for the past 30 years. During this period, he has worked as an Adjunct Professor at George Washington University (Washington, DC, USA), served on the Editorial Board of several journals and holds membership in a number of committees. He holds over 30 patents and patent applications in the areas of vaccines, tumor antigens and monoclonal antibodies and has received honors and awards throughout his career. Jeffrey Schlom has been involved in translational research involving the immunotherapy of a range of carcinomas and predominantly works in the areas of tumor immunology, mechanisms of tumor cell-immune cell interactions and immune mechanisms. He has recently been working on the design and characterization of recombinant vaccines for cancer therapy.

  4. Respiratory Homeostasis and Exploitation of the Immune System for Lung Cancer Vaccines.

    Science.gov (United States)

    Yagui-Beltrán, Adam; Coussens, Lisa M; Jablons, David M

    2009-01-01

    Lung cancer is the leading cause of all cancer deaths in the US. The international scientific and clinical community has made significant advances toward understanding specific molecular mechanisms underlying lung carcinogenesis; however, despite these insights and advances in surgery and chemoradiotherapy, the prognosis for non-small-cell lung cancer (NSCLC) remains poor. Nonetheless, significant effort is being focused on advancing translational research evaluating the efficacy of novel targeted therapeutic strategies for lung cancer. Illustrative examples of this include antagonists of the epidermal growth factor receptor (EGFR), tyrosine kinase inhibitors (TKIs) such as gefitinib and erlotinib, and a diverse assortment of anti-angiogenic compounds targeting growth factors and/or their receptors that regulate tumor-associated angiogenic programs. In addition, with the increased awareness of the significant role chronically activated leukocytes play as potentiators of solid-tumor development, the role of innate and adaptive immune cells as regulators of lung carcinogenesis is being examined. While some of these studies are examining how novel therapeutic strategies may enhance the efficacy of lung cancer vaccines, others are evaluating the intrinsic characteristics of the immune response to lung cancer in order to identify rate-limiting molecular and/or cellular programs to target with novel anticancer therapeutics. In this article, we explore important aspects of the immune system and its role in regulating normal respiratory homeostasis compared with the immune response accompanying development of lung cancer. These hallmarks are then discussed in the context of recent efforts to develop lung cancer vaccines, where we have highlighted important concepts that must be taken into consideration for future development of novel therapeutic strategies and clinical trials assessing their efficacy.

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

    Science.gov (United States)

    Medici, Natasha P; Del Poeta, Maurizio

    2015-12-01

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

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

    Directory of Open Access Journals (Sweden)

    Natasha P Medici

    2015-01-01

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

  7. 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.

  8. Expression profile of saccharide epitope CaMBr1 in normal and neoplastic tissue from dogs, cats, and rats: implication for the development of human-derived cancer vaccines.

    Science.gov (United States)

    Adobati, E; Zacchetti, A; Perico, M E; Cremonesi, F; Rasi, G; Vallebona, P S; Hagenaars, M; Kuppen, P J; Pastan, I; Panza, L; Russo, G; Colnaghi, M I; Canevari, S

    1999-11-01

    CaMBr1 is a blood group-related tumour-associated antigen, whose pattern of expression provides a therapeutic window for passive or active immunotherapy and points to the promise of a vaccine against carcinomas overexpressing this antigen. In this context, an animal model that closely mimics the human situation would be extremely useful. We, therefore, utilised the murine monoclonal antibody MBr1, which defines CaMBr1, as a useful probe to detect the molecule targeted for vaccine development on canine and feline spontaneous breast and uterus tumours and on their normal counterparts, and on rat normal tissues and carcinoma cell lines. Immunoperoxidase staining of cryostat sections revealed homogeneous CaMBr1 expression only in normal feline uterus and a uterus papilloma, whereas MBr1 reactivity was very weak and heterogeneous in normal (1/3 and 1/3) and tumour (1/10 and 1/6) breast tissues from dogs and cats, respectively. In contrast, the data obtained in rat tissues were reproducible in the strains tested and showed that CaMBr1 was expressed in all epithelial tissues of the digestive tract, although with variable intensities. Monoclonal antibody staining appeared to correspond to membrane-bound structures as well as mucinous secretions. Similarly, secretion products of lactating mammary glands expressed CaMBr1. The spectrum of expression on rat digestive tract was broader than that in humans but the specificity of MBr1 reactivity was confirmed by competition assay with a synthetic tetrasaccharide that mimics the CaMBr1 antigen. On FACS analysis, only one of two clonal derivatives of the rat breast carcinoma line RAMA 25 expressed CaMBr1, and a negative cell subset was evident in repeated experiments. By contrast, both colon carcinoma lines, DHD/K12 and CC531, showed staining with MBr1, albeit at different levels of intensity, and no evidence of a negative subset. The cell line CC531 maintained or even increased CaMBr1 expression levels following transplantation in

  9. Beyond empiricism: informing vaccine development through innate immunity research.

    Science.gov (United States)

    Levitz, Stuart M; Golenbock, Douglas T

    2012-03-16

    Although a great public heath success, vaccines provide suboptimal protection in some patient populations and are not available to protect against many infectious diseases. Insights from innate immunity research have led to a better understanding of how existing vaccines work and have informed vaccine development. New adjuvants and delivery systems are being designed based upon their capacity to stimulate innate immune sensors and target antigens to dendritic cells, the cells responsible for initiating adaptive immune responses. Incorporating these adjuvants and delivery systems in vaccines can beneficially alter the quantitative and qualitative nature of the adaptive immune response, resulting in enhanced protection.

  10. The introduction of new vaccines into developing countries II. Vaccine financing.

    Science.gov (United States)

    Mahoney, R T; Ramachandran, S; Xu, Z

    2000-06-01

    The development of new vaccines for important childhood diseases presents an unparalleled opportunity for disease control but also a significant problem for developing countries: how to pay for them. To help address this problem, the William H. Gates Foundation has established a Global Fund for Children's Vaccine. In this paper, we discuss the allocation of this and other similar funds, which we call Global Funds. We propose that allocation of the Global Funds to individual countries be guided in part by a Vaccine Procurement Baseline (VPB). The VPB would set a minimum of 0.01% of gross national product (GNP) as an amount each developing country would devote to its own vaccine procurement. When this amount is not sufficient to procure the vaccines needed by a developing country, the Global Funds would meet the shortfall. The amount required of donors to maintain the Global Funds would be about $403 million per year for both existing EPI vaccines as well as for a hypothetical group of five new vaccines costing $0.50 per dose and requiring three doses per child. Including program costs, poor developing countries currently spend about 0.13% of GNP on EPI immunizations. In contrast, the United States, as one example donor country, spends about 0.035% of GNP for childhood immunization including several new vaccines. This paper analyzes the Global Funds requirements for hepatitis B and Haemophilus influenzae type b (Hib) vaccines. After a ramp-up period, needier countries would eventually require about $62 million for hepatitis B and $282 million for Hib at current prices. Various additional criteria could be used to qualify countries for participation in the Global Funds.

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

    Directory of Open Access Journals (Sweden)

    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

  12. Therapeutic vaccines for cancer: an overview of clinical trials.

    Science.gov (United States)

    Melero, Ignacio; Gaudernack, Gustav; Gerritsen, Winald; Huber, Christoph; Parmiani, Giorgio; Scholl, Suzy; Thatcher, Nicholas; Wagstaff, John; Zielinski, Christoph; Faulkner, Ian; Mellstedt, Håkan

    2014-09-01

    The therapeutic potential of host-specific and tumour-specific immune responses is well recognized and, after many years, active immunotherapies directed at inducing or augmenting these responses are entering clinical practice. Antitumour immunization is a complex, multi-component task, and the optimal combinations of antigens, adjuvants, delivery vehicles and routes of administration are not yet identified. Active immunotherapy must also address the immunosuppressive and tolerogenic mechanisms deployed by tumours. This Review provides an overview of new results from clinical studies of therapeutic cancer vaccines directed against tumour-associated antigens and discusses their implications for the use of active immunotherapy.

  13. Comparative evaluation of techniques for the manufacturing of dendritic cell-based cancer vaccines.

    Science.gov (United States)

    Dohnal, Alexander Michael; Graffi, Sebastian; Witt, Volker; Eichstill, Christina; Wagner, Dagmar; Ul-Haq, Sidrah; Wimmer, Doris; Felzmann, Thomas

    2009-01-01

    Manufacturing procedures for cellular therapies are continuously improved with particular emphasis on product safety. We previously developed a dendritic cell (DC) cancer vaccine technology platform that uses clinical grade lipopolysaccharide (LPS) and interferon (IFN)-y for the maturation of monocyte derived DCs. DCs are frozen after 6 hrs exposure at a semi-mature stage (smDCs) retaining the capacity to secret interleukin (IL)-12 and thus support cytolytic T-cell responses, which is lost at full maturation. We compared closed systems for monocyte enrichment from leucocyte apheresis products from healthy individuals using plastic adherence, CD14 selection, or CD2/19 depletion with magnetic beads, or counter flow centrifugation (elutriation) using a clinical grade in comparison to a research grade culture medium for the following DC generation. We found that elutriation was superior compared to the other methods showing 36 +/- 4% recovery, which was approximately 5-fold higher as the most frequently used adherence protocol (8 +/- 1%), and a very good purity (92 +/- 5%) of smDCs. Immune phenotype and IL-12 secretion (adherence: 1.4 +/- 0.4; selection: 20 +/- 0.6; depletion: 1 +/-0.5; elutriation: 3.6 +/- 1.5 ng/ml) as well as the potency of all DCs to stimulate T cells in an allogeneic mixed leucocyte reaction did not show statistically significant differences. Research grade and clinical grade DC culture media were equally potent and freezing did not impair the functions of smDCs. Finally, we assessed the functional capacity of DC cancer vaccines manufactured for three patients using this optimized procedure thereby demonstrating the feasibility of manufacturing DC cancer vaccines that secret IL-12 (9.4 +/- 6.4 ng/ml). We conclude that significant steps were taken here towards clinical grade DC cancer vaccine manufacturing.

  14. Novel approaches to foot-and-mouth disease vaccine development

    Science.gov (United States)

    The need for better Foot-and-mouth disease (FMD) vaccines is not new, a report from the Research Commission on FMD, authored by F. Loeffler and P. Frosch in 1897, highlighted the need for developing a vaccine against FMD and qualified this as a devastating disease causing “severe economic damage to ...

  15. The Development of Vaccination and the Discoveries of Louis Pasteur.

    Science.gov (United States)

    Williams, James

    1992-01-01

    Describes the development of vaccination and provides a brief biographical sketch of the life and work of Pasteur. Describes historical practices related to vaccination before Pasteur did his work, including variolation as practiced by the ancient Chinese and Jenner's use of smallpox. (PR)

  16. Developments of Subunit and VLP Vaccines Against Influenza A Virus

    Institute of Scientific and Technical Information of China (English)

    Ma-ping Deng; Zhi-hong Hu; Hua-lin Wang; Fei Deng

    2012-01-01

    Influenza virus is a continuous and severe global threat to mankind.The continuously re-emerging disease gives rise to thousands of deaths and enormous economic losses each year,which emphasizes the urgency and necessity to develop high-quality influenza vaccines in a safer,more efficient and economic way.The influenza subunit and VLP vaccines,taking the advantage of recombinant DNA technologies and expression system platforms,can be produced in such an ideal way.This review summarized the recent advancements in the research and development of influenza subunit and VLP vaccines based on the recombinant expression of hemagglutinin antigen (HA),neuraminidase antigen (NA),Matrix 2 protein (M2) and nucleocapsid protein (NP).It would help to get insight into the current stage of influenza vaccines,and suggest the future design and development of novel influenza vaccines.

  17. Typhoid fever & vaccine development: a partially answered question.

    Science.gov (United States)

    Marathe, Sandhya A; Lahiri, Amit; Negi, Vidya Devi; Chakravortty, Dipshikha

    2012-01-01

    Typhoid fever is a systemic disease caused by the human specific Gram-negative pathogen Salmonella enterica serovar Typhi (S. Typhi). The extra-intestinal infections caused by Salmonella are very fatal. The incidence of typhoid fever remains very high in impoverished areas and the emergence of multidrug resistance has made the situation worse. To combat and to reduce the morbidity and mortality caused by typhoid fever, many preventive measures and strategies have been employed, the most important being vaccination. In recent years, many Salmonella vaccines have been developed including live attenuated as well as DNA vaccines and their clinical trials have shown encouraging results. But with the increasing antibiotic resistance, the development of potent vaccine candidate for typhoid fever is a need of the hour. This review discusses the latest trends in the typhoid vaccine development and the clinical trials which are underway.

  18. The future of cancer research: prevention, screening, vaccines, and tumor-specific drug combos.

    Science.gov (United States)

    Blanck, George

    2014-01-01

    New cancer research strategies have developed very rapidly over the past five years, including extensive DNA sequencing of tumor and normal cells; use of highly sensitive cancer cell detection methods; vaccine development and tumor-specific (designer) drugs. These developments have raised questions about where to concentrate efforts in the near future when establishing clinical trials, particularly important in an age of diminishing resources and during a period when competing strategies for cancer control are likely to overwhelm the opportunities for establishing large, effective clinical trials. In particular, it behooves the research community to be mindful of the inevitable, challenging obligation to responsibly choose between clinical trials that offer the credible hope of incremental advances vs. trials that are less traditional but may have revolutionary outcomes.

  19. Vaccine development for Tuberculosis: Past, Present and Future Challenges

    Directory of Open Access Journals (Sweden)

    Dileep Tiwari

    2011-06-01

    Full Text Available About one third of the world's population is infected with Mycobacterium tuberculosis (M. tb, and new infections occur at a rate of about one per second. Additionally, more people in the developed world contact tuberculosis (TB because their immune systems are more likely to be compromised due to higher exposure to immunosuppressive drugs, substance abuse, or AIDS. The distribution of tuberculosis is not uniform across the globe, still the treatment is difficult and requires long courses of multiple antibiotics. However, antibiotic resistance is a growing problem in multidrugresistant (MDR tuberculosis. But mostly the prevention relies on screening programs and vaccination, usually with Bacillus Calmette- Guérin (BCG vaccine. BCG is the most commonly used vaccine worldwide, but not as a powerful vaccine. BCG also provides some protection against severe forms of pediatric TB, but has been shown to be unreliable against adult pulmonary TB which accounts for most of the disease burden worldwide. Currently, there is an urgent need for novel, more effective vaccine that can prevent all forms of TB including drug resistant strains for all age groups and among people with HIV. The first recombinant tuberculosis vaccine rBCG30, entered clinical trials in year 2004, but, still no effective vaccine is available in a market. Study showed that DNA TB vaccine given with conventional chemotherapy can accelerate the disappearance of bacteria as well as protect against re-infection in mice and it is quite effective against TB. A very promising TB vaccine, MVA85A, is currently in phase II trials and is based on a genetically modified vaccinia virus. Many other strategies are also being used to develop novel vaccines, including both subunit vaccines such as Hybrid-1, HyVac4 or M72, and recombinant adenoviruses such as Ad35. Some of these vaccines can be effectively administered without needles making them preferable for areas where HIV is very common and few of

  20. Accelerating the development of a safe and effective HIV vaccine: HIV vaccine case study for the Decade of Vaccines.

    Science.gov (United States)

    Koff, Wayne C; Russell, Nina D; Walport, Mark; Feinberg, Mark B; Shiver, John W; Karim, Salim Abdool; Walker, Bruce D; McGlynn, Margaret G; Nweneka, Chidi Victor; Nabel, Gary J

    2013-04-18

    Human immunodeficiency virus (HIV), the etiologic agent that causes AIDS, is the fourth largest killer in the world today. Despite the remarkable achievements in development of anti-retroviral therapies against HIV, and the recent advances in new prevention technologies, the rate of new HIV infections continue to outpace efforts on HIV prevention and control. Thus, the development of a safe and effective vaccine for prevention and control of AIDS remains a global public health priority and the greatest opportunity to eventually end the AIDS pandemic. Currently, there is a renaissance in HIV vaccine development, due in large part to the first demonstration of vaccine induced protection, albeit modest, in human efficacy trials, a generation of improved vaccine candidates advancing in the clinical pipeline, and newly defined targets on HIV for broadly neutralizing antibodies. The main barriers to HIV vaccine development include the global variability of HIV, lack of a validated animal model, lack of correlates of protective immunity, lack of natural protective immune responses against HIV, and the reservoir of infected cells conferred by integration of HIV's genome into the host. Some of these barriers are not unique to HIV, but generic to other variable viral pathogens such as hepatitis C and pandemic influenza. Recommendations to overcome these barriers are presented in this document, including but not limited to expansion of efforts to design immunogens capable of eliciting broadly neutralizing antibodies against HIV, expansion of clinical research capabilities to assess multiple immunogens concurrently with comprehensive immune monitoring, increased support for translational vaccine research, and engaging industry as full partners in vaccine discovery and development.

  1. Human papilloma viruses and cancer in the post-vaccine era.

    Science.gov (United States)

    Galani, E; Christodoulou, C

    2009-11-01

    Human papilloma viruses (HPV) are strong human carcinogens, in fact today they are considered as the second most frequent carcinogen. In the middle of the 1970s the hypothesis that cervical cancer may arise from viruses was established and in the 1990s the relationship between HPV and cervical neoplasia was confirmed. HPV infections are the most common sexually transmitted infections. Specific subtypes of human papilomaviruses are now considered as the etiological agents in nearly all cases of cervical cancer and cervical epithelial neoplasia. Approximately 470,000 new cases and 23,000 deaths of cervical cancer occur each year, with the majority taking place in developing countries. Cervical cancer remains among the three leading causes of cancer deaths among women below the age of 45. Human papilomaviruses are classified into two groups: high-risk (oncogenic) types and low risk types. HPV types 16, 18, 45 and 31 are considered to be the most important oncogenic types. Subtypes 16 and 18 are the causative agents of more than 50% of cervical pre-cancerous lesions, and more than 70% of cervical cancer cases. High risk subtypes are also implicated with anal, perianal and oropharyngeal carcinomas. Recently, the prophylactic bivalent HPV 16/18 and the quadrivalent HPV 6/11/16/18/ vaccines have been approved. The development of prophylactic vaccines against human papilomavirus has been hailed as one of the most significant advances of recent years and it is expected to reduce dramatically the mortality of human papilomavirus associated cancers, but has also given rise to some of the most intense scientific debates.

  2. Avian necrotic enteritis: Experimental models, climate change, and vaccine development

    Science.gov (United States)

    This review summarizes recent developments in disease models, pathogenesis, host immunity, risk factors, and vaccine development for Clostridium perfringens infection of poultry and necrotic enteritis (NE). The increasing trends of legislative restrictions and voluntary removal of antibiotic growth...

  3. What should vaccine developers ask? Simulation of the effectiveness of malaria vaccines.

    Directory of Open Access Journals (Sweden)

    Melissa A Penny

    Full Text Available BACKGROUND: A number of different malaria vaccine candidates are currently in pre-clinical or clinical development. Even though they vary greatly in their characteristics, it is unlikely that any of them will provide long-lasting sterilizing immunity against the malaria parasite. There is great uncertainty about what the minimal vaccine profile should be before registration is worthwhile; how to allocate resources between different candidates with different profiles; which candidates to consider combining; and what deployment strategies to consider. METHODS AND FINDINGS: We use previously published stochastic simulation models, calibrated against extensive epidemiological data, to make quantitative predictions of the population effects of malaria vaccines on malaria transmission, morbidity and mortality. The models are fitted and simulations obtained via volunteer computing. We consider a range of endemic malaria settings with deployment of vaccines via the Expanded program on immunization (EPI, with and without additional booster doses, and also via 5-yearly mass campaigns for a range of coverages. The simulation scenarios account for the dynamic effects of natural and vaccine induced immunity, for treatment of clinical episodes, and for births, ageing and deaths in the cohort. Simulated pre-erythrocytic vaccines have greatest benefits in low endemic settings (EIR of 84 PEV may lead to increased incidence of severe disease in the long term, if efficacy is moderate to low (20% malaria vaccines (either PEV or BSV when deployed through mass campaigns targeting all age-groups as well as EPI, and especially if combined with highly efficacious transmission-blocking components. CONCLUSIONS: We present for the first time a stochastic simulation approach to compare likely effects on morbidity, mortality and transmission of a range of malaria vaccines and vaccine combinations in realistic epidemiological and health systems settings. The results raise

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

    Science.gov (United States)

    Arama, C; Troye-Blomberg, M

    2014-05-01

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

  5. Status of vaccine research and development of vaccines for Nipah virus.

    Science.gov (United States)

    Satterfield, Benjamin A; Dawes, Brian E; Milligan, Gregg N

    2016-06-03

    Nipah virus (NiV) is a highly pathogenic, recently emerged paramyxovirus that has been responsible for sporadic outbreaks of respiratory and encephalitic disease in Southeast Asia. High case fatality rates have also been associated with recent outbreaks in Malaysia and Bangladesh. Although over two billion people currently live in regions in which NiV is endemic or in which the Pteropus fruit bat reservoir is commonly found, there is no approved vaccine to protect against NiV disease. This report examines the feasibility and current efforts to develop a NiV vaccine including potential hurdles for technical and regulatory assessment of candidate vaccines and the likelihood for financing.

  6. 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

  7. Vaccinations

    Science.gov (United States)

    ... vaccinated? For many years, a set of annual vaccinations was considered normal and necessary for dogs and ... to protect for a full year. Consequently, one vaccination schedule will not work well for all pets. ...

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

    Science.gov (United States)

    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.

  9. 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.

  10. Genes to vaccines for immunotherapy: how the molecular biology revolution has influenced cancer immunology.

    Science.gov (United States)

    Laheru, Dan A; Pardoll, Drew M; Jaffee, Elizabeth M

    2005-11-01

    Recent advances in our understanding of the complex signaling pathways involved in immune system regulation, along with analyses of genetic differences between tumors and their normal cellular counterparts, have accelerated development of immune-based strategies for cancer treatment and prevention. More clinically relevant animal models have shown that successful immune-based strategies will require the integration of interventions that target specific tumor antigens with regulators of the antitumor immune response. Immunotherapy for cancer is at a critical crossroad, as therapeutics designed to target cancer-associated antigens and regulatory signaling molecules enter clinical trials. We outline here a paradigm for early-stage clinical development of immunotherapy combinations that use vaccines to drive tumor antigen-specific responses while simultaneously targeting immune regulatory pathways.

  11. Vaccination with Necroptotic Cancer Cells Induces Efficient Anti-tumor Immunity.

    Science.gov (United States)

    Aaes, Tania Løve; Kaczmarek, Agnieszka; Delvaeye, Tinneke; De Craene, Bram; De Koker, Stefaan; Heyndrickx, Liesbeth; Delrue, Iris; Taminau, Joachim; Wiernicki, Bartosz; De Groote, Philippe; Garg, Abhishek D; Leybaert, Luc; Grooten, Johan; Bertrand, Mathieu J M; Agostinis, Patrizia; Berx, Geert; Declercq, Wim; Vandenabeele, Peter; Krysko, Dmitri V

    2016-04-12

    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.

  12. Prospects for the development of fungal vaccines.

    OpenAIRE

    Deepe, G S

    1997-01-01

    In an era that emphasizes the term "cost-effective," vaccines are the ideal solution to preventing disease at a relatively low cost to society. Much of the previous emphasis has been on childhood scourges such as measles, mumps, rubella, poliomyelitis, and Haemophilus influenzae type b. The concept of vaccines for fungal diseases has had less impact because of the perceived limited problem. However, fungal diseases have become increasingly appreciated as serious medical problems that require ...

  13. [Development of Nucleic Acid-Based Adjuvant for Cancer Immunotherapy].

    Science.gov (United States)

    Kobiyama, Kouji; Ishii, Ken J

    2015-09-01

    Since the discovery of the human T cell-defined tumor antigen, the cancer immunotherapy field has rapidly progressed, with the research and development of cancer immunotherapy, including cancer vaccines, being conducted actively. However, the disadvantages of most cancer vaccines include relatively weak immunogenicity and immune escape or exhaustion. Adjuvants with innate immunostimulatory activities have been used to overcome these issues, and these agents have been shown to enhance the immunogenicity of cancer vaccines and to act as mono-therapeutic anti-tumor agents. CpG ODN, an agonist for TLR9, is one of the promising nucleic acid-based adjuvants, and it is a potent inducer of innate immune effector functions. CpG ODN suppresses tumor growth in the absence of tumor antigens and peptide administration. Therefore, CpG ODN is expected to be useful as a cancer vaccine adjuvant as well as a cancer immunotherapy agent. In this review, we discuss the potential therapeutic applications and mechanisms of CpG ODN for cancer immunotherapy.

  14. 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

    2014-01-01

    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.

  15. EVOLUTION OF MYCOBACTERIUM TUBERCULOSIS AND IMPLICATIONS FOR VACCINE DEVELOPMENT.

    Science.gov (United States)

    Gagneux, Sebastien

    2016-04-01

    Tuberculosis (TB) is a growing public health threat, particularly in the face of the global epidemics of multidrug resistance. Given the limited efficacy of the current TB vaccine and the recent clinical failure of the most advanced new TB vaccine candidate, novel concepts for vaccine design should be explored. Most T cell antigens in the human-adapted Mycobacterium tuberculosis complex (MTBC) are evolutionarily conserved and under strong purifying selection, indicating that host immune responses targeting these antigens might not be protective. By contrast, a few highly variable T cell epitopes have recently been discovered, which could serve as alternative vaccine antigens. Moreover, there is increasing evidence that the human-adapted MTBC has been co-evolving with the human host for a long time. Hence, studying the interaction between bacterial and human genetic diversity might help identify additional targets that could be exploited for TB vaccine development.

  16. Status of paratyphoid fever vaccine research and development.

    Science.gov (United States)

    Martin, Laura B; Simon, Raphael; MacLennan, Calman A; Tennant, Sharon M; Sahastrabuddhe, Sushant; Khan, M Imran

    2016-06-01

    Salmonella enterica serovars Typhi and Paratyphi (S. Paratyphi) A and B cause enteric fever in humans. Of the paratyphoid group, S. Paratyphi A is the most common serovar. In 2000, there were an estimated 5.4 million cases of S. Paratyphi A worldwide. More recently paratyphoid fever has accounted for an increasing fraction of all cases of enteric fever. Although vaccines for typhoid fever have been developed and in use for decades, vaccines for paratyphoid fever have not yet been licensed. Several S. Paratyphi A vaccines, however, are in development and based on either whole cell live-attenuated strains or repeating units of the lipopolysaccharide O-antigen (O:2) conjugated to different protein carriers. An O-specific polysaccharide (O:2) of S. Paratyphi A conjugated to tetanus toxoid (O:2-TT), for example, has been determined to be safe and immunogenic after one dose in Phase I and Phase II trials. Two other conjugated vaccine candidates linked to diphtheria toxin and a live-attenuated oral vaccine candidate are currently in preclinical development. As promising vaccine candidates are advanced along the development pipeline, an adequate supply of vaccines will need to be ensured to meet growing demand, particularly in the most affected countries.

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

    Science.gov (United States)

    Barbosa, T; Barral-Netto, M

    2013-02-01

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

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

    Directory of Open Access Journals (Sweden)

    T. Barbosa

    2013-02-01

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

  19. Novel adjuvants & delivery vehicles for vaccines development: a road ahead.

    Science.gov (United States)

    Mohan, Teena; Verma, Priyanka; Rao, D Nageswara

    2013-11-01

    The pure recombinant and synthetic antigens used in modern day vaccines are generally less immunogenic than older style live/attenuated and killed whole organism vaccines. One can improve the quality of vaccine production by incorporating immunomodulators or adjuvants with modified delivery vehicles viz. liposomes, immune stimulating complexes (ISCOMs), micro/nanospheres apart from alum, being used as gold standard. Adjuvants are used to augment the effect of a vaccine by stimulating the immune system to respond to the vaccine, more vigorously, and thus providing increased immunity to a particular disease. Adjuvants accomplish this task by mimicking specific sets of evolutionary conserved molecules which include lipopolysaccharides (LPS), components of bacterial cell wall, endocytosed nucleic acids such as dsRNA, ssDNA and unmethylated CpG dinucleotide containing DNA. This review provides information on various vaccine adjuvants and delivery vehicles being developed to date. From literature, it seems that the humoral immune responses have been observed for most adjuvants and delivery platforms while viral-vector, ISCOMs and Montanides have shown cytotoxic T-cell response in the clinical trials. MF59 and MPL® have elicited Th1 responses, and virus-like particles (VLPs), non-degradable nanoparticle and liposomes have also generated cellular immunity. Such vaccine components have also been evaluated for alternative routes of administration with clinical success reported for intranasal delivery of viral-vectors and proteosomes and oral delivery of VLP vaccines.

  20. Cross-stage immunity for malaria vaccine development.

    Science.gov (United States)

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

    2015-12-22

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

  1. Advances in the development of vaccines for dengue fever

    Directory of Open Access Journals (Sweden)

    Simmons M

    2012-05-01

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

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

    Science.gov (United States)

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

    2016-05-12

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

  3. Vaccinomics and personalized vaccinology: is science leading us toward a new path of directed vaccine development and discovery?

    Science.gov (United States)

    Poland, Gregory A; Kennedy, Richard B; Ovsyannikova, Inna G

    2011-12-01

    As is apparent in many fields of science and medicine, the new biology, and particularly new high-throughput genetic sequencing and transcriptomic and epigenetic technologies, are radically altering our understanding and views of science. In this article, we make the case that while mostly ignored thus far in the vaccine field, these changes will revolutionize vaccinology from development to manufacture to administration. Such advances will address a current major barrier in vaccinology-that of empiric vaccine discovery and development, and the subsequent low yield of viable vaccine candidates, particularly for hyper-variable viruses. While our laboratory's data and thinking (and hence also for this paper) has been directed toward viruses and viral vaccines, generalization to other pathogens and disease entities (i.e., anti-cancer vaccines) may be appropriate.

  4. Vaccinomics and personalized vaccinology: is science leading us toward a new path of directed vaccine development and discovery?

    Directory of Open Access Journals (Sweden)

    Gregory A Poland

    2011-12-01

    Full Text Available As is apparent in many fields of science and medicine, the new biology, and particularly new high-throughput genetic sequencing and transcriptomic and epigenetic technologies, are radically altering our understanding and views of science. In this article, we make the case that while mostly ignored thus far in the vaccine field, these changes will revolutionize vaccinology from development to manufacture to administration. Such advances will address a current major barrier in vaccinology-that of empiric vaccine discovery and development, and the subsequent low yield of viable vaccine candidates, particularly for hyper-variable viruses. While our laboratory's data and thinking (and hence also for this paper has been directed toward viruses and viral vaccines, generalization to other pathogens and disease entities (i.e., anti-cancer vaccines may be appropriate.

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

    Science.gov (United States)

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

    2016-11-11

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

  6. Streptococcus pneumoniae proteomics: determinants of pathogenesis and vaccine development.

    Science.gov (United States)

    Bittaye, Mustapha; Cash, Phil

    2015-01-01

    Streptococcus pneumoniae is a major pathogen that is responsible for a variety of invasive diseases. The bacteria gain entry initially by establishing a carriage state in the nasopharynx from where they migrate to other sites in the body. The worldwide distribution of the bacteria and the severity of the diseases have led to a significant level of interest in the development of vaccines against the bacteria. Current vaccines, based on the bacterial polysaccharide, have a number of limitations including poor immunogenicity and limited effectiveness against all pneumococcal serotypes. There are many challenges in developing vaccines that will be effective against the diverse range of isolates and serotypes for this highly variable bacterial pathogen. This review considers how proteomic technologies have extended our understanding of the pathogenic mechanisms of nasopharyngeal colonization and disease development as well as the critical areas in developing protein-based vaccines.

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

    Science.gov (United States)

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

    2011-05-01

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

  8. Promoting HIV vaccine research and development in China

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    @@ Anational strategy for the HIV vaccine research and development (R&D) should be formulated as soon as possible so as to ensure a sound progress in this field, urges a report by the Academic Divisions of the Chinese Academy of Sciences (CASAD), the top national advisory body in science and technology. Entitled "A Proposal on China's Strategy of the HIV Vaccine Research and Development,"the report has recently been submitted to the State Council, the country's cabinet.

  9. The development of an AIDS vaccine: progress and promise.

    OpenAIRE

    Fauci, A S; Fischinger, P J

    1988-01-01

    The development of a safe and effective vaccine against infection by the human immunodeficiency virus (HIV) is of paramount importance to the prevention of AIDS worldwide. Although a great deal has been learned about HIV in a few short years, the development of an AIDS vaccine has proved to be extremely difficult. The lack of an appropriate animal model for AIDS, the absence of a defined protective immune response in persons infected with HIV, the long latent period between initial infection ...

  10. Cancer Vaccine by Fusions of Dendritic and Cancer Cells

    OpenAIRE

    Shigeo Koido; Eiichi Hara; Sadamu Homma; Yoshihisa Namiki; Toshifumi Ohkusa; Jianlin Gong; Hisao Tajiri

    2010-01-01

    Dendritic cells (DCs) are potent antigen-presenting cells and play a central role in the initiation and regulation of primary immune responses. Therefore, their use for the active immunotherapy against cancers has been studied with considerable interest. The fusion of DCs with whole tumor cells represents in many ways an ideal approach to deliver, process, and subsequently present a broad array of tumor-associated antigens, including those yet to be unidentified, in the context of DCs-derived...

  11. Prospects for primary prevention of cervical cancer in developing countries

    Directory of Open Access Journals (Sweden)

    Franceschi Silvia

    2003-01-01

    Full Text Available The HPV types that cause cervical cancer are sexually transmitted, but there is little evidence that infection can be avoided by behavioural changes, such as condom use. In contrast, prophylactic vaccines against HPV infection are likely to have high efficacy. In principle, the effectiveness of HPV vaccination as a strategy for cervical cancer control can be measured either by monitoring secular trends in cervical cancer incidence or by conducting randomized trials. The former approach is unlikely to provide convincing evidence of effectiveness, since cervical cancer rates are subject to strong secular trends that are independent of intervention measures. A few phase III trials of HPV prophylactic vaccines are now being started. Such trials are very expensive studies involving frequent and complicated investigations. It is important, however, to start as soon as possible simpler trials designed to demonstrate the effectiveness of HPV vaccine in field conditions, i.e. in developing or intermediate countries which suffer the major burden of mortality from cervical cancer. Such trials may capture a difference in the most severe, and rarest, preinvasive cervical lesions (i.e., the real target of any HPV vaccine over a prolonged follow-up (20 years at least. The design of such studies is briefly considered for two areas: Southern India and South Korea.

  12. Comparison of accelerated and rapid schedules for monovalent hepatitis B and combined hepatitis A/B vaccines in children with cancer.

    Science.gov (United States)

    Köksal, Yavuz; Varan, Ali; Aydin, G Burca; Sari, Neriman; Yazici, Nalan; Yalcin, Bilgehan; Kutluk, Tezer; Akyuz, Canan; Büyükpamukçu, Münevver

    2007-12-01

    The aim of this study was to determine the efficacy of immunization against hepatitis A and B infections with "rapid" or "accelerated" schedules in children with cancer receiving chemotherapy. Fifty-one children were recruited to receive either vaccination schedule, in the "rapid vaccination schedule"; hepatitis B (group I) or combined hepatitis A/B vaccines (group III) were administered at months 0, 1, 2, and 12; in the "accelerated vaccination schedule," hepatitis B (group II) or combined hepatitis A/B (group IV) vaccines were administered on days 0, 7, 21, and 365 intramuscularly. The seroconversion rates at months 1 and 3 were 35.7 and 57.1% in group I and 25 and 18.8% in group II, respectively. Group I developed higher seroconversion rates at month 3. In group III the seroconversion rates for hepatitis B at months 1 and 3 were 54.5 and 60% and in group IV 50 and 70%, respectively. For hepatitis A, the seroconversion rates at months 1 and 3 were 81.8 and 90% in group III and 80 and 88.9% in group IV, respectively. The accelerated vaccination schedule seems to have no advantage in children receiving cancer chemotherapy except for high antibody levels at month 1. In conclusion, the accelerated vaccination schedules are not good choices for cancer patients. The combined hepatitis A/B vaccine is more effective than monovalent vaccine in cancer patients, which probably can be explained by an adjuvant effect of the antigens. The seroconversion of hepatitis A by the combined hepatitis A/B vaccination is very good in cancer patients.

  13. 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

  14. 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...... on dendritic cells pulsed with an allogenic tumor cell lysate. Twenty patients with advanced colorectal cancer were consecutively enrolled. Dendritic cells (DC) were generated from autologous peripheral blood mononuclear cells and pulsed with allogenic tumor cell lysate containing high levels of cancer...

  15. Implications of plant glycans in the development of innovative vaccines.

    Science.gov (United States)

    Rosales-Mendoza, Sergio; Salazar-González, Jorge A; Decker, Eva L; Reski, Ralf

    2016-07-01

    Plant glycans play a central role in vaccinology: they can serve as adjuvants and/or delivery vehicles or backbones for the synthesis of conjugated vaccines. In addition, genetic engineering is leading to the development of platforms for the production of novel polysaccharides in plant cells, an approach with relevant implications for the design of new types of vaccines. This review contains an updated outlook on this topic and provides key perspectives including a discussion on how the molecular pharming field can be linked to the production of innovative glycan-based and conjugate vaccines.

  16. FDA Approves Two HPV Vaccines: Cervarix for Girls, Gardasil for Boys | Division of Cancer Prevention

    Science.gov (United States)

    The FDA has approved a second vaccine to prevent cervical cancer and cervical precancers, the vaccine’s manufacturer, GlaxoSmithKline (GSK), announced last week. The approval is based on data from a large clinical trial showing that the vaccine, Cervarix, prevented precancerous lesions in 93 percent of those who received the full vaccine sequence of three injections over 6 months. |

  17. Systems biology applied to vaccine and immunotherapy development

    Directory of Open Access Journals (Sweden)

    Marincola Francesco M

    2011-09-01

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

  18. Risk in vaccine research and development quantified

    NARCIS (Netherlands)

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

    2013-01-01

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

  19. Risk in Vaccine Research and Development Quantified

    NARCIS (Netherlands)

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

    2013-01-01

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

  20. Clinical development of placental malaria vaccines and immunoassays harmonization

    DEFF Research Database (Denmark)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2007-11-01

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

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

    Science.gov (United States)

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

    2014-08-01

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

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

    Science.gov (United States)

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

    2012-01-01

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

  4. Platform for Plasmodium vivax vaccine discovery and development.

    Science.gov (United States)

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

    2011-08-01

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

  5. Optimal Finite Cancer Treatment Duration by Using Mixed Vaccine Therapy and Chemotherapy: State Dependent Riccati Equation Control

    Directory of Open Access Journals (Sweden)

    Ali Ghaffari

    2014-01-01

    Full Text Available The main objective of this paper is to propose an optimal finite duration treatment method for cancer. A mathematical model is proposed to show the interactions between healthy and cancerous cells in the human body. To extend the existing models, the effect of vaccine therapy and chemotherapy are also added to the model. The equilibrium points and the related local stability are derived and discussed. It is shown that the dynamics of the cancer model must be changed and modified for finite treatment duration. Therefore, the vaccine therapy is used to change the parameters of the system and the chemotherapy is applied for pushing the system to the domain of attraction of the healthy state. For optimal chemotherapy, an optimal control is used based on state dependent Riccati equation (SDRE. It is shown that, in spite of eliminating the treatment, the system approaches the healthy state conditions. The results show that the development of optimal vaccine-chemotherapy protocols for removing tumor cells would be an appropriate strategy in cancer treatment. Also, the present study states that a proper treatment method not only reduces the population of the cancer cells but also changes the dynamics of the cancer.

  6. Immunotherapeutic Vaccine as an Alternative Treatment to Overcome Drug-Resistant Ovarian Cancer

    Science.gov (United States)

    2012-07-01

    cells by polyvalent Listeria monocytogenes-based vaccines. J Immunother 32:856-69. 6. Karkada M, Weir, G.M., Quinton,T., Sammatur, L., MacDonald, L.D...polyva- lent Listeria monocytogenes-based vaccines. J Immunother 2009; 32:856–69. 6 Karkada M, Weir GM, Quinton T et al. A novel breast/ovarian cancer

  7. Preventing cervical cancer and genital warts - How much protection is enough for HPV vaccines?

    Science.gov (United States)

    Stanley, Margaret

    2016-07-01

    HPV associated disease is a global health problem: 5.2% of all cancers are HPV associated with HPV 16 and 18 accounting for 70% of cases of cervical cancer. Genital warts caused by HPV 6 and 11 have a lifetime risk of acquisition of 10%. HPV vaccines are subunit vaccines consisting of virus like particles comprised of the L1 major capsid protein. Two vaccines have been licenced since 2006/2007 and are in the National Immunisation programmes in 62 countries. Both vaccines include HPV 16 and 18 VLPs and one also includes HPV 6 and 11. The vaccines are highly immunogenic and well tolerated. Genital HPV is a sexually transmitted infection with peak incidence occurring just after the onset of sexual activity and the routine cohort for immunisation in almost all countries are adolescent girls 9-15 years of age with or without catch up for older adolescents and young women. Population effectiveness is now being demonstrated for these vaccines in countries with high vaccine coverage. HPV vaccines are highly immunogenic and effective and the original 3 dose schedules have already been reduced, for those 14 years and under, to 2 for both licenced vaccines. There is preliminary evidence that 1 dose of vaccine is as effective as 2 or 3 in preventing persistent HPV infection in the cervix in young women and further reductions in dosage may be possible if supported by appropriate virological, immunological and modelling studies.

  8. Development of Contagious Caprine Pleuropneumonia Inactivated Vaccine( M1601 Strain)

    Institute of Scientific and Technical Information of China (English)

    Zhao; Ping; He; Ying; Chu; Yuefeng; Gao; Pengcheng; Zhang; Xuan; Lu; Zhongxin

    2014-01-01

    Three batches of contagious caprine pleuropneumonia inactivated vaccine( M1601 strain) developed by the laboratory were studied from the aspects of safety,minimum immune dose,immunity duration and storage life. The results showed that the vaccine was safe to goats under different physiological conditions.Regardless of lambs or adult goats,the minimum immune dose was 3 m L,and the immunity duration and the storage life were 6 and 12 months,respectively.

  9. The Capricious Nature of Bacterial Pathogens: Phasevarions and Vaccine Development

    OpenAIRE

    Aimee Tan; Atack, John M.; Jennings, Michael P; Seib, Kate L.

    2016-01-01

    Infectious diseases are a leading cause of morbidity and mortality worldwide, and vaccines are one of the most successful and cost-effective tools for disease prevention. One of the key considerations for rational vaccine development is the selection of appropriate antigens. Antigens must induce a protective immune response, and this response should be directed to stably expressed antigens so the target microbe can always be recognized by the immune system. Antigens with variable expression, ...

  10. Development and clinical application of new polyvalent combined paediatric vaccines.

    Science.gov (United States)

    André, F E

    1999-03-26

    The availability of combined vaccines containing protective antigens against the majority of (ideally all) diseases for which universal immunization is recommended in infancy would simplify the implementation, increase the acceptance, reduce the global cost of immunization programmes and improve disease control, while offering the possibility of disease elimination or even pathogen eradication. The desirability of combined vaccines is further enhanced, and made more urgent, because of the increasing number of diseases that can be prevented by vaccination. The complicated logistics of administering different vaccines that each require several inoculations is a significant barrier to successful immunization of a population. Furthermore, interest in immunization is continuously gaining momentum since it is now generally recognised that vaccines are among the safest and most cost-effective medical interventions for infectious diseases that continue, in spite of the widespread use of efficacious antimicrobial drugs, to be an important cause of morbidity and mortality. This burden is likely to increase due to the development of antimicrobial resistance. Basic research on new vaccines or improvement of existing ones such as the use of new technologies may be carried out in academic or other non-industrial laboratories but development work, including the necessary extensive clinical testing, that lead to products that can be approved for routine use is usually co-ordinated and financed by commercial companies. The decision to develop any particular combined vaccine will therefore be influenced not only by its medical desirability and technical feasibility but also the potential financial returns that the required investments in time and resources may bring to the company. All major vaccine manufacturers are currently working, either alone or through strategic alliances, towards developing more polyvalent vaccines by adding antigens such as inactivated polio virus

  11. Role of vaccine manufacturers in developing countries towards global healthcare by providing quality vaccines at affordable prices.

    Science.gov (United States)

    Jadhav, S; Gautam, M; Gairola, S

    2014-05-01

    Vaccines represent one of the greatest achievements of science and medicine in the fight against infectious diseases. Vaccination is one of the most cost-effective public health tools to prevent infectious diseases. Significant progress has been made in expanding the coverage of vaccines globally, resulting in the prevention of more than two million deaths annually. In 2010, nearly 200 countries endorsed a shared vision to extend the benefits of vaccines to every person by 2020, known as the Decade of Vaccine Initiative (DoV). Vaccine manufacturers in developing countries, as represented by the Developing Countries Vaccine Manufacturers Network (DCVMN), make a significant contribution to DoV by supplying quality vaccines at affordable prices to the people who need them most. About 70% of the global Expanded Program on Immunization (EPI) vaccine supplies are met by DCVMN. Besides EPI vaccine supplies, DCVMN is also targeting vaccines against rotavirus, Japanese encephalitis, pneumonia, human papillomavirus, meningitis and neglected tropical diseases. This article reviews the roles and contributions of DCVMN in making the vaccines accessible and affordable to all.

  12. Therapeutic cancer vaccine fulfills the promise of immunotherapy in prostate cancer

    OpenAIRE

    Madan, Ravi A; Gulley, James L.

    2011-01-01

    For many years, preclinical and clinical studies have attempted to harness the power of the immune system and focus it on malignant cells in an attempt to improve clinical outcomes for patients with cancer. The current paper describes the landmark phase III trial that led to the first U.S. Food and Drug Administration approval of a therapeutic cancer vaccine. In a randomized trial of 512 patients, those treated with sipuleucel-T survived for 25.8 months compared to those treated with placebo,...

  13. WT1 Peptide Cancer Vaccine for Patients with Hematopoietic Malignancies and Solid Cancers

    Directory of Open Access Journals (Sweden)

    Yoshihiro Oka

    2007-01-01

    Full Text Available Wild-type Wilms' tumor gene WT1 is expressed at a high level in hematopoietic malignancies including acute leukemia, chronic myelogenous leukemia, and myelodysplastic syndromes, as well as in various kinds of solid cancers. Human cytotoxic T lymphocytes (CTLs, which could specifically lyse WT1-expressing tumor cells with HLA class I restriction, were generated in vitro. It was also demonstrated that mice immunized with the WT1 peptide rejected challenges by WT1-expressing cancer cells and survived with no signs of autoaggression to normal organs that physiologically expressed WT1. Furthermore, we and others detected IgM and IgG WT1 antibodies in patients with hematopoietic malignancies, indicating that the WT1 protein was highly immunogenic, and that immunoglobulin class-switch-inducing, WT1-specific, cellular immune responses were elicited in these patients. CD8+ WT1-specific CTLs were also detected in peripheral blood or tumor-draining lymph nodes of cancer patients. These results provided us with the rationale for elicitation of CTL responses targeting the WT1 product for cancer immunotherapy. On the basis of these findings, we performed a phase I clinical trial of a WT1 peptide cancer vaccine for the patients with malignant neoplasms. These results strongly suggested that the WT1 peptide cancer vaccine had efficacy in the clinical setting because clinical responses, including reduction of leukemic blast cells or regression of tumor masses, were observed after the WT1 vaccination in patients with hematopoietic malignancies or solid cancers. The power of a tumor-associated-antigen (TAA-derived cancer vaccine may be enhanced in combination with stronger adjuvants, helper peptide, molecular-target-based drugs, or some chemotherapy drugs, such as gemcitabine, which has been revealed to suppress regulartory T-cell function. In contrast, reduction of WT1 peptide dose may be needed for the treatment of patients with hematological stem cell diseases

  14. Development of a human live attenuated West Nile infectious DNA vaccine: conceptual design of the vaccine candidate.

    Science.gov (United States)

    Yamshchikov, Vladimir

    2015-10-01

    West Nile virus has become an important epidemiological problem attracting significant attention of health authorities, mass media, and the public. Although there are promising advancements toward addressing the vaccine need, the perspectives of the commercial availability of the vaccine remain uncertain. To a large extent this is due to lack of a sustained interest for further commercial development of the vaccines already undergoing the preclinical and clinical development, and a predicted insignificant cost effectiveness of mass vaccination. There is a need for a safe, efficacious and cost effective vaccine, which can improve the feasibility of a targeted vaccination program. In the present report, we summarize the background, the rationale, and the choice of the development pathway that we selected for the design of a live attenuated human West Nile vaccine in a novel infectious DNA format.

  15. Oral attenuated Salmonella typhimurium vaccine against MG7-Ag mimotope of gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Fan-Ping Meng; Jie Ding; Zhao-Cai Yu; Quan-Li Han; Chang-Cun Guo; Na Liu; Dai-Ming Fan

    2005-01-01

    AIM: To develop an oral attenuated Salmonella typhimurium vaccine against gastric cancer and to evaluate its efficacy in mice.METHODS: A complementary sequence of Nco I site and a sequence coding for MG7-Ag mimotope were designed at the 5' terminus of forward primer. Using p1.2 Ⅱ-HBCAg plasmid as template, PCR was performed to get a fusion gene of the mimotope and a HBcAg gene. The fusion gene was then subcloned into the plasmid pYA3341complementary to Salmonella typhimurium X4550, and the recombinant plasmid was then transformed into attenuated Salmonella typhimurium X4550. Balb/c mice were orally immunized with the recombinant Salmonella typhimurium X4550. The mice were immunized every 2 wk to reinforce the immunity. At the 6th wk, serum titer of antibody was detected by ELISA, and at the 8th wk,cellular immunity was detected by 51Cr release test. Ehrlich ascites carcinoma cells expressing MG7-Ag were used in tumor challenge assay as a model to evaluate the protective effect of the vaccine.RESULTS: Serum titer of antibody against MG7-Ag was significantly higher in mice immunized with the vaccine than in control groups (0.9538±0.043 vs0.6531±0.018,P<0.01; 0.9538±0.043 vs0.6915±0.012, P<0.01), while in vitro 51Cr release assay of the splenocytes showed no statistical difference in the three groups. Two weeks after tumor challenge, 1 in 5 immunized mice was tumor free, while all the mice in the control group presented tumor.CONCLUSION: Oral attenuated Salmonella typhimurium vaccine against the MG7-Ag mimotope of gastric cancer is immunogenic. It can induce significant humoral immunity against tumors in mice, and has some protective effects.

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

    Science.gov (United States)

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

    2014-12-01

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

  17. Novel vaccine development strategies for inducing mucosal immunity.

    Science.gov (United States)

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

    2012-03-01

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

  18. Lessons learned during the development and transfer of technology related to a new Hib conjugate vaccine to emerging vaccine manufacturers.

    Science.gov (United States)

    Hamidi, A; Boog, C; Jadhav, S; Kreeftenberg, H

    2014-07-16

    The incidence of Haemophilus Influenzae type b (Hib) disease in developed countries has decreased since the introduction of Hib conjugate vaccines in their National Immunization Programs (NIP). In countries where Hib vaccination is not applied routinely, due to limited availability and high cost of the vaccines, invasive Hib disease is still a cause of mortality. Through the development of a production process for a Hib conjugate vaccine and related quality control tests and the transfer of this technology to emerging vaccine manufacturers in developing countries, a substantial contribution was made to the availability and affordability of Hib conjugate vaccines in these countries. Technology transfer is considered to be one of the fastest ways to get access to the technology needed for the production of vaccines. The first Hib conjugate vaccine based on the transferred technology was licensed in 2007, since then more Hib vaccines based on this technology were licensed. This paper describes the successful development and transfer of Hib conjugate vaccine technology to vaccine manufacturers in India, China and Indonesia. By describing the lessons learned in this process, it is hoped that other technology transfer projects can benefit from the knowledge and experience gained.

  19. Status of vaccine research and development of vaccines for Staphylococcus aureus.

    Science.gov (United States)

    Giersing, Birgitte K; Dastgheyb, Sana S; Modjarrad, Kayvon; Moorthy, Vasee

    2016-06-03

    Staphylococcus aureus is a highly versatile gram positive bacterium that is resident as an asymptomatic colonizer on the skin and in the nasopharynx of approximately 30% of individuals. Nasopharyngeal colonization is a risk for acquiring S. aureus infections, which can cause a range of clinical symptoms that are commonly associated with skin and soft-tissue infections. The emergence of S. aureus strains that are highly resistant to antimicrobials has recently become a major public health concern. In low-income countries the incidence of S. aureus disease is highest in neonates and children up to one year of age and mortality rates are estimated to be up to 50%. In the United States, S. aureus infection accounts for approximately 300,000 hospitalizations per year. A vaccine against multi-drug resistant S. aureus, therefore, is urgently needed. Two vaccine candidates have previously been evaluated in late-stage clinical trials but have not demonstrated efficacy. At present, one vaccine candidate and two monoclonal antibody are undergoing clinical evaluation in target groups at high risk for S. aureus infection. This review provides an overview of current vaccine development efforts and presents the major technical and regulatory challenges to developing a licensed S. aureus vaccine.

  20. Advances in host and vector development for the production of plasmid DNA vaccines.

    Science.gov (United States)

    Mairhofer, Juergen; Lara, Alvaro R

    2014-01-01

    Recent developments in DNA vaccine research provide a new momentum for this rather young and potentially disruptive technology. Gene-based vaccines are capable of eliciting protective immunity in humans to persistent intracellular pathogens, such as HIV, malaria, and tuberculosis, for which the conventional vaccine technologies have failed so far. The recent identification and characterization of genes coding for tumor antigens has stimulated the development of DNA-based antigen-specific cancer vaccines. Although most academic researchers consider the production of reasonable amounts of plasmid DNA (pDNA) for immunological studies relatively easy to solve, problems often arise during this first phase of production. In this chapter we review the current state of the art of pDNA production at small (shake flasks) and mid-scales (lab-scale bioreactor fermentations) and address new trends in vector design and strain engineering. We will guide the reader through the different stages of process design starting from choosing the most appropriate plasmid backbone, choosing the right Escherichia coli (E. coli) strain for production, and cultivation media and scale-up issues. In addition, we will address some points concerning the safety and potency of the produced plasmids, with special focus on producing antibiotic resistance-free plasmids. The main goal of this chapter is to make immunologists aware of the fact that production of the pDNA vaccine has to be performed with as much as attention and care as the rest of their research.

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

    Science.gov (United States)

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

    2015-12-10

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

  2. Moving candidate vaccines into development from research: lessons from HIV.

    Science.gov (United States)

    Sullivan, Mark

    2009-07-01

    There is a logarithmic increase in the cost and complexity of the research and development process when transitioning a promising candidate vaccine from the laboratory into the clinic. Managing complex development programs involving people from diverse technical, cultural and geographical backgrounds is a specialised skill. It is essential that the group is clear on their objectives and how their activities affect others, that communication is open, inclusive and effective, and that the most rigorous, scientific approach based on statistical principles in compliance with regulatory requirements is used. Applying these standards to all vaccine development programs will filter out inappropriate candidates more readily and enhance the efficiency of vaccine development. The challenges of developing a new vaccine are illustrated in human immunodeficiency virus (HIV) vaccinology. Selecting vaccine candidates for HIV requires the ability to evaluate the large number of potential antigens in imperfect and non-standardised animal models. Further, using these models to evaluate questions such as dose scaling to humans, optimal route of administration, the use of adjuvants and potential formulation improvements adds variable to variable, making the interpretation of results particularly challenging. This may lead to the promotion of a poor candidate or the elimination of a good one. The absence of precise immunological correlates of protection and the prohibitive cost of confirmatory clinical trials are further significant barriers. However, there are practical steps that can be taken to standardise early vaccine evaluation, which would result in more efficient development of new vaccines for HIV and other disease areas with similarly challenging development issues (such as hepatitis C virus, influenza, Mycobacterium tuberculosis and malaria).

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    , longevity and functional efficacy compared to corresponding vaccines employing monomeric proteins. The spy-VLP vaccines also effectively broke B cell self-tolerance and induced potent and durable antibody responses upon vaccination with cancer or allergy-associated self-antigens (PD-L1, CTLA-4 and IL-5...

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

    Science.gov (United States)

    Lukashevich, Igor S

    2013-01-01

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

  5. Preventive vaccines for cervical cancer Vacunas para prevenir el cáncer cervical

    OpenAIRE

    Wheeler, Cosette M.

    1997-01-01

    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 guarant...

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

    OpenAIRE

    Veronique Lorenz; Gabriele Karanis; Panagiotis Karanis

    2014-01-01

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

  7. Immunological and Antitumor Effects of IL-23 as a Cancer Vaccine Adjuvant1

    OpenAIRE

    Overwijk, Willem W; Karin E de Visser; Tirion, Felicia H.; de Jong, Laurina A.; Pols, Thijs W. H.; van der Velden, Yme U; Boorn, Jasper G. van den; 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 cytokine, IL-23, in gp100 peptide vaccine therapy of established murine melanoma. Neither systemic nor local IL-23 alone had any impact on tumor growth or tumor-specific T cell numbers. Upon specific va...

  8. Targeted Vaccination against Human α-Lactalbumin for Immunotherapy and Primary Immunoprevention of Triple Negative Breast Cancer

    Directory of Open Access Journals (Sweden)

    Vincent K. Tuohy

    2016-06-01

    Full Text Available We have proposed that safe and effective protection against the development of adult onset cancers may be achieved by vaccination against tissue-specific self-proteins that are “retired” from expression at immunogenic levels in normal tissues as we age, but are overexpressed in emerging tumors. α-Lactalbumin is an example of a “retired” self-protein because its expression in normal tissues is confined exclusively to the breast during late pregnancy and lactation, but is also expressed in the vast majority of human triple negative breast cancers (TNBC—the most aggressive and lethal form of breast cancer and the predominant form that occurs in women at high genetic risk including those with mutated BRCA1 genes. In anticipation of upcoming clinical trials, here we provide preclinical data indicating that α-lactalbumin has the potential as a vaccine target for inducing safe and effective primary immunoprevention as well as immunotherapy against TNBC.

  9. Shigella vaccine development: prospective animal models and current status.

    Science.gov (United States)

    Kim, Yeon-Jeong; Yeo, Sang-Gu; Park, Jae-Hak; Ko, Hyun-Jeong

    2013-01-01

    Shigella was first discovered in 1897 and is a major causative agent of dysenteric diarrhea. The number of affected patients has decreased globally because of improved sanitary conditions; however, Shigella still causes serious problems in many subjects, including young children and the elderly, especially in developing countries. Although antibiotics may be effective, a vaccine would be the most powerful solution to combat shigellosis because of the emergence of drug-resistant strains. However, the development of a vaccine is hampered by several problems. First, there is no suitable animal model that can replace human-based studies for the investigation of the in vivo mechanisms of Shigella vaccines. Mouse, guinea pig, rat, rabbit, and nonhuman primates could be used as models for shigellosis, but they do not represent human shigellosis and each has its own weaknesses. However, a recent murine model based on peritoneal infection with virulent S. flexneri 2a is promising. Moreover, although the inflammatory responses and mechanisms such as pathogenassociated molecular patterns and danger-associated molecular patterns have been studied, the pathology and immunology of Shigella are still not clearly defined. Despite these obstacles, many vaccine candidates have been developed, including live attenuated, killed whole cells, conjugated, and subunit vaccines. The development of Shigella vaccines also demands considerations of the cost, routes of administration, ease of storage (stability), cross-reactivity, safety, and immunogenicity. The main aim of this review is to provide a detailed introduction to the many promising vaccine candidates and animal models currently available, including the newly developed mouse model.

  10. Natural Killer cells as helper cells in Dendritic cell cancer vaccines

    Directory of Open Access Journals (Sweden)

    María Betina Pampena

    2015-01-01

    Full Text Available Vaccine-based cancer immunotherapy has generated highly variable clinical results due to differing methods of vaccine preparation and variation in patient populations, among other lesser factors. Moreover, these clinical responses do not necessarily correspond with the induction of tumor-specific cytotoxic lymphocytes. Here we review the participation of natural killer (NK cells as alternative immune components that could cooperate in successful vaccination treatment. NK cells have been described as helper cells in dendritic cell-based cancer vaccines, but the role in other kinds of vaccination strategies (whole cells, peptide or DNA- based vaccines is poorly understood. In this article we address the following issues regarding the role of NK cells in cancer vaccines: NK cell anti-tumor action sites, and the loci of NK cell interaction with other immune cells; descriptions of new data on the memory characteristics of NK cells described in infectious diseases; and finally phenotypical and functional changes after vaccination measured by immunomonitoring in preclinical and clinical settings.

  11. Vaccines for established cancer: overcoming the challenges posed by immune evasion.

    Science.gov (United States)

    van der Burg, Sjoerd H; Arens, Ramon; Ossendorp, Ferry; van Hall, Thorbald; Melief, Cornelis J M

    2016-04-01

    Therapeutic vaccines preferentially stimulate T cells against tumour-specific epitopes that are created by DNA mutations or oncogenic viruses. In the setting of premalignant disease, carcinoma in situ or minimal residual disease, therapeutic vaccination can be clinically successful as monotherapy; however, in established cancers, therapeutic vaccines will require co-treatments to overcome immune evasion and to become fully effective. In this Review, we discuss the progress that has been made in overcoming immune evasion controlled by tumour cell-intrinsic factors and the tumour microenvironment. We summarize how therapeutic benefit can be maximized in patients with established cancers by improving vaccine design and by using vaccines to increase the effects of standard chemotherapies, to establish and/or maintain tumour-specific T cells that are re-energized by checkpoint blockade and other therapies, and to sustain the antitumour response of adoptively transferred T cells.

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

    NARCIS (Netherlands)

    Blume, S.S.

    2005-01-01

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

  13. Preventing cervical cancer in the United States: barriers and resolutions for HPV vaccination

    Directory of Open Access Journals (Sweden)

    Anna Louise Beavis

    2016-02-01

    Full Text Available HPV vaccination rates for preadolescent and adolescent girls in the United States are far behind those of other developed nations. These rates differ substantially by region and state, socioeconomic status, and insurance status. In parents and young women, a lack of awareness and a misperception of the risk of this vaccine drive low vaccination rates. In physicians, lack of comfort with discussion of sexuality, and the perception that the vaccine should be delayed to a later age contribute to low vaccination rates. Patient and physician-targeted educational campaigns, systems-based interventions, and school-based vaccine clinics offer a variety of ways to address the barriers to HPV vaccination. A diverse and culturally appropriate approach to promoting vaccine uptake has the potential to significantly improve vaccination rates in order to reach the Healthy People 2020 goal of over 80% vaccination in adolescent girls. This article reviews the disparities in HPV vaccination rates in girls in the United States, the influences of patients’, physicians’ and parents’ attitudes on vaccine uptake, and the proposed interventions that may help the US reach its goal for vaccine coverage.

  14. The Capricious Nature of Bacterial Pathogens: Phasevarions and Vaccine Development

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    Aimee Tan

    2016-12-01

    Full Text Available Infectious diseases are a leading cause of morbidity and mortality worldwide, and vaccines are one of the most successful and cost-effective tools for disease prevention. One of the key considerations for rational vaccine development is the selection of appropriate antigens. Antigens must induce a protective immune response, and this response should be directed to stably expressed antigens so the target microbe can always be recognized by the immune system. Antigens with variable expression, due to environmental signals or phase variation (i.e., high frequency, random switching of expression, are not ideal vaccine candidates because variable expression could lead to immune evasion. Phase variation is often mediated by the presence of highly mutagenic simple tandem DNA repeats, and genes containing such sequences can be easily identified, and their use discounted as vaccine antigens reconsidered. Recent research has identified phase variably expressed DNA methyltransferases that act as global epigenetic regulators. These phase variable regulons, known as phasevarions, are associated with altered virulence phenotypes and/or expression of vaccine candidates. As such, genes encoding candidate vaccine antigens that have no obvious mechanism of phase variation may be subject to indirect, epigenetic control as part of a phasevarion. Bioinformatic and experimental studies are required to elucidate the distribution and mechanism of action of these DNA methyltransferases, and most importantly, whether they mediate epigenetic regulation of potential and current vaccine candidates. This process is essential to define the stably expressed antigen target profile of bacterial pathogens and thereby facilitate efficient, rational selection of vaccine antigens.

  15. Development of improved vaccine cell lines against rotavirus

    Science.gov (United States)

    Wu, Weilin; Orr-Burks, Nichole; Karpilow, Jon; Tripp, Ralph A.

    2017-01-01

    Rotavirus is a major cause of severe gastroenteritis among very young children. In developing countries, rotavirus is the major cause of mortality in children under five years old, causing up to 20% of all childhood deaths in countries with high diarrheal disease burden, with more than 90% of these deaths occurring in Africa and Asia. Rotavirus vaccination mimics the first infection without causing illness, thus inducing strong and broad heterotypic immunity against prospective rotavirus infections. Two live vaccines are available, Rotarix and RotaTeq, but vaccination efforts are hampered by high production costs. Here, we present a dataset containing a genome-wide RNA interference (RNAi) screen that identified silencing events that enhanced rotavirus replication. Evaluated against several rotavirus vaccine strains, hits were validated in a Vero vaccine cell line as well as CRISPR/Cas9 generated cells permanently and stably lacking the genes that affect RV replication. Knockout cells were dramatically more permissive to RV replication and permitted an increase in rotavirus replication. These data show a means to improve manufacturing of rotavirus vaccine. PMID:28248921

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

    Science.gov (United States)

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

    2016-10-01

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

  17. Reverse Genetics Approaches for the Development of Influenza Vaccines

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    Aitor Nogales

    2016-12-01

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

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

    Science.gov (United States)

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

    2016-12-20

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

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

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    Mobley, Harry L. T.; Alteri, Christopher J.

    2015-01-01

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

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

    Science.gov (United States)

    Mobley, Harry L T; Alteri, Christopher J

    2015-12-31

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

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

    Directory of Open Access Journals (Sweden)

    Harry L. T. Mobley

    2015-12-01

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

  2. Delivering the promise of the Decade of Vaccines: opportunities and challenges in the development of high quality new vaccines.

    Science.gov (United States)

    Keith, Jacqueline A; Agostini Bigger, Laetitia; Arthur, Phyllis A; Maes, Edith; Daems, Rutger

    2013-04-18

    The Decade of Vaccines (DoV) initiative, launched in 2010, has as its mission "to extend, by 2020 and beyond, the full benefits of immunization to all people, regardless of where they are born, who they are, or where they live". Through their life-saving vaccines, the research-based vaccine companies represented by the International Federation of Pharmaceutical Manufacturers & Associations (IFPMA) and the Biotechnology Industry Organization (BIO) make a major contribution toward this vision. In this article, we begin by summarizing progress made over the past three decades in research and development (R&D) of new and future vaccines, and identify the opportunities and challenges faced by the research-based vaccine industry. We then review the Global Vaccine Action Plan (GVAP) and provide IFPMA and BIO consensus perspectives on its six strategic objectives. Finally, we identify policy measures to support R&D of, and access to, high-quality, innovative vaccines.

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

    Science.gov (United States)

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

    2013-08-01

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

  4. Dengue:epidemiology, prevention and pressing need for vaccine development

    Institute of Scientific and Technical Information of China (English)

    Kuldeep Kumar; Pankaj Kumar Singh; Juhi Tomar; Swati Baijal

    2010-01-01

    Dengue fever is a mosquito born viral infection, and the complicated form of dengue is dengue hemorrhagic fever (DHF). In the recent decades incidence and distribution of dengue has increased dramatically. Dengue viruses belong to family flaviviridae with four serotypes and are transmitted mainly by mosquito Aedes aegypti. Today almost two-fifth of world's population (2.5 million) is at risk of dengue and no specific antiviral drug or vaccine is available against it. Uncontrolled population growth in Africa and South East Asia has increased number of susceptible hosts in urban and semi urban areas. About 40% of world population resides in the high risk area for dengue transmission. According to latest estimates by WHO, yearly 50 to 100 million infections occur globally, this includes around 500 000 DHF and 22 000 deaths, mostly among children. Only symptomatic treatment in the form of analgesic, antipyretics and body fluid management is provided to the patient. Prevention strategies mainly focus on two approaches, firstly on activities to control vector and secondly on activities to protect human from mosquito bite but there is always concerns regarding their sustainably and effectiveness. Theoretically development of an effective dengue vaccine is feasible and production of an effective and affordable vaccine could be a viable option to save humans from this dreadful disease. Conceptually vaccine production is possible, but it has to be tetravalent, providing immunity against all serotypes. Few candidate vaccines are in advance stage of their development; however international cooperation is needed to make these vaccines available on cheaper rates to the poor and vulnerable countries. Objective of this review is to discuss various aspects related to dengue, its epidemiology, available preventive methods, need for vaccine and challenges in its development.

  5. Vaccine Development for Biothreat Alpha Viruses

    Science.gov (United States)

    2011-09-25

    virus (IV) BeAr35645 Cassabou virus (V) Rio Negro virus (VI) EEEV EEEV NA Lineage I FL93-939 EEEV SA Lineage II-IV BeAr436087 WEEV WEEV CBA87 WEEV ON41...Bioterr Biodef ISSN:2157-2526 JBTBD an open access journal 17. Fauquet CM, Mayo MA, Maniloff J, Desselberger U, Ball LA (2005) Virus Taxonomy:Eighth...vaccinated with chimeric SIN/VEE viruses. J Virol 80: 2784-2796. 33. Atasheva S, Wang E, Adams AP, Plante KS, Ni S, et al. (2009) Chimeric alphavirus

  6. Gradual reduction of testosterone using a gonadotropin-releasing hormone vaccination delays castration resistance in a prostate cancer model

    Science.gov (United States)

    Barranco, Jesús A. Junco; Millar, Robert P.; Fuentes, Franklin; Bover, Eddy; Pimentel, Eulogio; Basulto, Roberto; Calzada, Lesvia; Morán, Rolando; Rodríguez, Ayni; Garay, Hilda; Reyes, Osvaldo; Castro, Maria D.; Bringas, Ricardo; Arteaga, Niurka; Toudurí, Henio; Rabassa, Mauricio; Fernández, Yairis; Serradelo, Andrés; Hernández, Eduardo; Guillén, Gerardo E.

    2016-01-01

    In a previous study aimed to design a novel prostate cancer vaccine, the authors of the present study demonstrated the advantage of combining the adjuvants Montanide ISA 51 with very small size proteoliposomes (VSSP) to promote a significant humoral immune response to gonadotropin-releasing hormone (GnRH) in healthy animals. The present study compared the efficacy of this vaccine formulation versus the standard treatment currently available in terms of preventing the development of tumors in DD/S mice injected with Shionogi carcinoma (SC) 115 cells. The results demonstrated that 5 non-vaccinated control mice exhibited a fast tumor growth, and succumbed to the disease within 19–31 days. Mice immunized with the GnRH/Montanide ISA 51/VSSP vaccine exhibited a moderate decline in testosterone levels that was associated with a decrease in anti-GnRH antibody titers, which lead to a sustained tumor growth inhibition. In total, 2 mice in the immunized group exhibited complete remission of the tumor for the duration of the present study. In addition, castrated mice, which were used as a control for standard hormonal therapy, exhibited an accelerated decrease in tumor size. However, tumor relapse was observed between days 50 and 54, and between days 65 and 85, following the injection of SC 155 cells. Therefore, these mice were sacrificed at day 90. The present study concludes that the slow and moderate reduction of testosterone levels observed using the GnRH-based vaccine may delay the appearance of castration resistance in a Shionogi prostate cancer model. These findings suggest that this vaccine may be used to delay castration resistance in patients with prostate cancer. PMID:27446378

  7. Development of cancer immunotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Yun, Yeon Sook; Chung, H. Y.; Yi, S. Y.; Kim, K. W.; Kim, B. K.; Chung, I. S.; Park, J. Y

    1999-04-01

    To increase the curative rate of cancer patients, we developed ideal biological response modifier from medicinal plants: Ginsan, KC68IId-8, KC-8Ala, KG-30. Ginsan activated natural killer cell activity of spleen cells more than 5.4 times than lentinan, 1.4 times than picibanil. Radioprotective activity of Ginsan is stronger than WR2721, glucan, and selenium. The immunogenicity of MOPC tumor cells was augmented by treatment with IL-10 antisense oligonucleotide and by transfection with VEGF sense-, antisense gene. The immunogenicity of MOPC tumor cells was augmented by treatment with IL-10 antisense oligonucleotide and by transfection with VEGF sense-, antisense gene. The immunogenicity of A20 tumor cells was also augmented by transfection with B7.1 gene. The immunosuppression of gamma-irradiation was due to the reduction of Th1 sytokine gene expression through STAT pathway. These research will devote to develop new cancer immunotherapy and to reduce side effect of cancer radiotherapy and chemotherapy.

  8. 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.

  9. Exploiting the immunogenic potential of cancer cells for improved dendritic cell vaccines

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    Lien eVandenberk

    2016-01-01

    Full Text Available Cancer immunotherapy is currently the hottest topic in the oncology field, owing predominantly to the discovery of immune checkpoint blockers. These promising antibodies and their attractive combinatorial features have initiated the revival of other effective immunotherapies like dendritic cell (DC vaccinations. Although DC-based immunotherapy can induce objective clinical and immunological responses in several tumor types, the immunogenic potential of this monotherapy is still considered suboptimal. Hence, focus should be directed on potentiating its immunogenicity by making step-by-step protocol innovations to obtain next-generation Th1-driving DC vaccines. We review some of the latest developments in the DC vaccination field, with a special emphasis on strategies that are applied to obtain a highly immunogenic tumor cell cargo to load and to activate the DCs. To this end, we discuss the effects of three immunogenic treatment modalities (ultraviolet light, oxidizing treatments and heat shock and five potent inducers of immunogenic cell death (radiotherapy, shikonin, high-hydrostatic pressure, oncolytic viruses and (hypericin-based photodynamic therapy on DC biology and their application in DC-based immunotherapy in preclinical as well as clinical settings.

  10. 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.

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

    Science.gov (United States)

    Clemens, John

    2011-10-12

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

  12. Hepatitis B vaccine in developing countries: problems and prospects.

    Science.gov (United States)

    Ayoola, E A

    1984-01-01

    Hepatitis B vaccines are highly immunogenic. To determine the efficacy of low doses and of the intradermal route of vaccination, 197 Nigerian children were given 3 monthly doses of Hevac B. Of these, 96 had 2 micrograms subcutaneously and 101 had 2 micrograms intradermally. One month after completing the schedule, 82.3% and 74.3% of the respective groups had become anti-HBs positive without adverse side-effects. In the second part of the study, 50 chronic HBsAg carriers were vaccinated. Compared to placebo-treated carriers, no effect was demonstrated with regard to HBsAg clearance or anti-HBs production. Immune complexes were not attributable to Hevac B. No untoward effects were noted. Booster vaccination of 50 initial non-responders resulted in the development of significant levels of anti-HBs in 20 (40%) of the recipients. None of the 'non-responders' developed clinical or virological evidence of HBV infection. It is concluded that low-dose vaccination is effective and that the intradermal route may be useful in developing countries.

  13. Experimental animal modelling for TB vaccine development

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    Pere-Joan Cardona

    2017-03-01

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

  14. Immunotherapy and lung cancer: current developments and novel targeted therapies.

    Science.gov (United States)

    Domingues, Duarte; Turner, Alice; Silva, Maria Dília; Marques, Dânia Sofia; Mellidez, Juan Carlos; Wannesson, Luciano; Mountzios, Giannis; de Mello, Ramon Andrade

    2014-01-01

    Non-small-cell lung cancer (NSCLC) is a highly prevalent and aggressive disease. In the metastatic setting, major advances include the incorporation of immunotherapy and targeted therapies into the clinician's therapeutic armamentarium. Standard chemotherapeutic regimens have long been reported to interfere with the immune response to the tumor; conversely, antitumor immunity may add to the effects of those therapies. The aim of immunotherapy is to specifically enhance the immune response directed to the tumor. Recently, many trials addressed the role of such therapies for metastatic NSCLC treatment: ipilimumab, tremelimumab, nivolumab and lambrolizumab are immunotherapeutic agents of main interest in this field. In addition, anti-tumor vaccines, such as MAGE-A3, Tecetomide, TG4010, CIMAvax, ganglioside vaccines, tumor cell vaccines and dendritic cell vaccines, emerged as potent inducers of immune response against the tumor. The current work aims to address the most recent developments regarding these innovative immunotherapies and their implementation in the treatment of metastatic NSCLC.

  15. Vaccines for the prevention of dengue: development update.

    Science.gov (United States)

    Thomas, Stephen J; Endy, Timothy P

    2011-06-01

    The dengue viruses (DENV) are mosquito-borne flaviviruses which cause a spectrum of clinical disease known as "dengue," and have emerged and re-emerged as a significant global health problem. It is estimated more than 120 countries currently have endemic DENV transmission, 55% of the world's population is at risk of infection, and there are between 70-500 million infections of which 2.1 million are clinically severe resulting in 21,000 deaths annually. By all estimates the global dengue problem will continue to worsen due to the increasing mobility of the population, ecological changes, and the inability to effectively sustain vector control. There are no licensed antivirals or vaccines to treat or prevent dengue. The development and widespread use of a safe and efficacious dengue vaccine is required to significantly reduce the global dengue burden. In this review the authors discuss dengue vaccines currently in the pre-clinical and clinical development pipeline.

  16. Development of Mucosal Vaccines Based on Lactic Acid Bacteria

    Science.gov (United States)

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

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

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

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    Mayu O Frank

    Full Text Available BACKGROUND: 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. METHODS AND FINDINGS: 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. CONCLUSIONS: An apoptotic cancer cell vaccine modeled on naturally occurring tumor immune responses in PND patients provides a safe and immunogenic tumor vaccine. TRIAL REGISTRATION: ClinicalTrials.gov NCT00289341.

  18. A prospective highlight on exosomal nanoshuttles and cancer immunotherapy and vaccination

    Directory of Open Access Journals (Sweden)

    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.

  19. Chicken HSP70 DNA vaccine inhibits tumor growth in a canine cancer model.

    Science.gov (United States)

    Yu, Wen-Ying; Chuang, Tien-Fu; Guichard, Cécile; El-Garch, Hanane; Tierny, Dominique; Laio, Albert Taiching; Lin, Ching-Si; Chiou, Kuo-Hao; Tsai, Cheng-Long; Liu, Chen-Hsuan; Li, Wen-Chiuan; Fischer, Laurent; Chu, Rea-Min

    2011-04-18

    Immunization with xenogeneic DNA is a promising cancer treatment to overcome tolerance to self-antigens. Heat shock protein 70 (HSP70) is over-expressed in various kinds of tumors and is believed to be involved in tumor progression. This study tested a xenogeneic chicken HSP70 (chHSP70) DNA vaccine in an experimental canine transmissible venereal tumor (CTVT) model. Three vaccination strategies were compared: the first (PE) was designed to evaluate the prophylactic efficacy of chHSP70 DNA vaccination by delivering the vaccine before tumor inoculation in a prime boost setting, the second (T) was designed to evaluate the therapeutic efficacy of the same prime boost vaccine by vaccinating the dogs after tumor inoculation; the third (PT) was similar to the first strategy (PE), with the exception that the electroporation booster injection was replaced with a transdermal needle-free injection. Tumor growth was notably inhibited only in the PE dogs, in which the vaccination program triggered tumor regression significantly sooner than in control dogs (NT). The CD4(+) subpopulation of tumor-infiltrating lymphocytes and canine HSP70 (caHSP70)-specific IFN-γ-secreting lymphocytes were significantly increased during tumor regression in the PE dogs as compared to control dogs, demonstrating that specific tolerance to caHSP70 has been overcome. In contrast, no benefit of the therapeutic strategy (T) could be noticed and the (PT) strategy only led to partial control of tumor growth. In summary, antitumor prophylactic activity was demonstrated using the chHSP70 DNA vaccine including a boost via electroporation. Our data stressed the importance of DNA electroporation as a booster to get the full benefit of DNA vaccination but also of cancer immunotherapy initiation as early as possible. Xenogeneic chHSP70 DNA vaccination including an electroporation boost is a potential vaccine to HSP70-expressing tumors, although further research is still required to better understand true

  20. Tumor antigens for cancer immunotherapy: therapeutic potential of xenogeneic DNA vaccines

    Directory of Open Access Journals (Sweden)

    Srinivasan Roopa

    2004-04-01

    Full Text Available Abstract Preclinical animal studies have convincingly demonstrated that tumor immunity to self antigens can be actively induced and can translate into an effective anti-tumor response. Several of these observations are being tested in clinical trials. Immunization with xenogeneic DNA is an attractive approach to treat cancer since it generates T cell and antibody responses. When working in concert, these mechanisms may improve the efficacy of vaccines. The use of xenogeneic DNA in overcoming immune tolerance has been promising not only in inbred mice with transplanted tumors but also in outbred canines, which present with spontaneous tumors, as in the case of human. Use of this strategy also overcomes limitations seen in other types of cancer vaccines. Immunization against defined tumor antigens using a xenogeneic DNA vaccine is currently being tested in early phase clinical trials for the treatment of melanoma and prostate cancers, with proposed trials for breast cancer and Non-Hodgkin's Lymphoma.

  1. Immune adjuvants as critical guides directing immunity triggered by therapeutic cancer vaccines.

    Science.gov (United States)

    Schijns, Virgil; Tartour, Eric; Michalek, Jaroslav; Stathopoulos, Apostolos; Dobrovolskienė, Neringa T; Strioga, Marius M

    2014-04-01

    Tumor growth is controlled by natural antitumor immune responses alone or by augmented immune reactivity resulting from different forms of immunotherapy, which has demonstrated clinical benefit in numerous studies, although the overall percentage of patients with durable clinical responses remains limited. This is attributed to the heterogeneity of the disease, the inclusion of late-stage patients with no other treatment options and advanced tumor-associated immunosuppression, which may be consolidated by certain types of chemotherapy. Despite variable responsiveness to distinct types of immunotherapy, therapeutic cancer vaccination has shown meaningful efficacy for a variety of cancers. A key step during cancer vaccination involves the appropriate modeling of the functional state of dendritic cells (DCs) capable of co-delivering four critical signals for proper instruction of tumor antigen-specific T cells. However, the education of DCs, either directly in situ, or ex vivo by various complex procedures, lacks standardization. Also, it is questioned whether ex vivo-prepared DC vaccines are superior to in situ-administered adjuvant-guided vaccines, although both approaches have shown success. Evaluation of these variables is further complicated by a lack of consensus in evaluating vaccination clinical study end points. We discuss the role of signals needed for the preparation of classic in situ and modern ex vivo DC vaccines capable of proper reprogramming of antitumor immune responses in patients with cancer.

  2. Development and technology transfer of Haemophilus influenzae type b conjugate vaccines for developing countries.

    Science.gov (United States)

    Beurret, Michel; Hamidi, Ahd; Kreeftenberg, Hans

    2012-07-13

    This paper describes the development of a Haemophilus influenzae type b (Hib) conjugate vaccine at the National Institute for Public Health and the Environment/Netherlands Vaccine Institute (RIVM/NVI, Bilthoven, The Netherlands), and the subsequent transfer of its production process to manufacturers in developing countries. In 1998, at the outset of the project, the majority of the world's children were not immunized against Hib because of the high price and limited supply of the conjugate vaccines, due partly to the fact that local manufacturers in developing countries did not master the Hib conjugate production technology. To address this problem, the RIVM/NVI has developed a robust Hib conjugate vaccine production process based on a proven model, and transferred this technology to several partners in India, Indonesia, Korea and China. As a result, emerging manufacturers in developing countries acquired modern technologies previously unavailable to them. This has in turn facilitated their approach to producing other conjugate vaccines. As an additional spin-off from the project, a World Health Organization (WHO) Hib quality control (QC) course was designed and conducted at the RIVM/NVI, resulting in an increased regulatory capacity for conjugate vaccines in developing countries at the National Regulatory Authority (NRA) level. For the local populations, this has translated into an increased and sustainable supply of affordable Hib conjugate-containing combination vaccines. During the course of this project, developing countries have demonstrated their ability to produce large quantities of high-quality modern vaccines after a successful transfer of the technology.

  3. The granulocyte macrophage–colony stimulating factor surface modified MB49 bladder cancer stem cells vaccine against metastatic bladder cancer

    Directory of Open Access Journals (Sweden)

    Yong-tong Zhu

    2014-07-01

    Full Text Available The MB49 bladder cancer cell vaccine was effective against bladder cancer in the mice model in previous studies. However, part of the tumors regrew as the vaccine could not eliminate the cancer stem cells (CSCs. MB49 bladder cancer stem cells (MCSCs were isolated by a combination of the limited dilution method and the serum free culture medium method. MCSCs possessed higher expression of CD133, CD44, OCT4, NANOG, and ABCG2, the ability of differentiation, higher proliferative abilities, lower susceptibility to chemotherapy, greater migration in vitro, and stronger tumorigenic abilities in vivo. Then streptavidin–mouse granulocyte macrophage–colony stimulating factor (SA–mGM–CSF MCSCs vaccine was prepared. SA–mGM–CSF MCSCs vaccine extended the survival of the mice and inhibited the growth of tumor in protective, therapeutic, memorial and specific immune response experiments. The level of immunoglobulin G and the ratio of dendritic cells and CD4+ and CD8+ T cells were highest in the experimental group when compared to those in other four control groups, as well as for the cytotoxicity assay. We demonstrated that SA–mGM–CSF MCSCs vaccine induces an antitumor immune response to metastatic bladder cancer.

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

    Science.gov (United States)

    Riddle, Mark S; Guerry, Patricia

    2016-06-03

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

  5. Clinical development of placental malaria vaccines and immunoassays harmonization

    DEFF Research Database (Denmark)

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

    2016-01-01

    Placental malaria caused by Plasmodium falciparum infection constitutes a major health problem manifesting as severe disease and anaemia in the mother, impaired fetal development, low birth weight or spontaneous abortion. Prevention of placental malaria currently relies on two key strategies...... that are losing efficacy due to spread of resistance: long-lasting insecticide-treated nets and intermittent preventive treatment during pregnancy. A placental malaria vaccine would be an attractive, cost-effective complement to the existing control tools. Two placental malaria vaccine candidates are currently...

  6. The future for vaccine development against Entamoeba histolytica.

    Science.gov (United States)

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

    2014-01-01

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

  7. No acquisition: a new ambition for HIV vaccine development?

    Science.gov (United States)

    Lakhashe, Samir K; Silvestri, Guido; Ruprecht, Ruth M

    2011-10-01

    Development of a safe and effective prophylactic HIV-1 vaccine presents unique challenges. The pessimism following the failure of two HIV-1 vaccine concepts in clinical trials, HIV-1 gp120 and an adenovirus-based approach to induce only cellular immune responses, has been replaced by cautious optimism engendered by the RV144 trial outcome, the isolation of several new broadly reactive neutralizing monoclonal antibodies, and recent primate model data indicating prevention of viral acquisition by active or passive immunization. Intense efforts are underway to optimize immunogen design, adjuvants, and the tools for preclinical evaluation of candidate vaccines in primates, where correlates of protection can be examined in detail - as proof-of-concept for clinical trials.

  8. Trials and tribulations on the path to developing a dengue vaccine.

    Science.gov (United States)

    Thomas, Stephen J; Rothman, Alan L

    2015-11-27

    Dengue is a rapidly expanding global health problem. Development of a safe and efficacious tetravalent vaccine along with strategic application of vector control activities represents a promising approach to reducing the global disease burden. Although many vaccine development challenges exist, numerous candidates are in clinical development and one has been tested in three clinical endpoint studies. The results of these studies have raised numerous questions about how we measure vaccine immunogenicity and how these readouts are associated with clinical outcomes in vaccine recipients who experience natural infection. In this review the authors discuss the dengue vaccine pipeline, development challenges, the dengue vaccine-immunologic profiling intersection, and research gaps.

  9. The Immune Space: A Concept and Template for Rationalizing Vaccine Development

    OpenAIRE

    Manrique, Amapola; Adams, Elizabeth; Barouch, Dan H.; Fast, Pat; Graham, Barney S; Kim, Jerome H.; Kublin, James G.; McCluskey, Margaret; Pantaleo, Giuseppe; Robinson, Harriet L.; Russell, Nina; Snow, William; Margaret I Johnston

    2014-01-01

    Empirical testing of candidate vaccines has led to the successful development of a number of lifesaving vaccines. The advent of new tools to manipulate antigens and new methods and vectors for vaccine delivery has led to a veritable explosion of potential vaccine designs. As a result, selection of candidate vaccines suitable for large-scale efficacy testing has become more challenging. This is especially true for diseases such as dengue, HIV, and tuberculosis where there is no validated anima...

  10. HPV infection in cervical and other cancers in Saudi Arabia: implication for prevention and vaccination

    Directory of Open Access Journals (Sweden)

    Ghazi eAlsbeih

    2014-03-01

    Full Text Available HPV is closely associated with cervical cancer that the incidence of this tumor is regarded as a surrogate marker for HPV infection in countries lacking epidemiological studies. HPV is also implicated in subsets of anogenital and oro-pharyngeal cancers. Although cervical cancer is the third most common cancer in women worldwide, its reported incidence is low in Saudi Arabia, ranking number 12 between all cancers in females and accounts only for 2.4% of all new cases, despite the lack of national screening programs. However, the limited available studies from Saudi Arabia indicate that HPV prevalence and genotypes’ distribution in invasive cervical cancer show similar pattern as in the world. Cytology screening (Pap Smear and HPV vaccinations are the two preventive measures against cervical cancer. The two available vaccines are effective against the two most common HPV genotypes (HPV-16 and 18. Since 92% of cervical tumors in the Kingdom are infected with HPV of which 78% are HPV-16 and 18 genotypes, vaccination is expected to protect against more than two-third of cervical cancers in Saudi Arabia. Nevertheless, due to its low incidence (2.1/100,000 women, a proper cost-effectiveness analysis is required to justify the implementation of a costly vaccine bearing in mind that HPV could potentially be associated with about 3% of all cancers. However, further studies are needed to ascertain the real prevalence of HPV at the population level at large, its association with various types of cancers and also the impact of local tradition and emerging behavioral trends that could affect HPV transmission and consequently the effectiveness of applying national vaccination program.

  11. Live bacterial delivery systems for development of mucosal vaccines

    NARCIS (Netherlands)

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

    2000-01-01

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

  12. Biotechnology in the diagnosis of infectious diseases and vaccine development

    Science.gov (United States)

    Molecular biological methods have become increasingly applicable to the diagnosis of infectious diseases and vaccine development. To become widely used the methods need to be easy, safe, sensitive, reproducible and eventually automated to facilitate the evaluation of large number of samples. The p...

  13. Development of lactococcal GEM-based pneumococcal vaccines

    NARCIS (Netherlands)

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

    2007-01-01

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

  14. Development of lactococcal GEM-based pneumococcal vaccines.

    NARCIS (Netherlands)

    Audouy, S.A.; Selm, S. van; Roosmalen, M.L. van; Post, E.; Kanninga, R.; Neef, J.; Estevao, S.; Nieuwenhuis, E.E.; Adrian, P.V.; Leenhouts, K.; Hermans, P.W.M.

    2007-01-01

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

  15. Economic evaluations of hepatitis B vaccination for developing countries

    NARCIS (Netherlands)

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

    2009-01-01

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

  16. Knowledge and acceptability of human papillomavirus vaccination and cervical cancer screening among women in Karnataka, India.

    Science.gov (United States)

    Montgomery, Martha P; Dune, Tanaka; Shetty, Prasanna K; Shetty, Avinash K

    2015-03-01

    Cervical cancer is the leading cause of cancer-related mortality among women in India; however, participation in prevention and screening is low and the reasons for this are not well understood. In a cross-sectional survey in August 2008, 202 healthy women in Karnataka, India completed a questionnaire regarding knowledge, attitudes, and practices related to human papillomavirus (HPV) and cervical cancer. Factors associated with vaccination and Papanicolau (Pap) smear screening acceptance were explored. Thirty-six percent of women had heard of HPV while 15% had heard of cervical cancer. Five percent of women reported ever having a Pap smear, and 4% of women felt at risk of HPV infection. Forty-six percent of women were accepting of vaccination, but fewer (21%) were willing to have a Pap smear. Overall, knowledge related to HPV and cervical cancer topics was low. Women with negative attitudes toward HPV infection were 5.3 (95% confidence interval (CI) 2.8-10) times more likely to accept vaccination but were not significantly more likely to accept Pap smear (odds ratio 1.5, 95% CI 0.7-3.0). Cost and a low level of perceived risk were the most frequent factors cited as potential barriers. Improving awareness of HPV and cervical cancer through health care providers in addition to increasing access to vaccination and screening through government-sponsored programs may be feasible and effective methods to reduce cervical cancer burden in India.

  17. Vaccinia Virus: A Tool for Research and Vaccine Development

    Science.gov (United States)

    Moss, Bernard

    1991-06-01

    Vaccinia virus is no longer needed for smallpox immunization, but now serves as a useful vector for expressing genes within the cytoplasm of eukaryotic cells. As a research tool, recombinant vaccinia viruses are used to synthesize biologically active proteins and analyze structure-function relations, determine the targets of humoral- and cell-mediated immunity, and investigate the immune responses needed for protection against specific infectious diseases. When more data on safety and efficacy are available, recombinant vaccinia and related poxviruses may be candidates for live vaccines and for cancer immunotherapy.

  18. Gonadotrophin releasing hormone-based vaccine, an effective candidate for prostate cancer and other hormone-sensitive neoplasms.

    Science.gov (United States)

    Junco, Jesús A; Basalto, Roberto; Fuentes, Franklin; Bover, Eddy; Reyes, Osvaldo; Pimentel, Eulogio; Calzada, Lesvia; Castro, Maria D; Arteaga, Niurka; López, Yovisleidis; Hernández, Héctor; Bringas, Ricardo; Garay, Hilda; Peschke, Peter; Bertot, José; Guillén, Gerardo

    2008-01-01

    Prostate growth, development, functions, and neoplastic transformation is androgen dependent. Estrogens have similar effects in the ovary and breast. Previous studies using gonadotrophin releasing hormone (GnRH/LHRH) vaccines have shown the usefulness of immunization against this hormone in prostate (PC) and breast cancer (BC). We have synthesized a peptide mutated at position 6 and attached to the 830-844 tetanic toxoid (TT) helper T cell sequence in the same synthesis process. After repeated pig immunizations, we have demonstrated a vaccine that significantly decreased testes size (p < 0.001), prostate (p < 0.01), seminal vesicles (p < 0.01), and testosterone (T) castration [0.05 nM ml(-1) (p < 0. 01)]. Similar results were obtained in adult male and female healthy dogs and Macaca fascicularis models. These data indicate that this GnRHm1-TT vaccine is safe and able to induce significant tumor growth inhibition in the Dunning R3327-H rat androgen responsive prostate tumor model. In these rats, the immunization induced high anti-GnRH titers concomitant with T castration reduction (p < 0.01) in 90% of the animals tested. In addition, 70% of the responders exhibited tumor growth inhibition (p = 0.02) and a survival rate approximately three times longer that those of untreated rats. These data indicate that GnRHm1-TT vaccine may be a potential candidate in the treatment of PC, BC, and other hormone-dependent cancers.

  19. 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...... 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......-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....

  20. 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......-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...

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

    Science.gov (United States)

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

    2015-01-01

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

  2. A feasibility study of cyclophosphamide, trastuzumab, and an allogeneic GM-CSF-secreting breast tumor vaccine for HER2+ metastatic breast cancer.

    Science.gov (United States)

    Chen, Gang; Gupta, Richa; Petrik, Silvia; Laiko, Marina; Leatherman, James M; Asquith, Justin M; Daphtary, Maithili M; Garrett-Mayer, Elizabeth; Davidson, Nancy E; Hirt, Kellie; Berg, Maureen; Uram, Jennifer N; Dauses, Tianna; Fetting, John; Duus, Elizabeth M; Atay-Rosenthal, Saadet; Ye, Xiaobu; Wolff, Antonio C; Stearns, Vered; Jaffee, Elizabeth M; Emens, Leisha A

    2014-10-01

    Granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting tumor vaccines are bioactive, but limited by disease burden and immune tolerance. Cyclophosphamide augments vaccine activity in tolerant neu mice and in patients with metastatic breast cancer. HER2-specific monoclonal antibodies (mAb) enhance vaccine activity in neu mice. We hypothesized that cyclophosphamide-modulated vaccination with HER2-specific mAb safely induces relevant HER2-specific immunity in neu mice and patients with HER2+ metastatic breast cancer. Adding both cyclophosphamide and the HER2-specific mAb 7.16.4 to vaccination maximized HER2-specific CD8+ T-cell immunity and tumor-free survival in neu transgenic mice. We, therefore, conducted a single-arm feasibility study of cyclophosphamide, an allogeneic HER2+ GM-CSF-secreting breast tumor vaccine, and weekly trastuzumab in 20 patients with HER2+ metastatic breast cancer. Primary clinical trial objectives were safety and clinical benefit, in which clinical benefit represents complete response + partial response + stable disease. Secondary study objectives were to assess HER2-specific T-cell responses by delayed type hypersensitivity (DTH) and intracellular cytokine staining. Patients received three monthly vaccinations, with a boost 6 to 8 months from trial entry. This combination immunotherapy was safe, with clinical benefit rates at 6 months and 1 year of 55% [95% confidence interval (CI), 32%-77%; P = 0.013] and 40% (95% CI, 19%-64%), respectively. Median progression-free survival and overall survival durations were 7 months (95% CI, 4-16) and 42 months (95% CI, 22-70), respectively. Increased HER2-specific DTH developed in 7 of 20 patients [of whom 4 had clinical benefit (95% CI, 18-90)], with a trend toward longer progression-free survival and overall survival in DTH responders. Polyfunctional HER2-specific CD8+ T cells progressively expanded across vaccination cycles. Further investigation of cyclophosphamide-modulated vaccination

  3. Human papillomavirus vaccination: the policy debate over the prevention of cervical cancer--a commentary.

    Science.gov (United States)

    Hoops, Katherine E M; Twiggs, Leo B

    2008-07-01

    The human papillomavirus (HPV) family causes a variety of benign, premalignant, and malignant lesions in men and women. HPV types 16 and 18 are responsible for causing 70% of all cases of cervical cancer each year. Recently, a vaccine that can prevent cervical cancer by protecting women from infection with the most common types of HPV has been made available. Following Food and Drug Administration approval and endorsement by the Centers for Disease Control and Prevention, it is the right and the duty of the state legislatures to implement vaccination programs. This vaccine, a vaccine for a sexually transmitted disease, has stirred a fierce debate. Religion and sexuality have dominated the discussion, and political calculations are inherent to the process; nonetheless, epidemiological analyses are also essential to the decision to mandate the HPV vaccine. HPV vaccine program implementation processes are at many stages in many states, and programs vary widely. Some provide information to families, whereas others allot a range of funding for voluntary vaccination. Virginia is, thus far, the only state to have enacted a mandate. This article discusses the various programs in place, the proposed legislation, and the debate surrounding the political process.

  4. Transcription factor Fos-related antigen 1 is an effective target for a breast cancer vaccine

    Science.gov (United States)

    Luo, Yunping; Zhou, He; Mizutani, Masato; Mizutani, Noriko; Reisfeld, Ralph A.; Xiang, Rong

    2003-07-01

    Protection against breast cancer was achieved with a DNA vaccine against murine transcription factor Fos-related antigen 1, which is overexpressed in aggressively proliferating D2F2 murine breast carcinoma. Growth of primary s.c. tumor and dissemination of pulmonary metastases was markedly suppressed by this oral DNA vaccine, carried by attenuated Salmonella typhimurium, encoding murine Fos-related antigen 1, fused with mutant polyubiquitin, and cotransformed with secretory murine IL-18. The life span of 60% of vaccinated mice was tripled in the absence of detectable tumor growth after lethal tumor cell challenge. Immunological mechanisms involved activation of T, natural killer, and dendritic cells, as indicated by up-regulation of their activation markers and costimulatory molecules. Markedly increased specific target cell lysis was mediated by both MHC class I-restricted CD8+ T cells and natural killer cells isolated from splenocytes of vaccinated mice, including a significant release of proinflammatory cytokines IFN- and IL-2. Importantly, fluorescence analysis of fibroblast growth factor 2 and tumor cell-induced vessel growth in Matrigel plugs demonstrated marked suppression of angiogenesis only in vaccinated animals. Taken together, this multifunctional DNA vaccine proved effective in protecting against growth and metastases of breast cancer by combining the action of immune effector cells with suppression of tumor angiogenesis. vaccine | tumor | metastases | antiangiogenesis

  5. Human papillomavirus related cervical cancer and anticipated vaccination challenges in Ethiopia.

    Science.gov (United States)

    Gebremariam, TeweldeTesfaye

    2016-01-01

    Cervical cancer is the leading cause of cancer deaths among women in Ethiopia. This may be due to the high prevalence of high-risk human papillomavirus (HR-HPV) genotypes in the population. So far, few studies have been done that showed the presence of HR-HPV genotypes. The HR-HPV-16, -18, -52, -56, -31 and -58 were the most common genotypes reported in Ethiopia. The introduction of HPV vaccines in Ethiopia is likely to go a long way in reducing cervical cancer deaths. However, there are few challenges to the introduction of the vaccines. The target population for HPV vaccination is at the moment not well-defined. Besides, the current HPV vaccines confer only type-specific (HPV-16 and -18) immunity, leaving a small proportion of Ethiopian women unprotected against other HR-HPV genotypes such as 52, 56, 31 and 58. Thus, future HPV vaccines such as the nanovalent vaccine may be more useful to Ethiopia as they will protect women against more genotypes.

  6. 76 FR 69743 - The Development and Evaluation of Human Cytomegalovirus Vaccines; Public Workshop

    Science.gov (United States)

    2011-11-09

    ... Development and Evaluation of Human Cytomegalovirus Vaccines.'' The purpose of the public workshop is to... related to vaccine development. Date and Time: The public workshop will be held on January 10 and January... biology and epidemiology and on vaccine development strategies. Topics for discussion will include:...

  7. [Overview of the Ebola vaccines in pre-clinical and clinical development].

    Science.gov (United States)

    Buchy, P

    2016-10-01

    The Ebola epidemic that occurred in West Africa between 2013-2016 significantly accelerated the research and development of Ebola vaccines. Few dozens of clinical trials have been recently conducted leading to opportunities to test several new vaccine candidates. Other vaccines are still in early development phases (table 1). This paper provides an overview of the new developments in that area.

  8. 76 FR 49776 - The Development and Evaluation of Next-Generation Smallpox Vaccines; Public Workshop

    Science.gov (United States)

    2011-08-11

    ... workshop entitled ``The Development and Evaluation of Next-Generation Smallpox Vaccines.'' The purpose of... response to smallpox vaccines and development of animal models for demonstration of effectiveness of next... under development do not produce the characteristic ``vaccine take.'' In addition, it is not ethical...

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

    Science.gov (United States)

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

    2017-01-01

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

  10. 宫颈癌治疗性疫苗研究进展%Advances in the research of therapeutic vaccines against cervical cancer

    Institute of Scientific and Technical Information of China (English)

    邓玲; 刘金辉; 施桥发

    2010-01-01

    宫颈癌为妇女最常见的恶性肿瘤之一,其与人乳头瘤病毒(human papillomavirus,HPV)感染密切相关.随着对HPV及其致病机理研究的深入和免疫学的发展,利用免疫学方法治疗HPV引发的疾病显示良好的前景.目前,有关HPV治疗性疫苗的研究已取得较大进展,这些疫苗包括病毒/细菌载体疫苗、肽疫苗、蛋白疫苗、DNA疫苗、细胞疫苗等.此文就HPV治疗性疫苗的研究进展做一综述.%Cervical cancer, one of the most common cancers in women, is closely associated with human papillomavirus (HPV) infection.Along with development of immunology as well as study on HPV and its pathogenic mechanism, the treatment of HPV-related diseases by immunological methods has showed excellent prospect.Great advances in therapeutic vaccines-including viral and bacterial vector vaccines, peptide and protein vaccines, nucleic acid or DNA vaccines, and cell-based vaccines- against cervical cancer have been achieved in recent years.The progress in study on therapeutic vaccines against HPV is reviewed in this paper.

  11. Nanoparticle Drug Delivery Systems Designed to Improve Cancer Vaccines and Immunotherapy.

    Science.gov (United States)

    Fan, Yuchen; Moon, James J

    2015-01-01

    Recent studies have demonstrated great therapeutic potential of educating and unleashing our own immune system for cancer treatment. However, there are still major challenges in cancer immunotherapy, including poor immunogenicity of cancer vaccines, off-target side effects of immunotherapeutics, as well as suboptimal outcomes of adoptive T cell transfer-based therapies. Nanomaterials with defined physico-biochemical properties are versatile drug delivery platforms that may address these key technical challenges facing cancer vaccines and immunotherapy. Nanoparticle systems have been shown to improve targeted delivery of tumor antigens and therapeutics against immune checkpoint molecules, amplify immune activation via the use of new stimuli-responsive or immunostimulatory materials, and augment the efficacy of adoptive cell therapies. Here, we review the current state-of-the-art in nanoparticle-based strategies designed to potentiate cancer immunotherapies, including cancer vaccines with subunit antigens (e.g., oncoproteins, mutated neo-antigens, DNA and mRNA antigens) and whole-cell tumor antigens, dendritic cell-based vaccines, artificial antigen-presenting cells, and immunotherapeutics based on immunogenic cell death, immune checkpoint blockade, and adoptive T-cell therapy.

  12. Nanoparticle Drug Delivery Systems Designed to Improve Cancer Vaccines and Immunotherapy

    Directory of Open Access Journals (Sweden)

    Yuchen Fan

    2015-08-01

    Full Text Available Recent studies have demonstrated great therapeutic potential of educating and unleashing our own immune system for cancer treatment. However, there are still major challenges in cancer immunotherapy, including poor immunogenicity of cancer vaccines, off-target side effects of immunotherapeutics, as well as suboptimal outcomes of adoptive T cell transfer-based therapies. Nanomaterials with defined physico-biochemical properties are versatile drug delivery platforms that may address these key technical challenges facing cancer vaccines and immunotherapy. Nanoparticle systems have been shown to improve targeted delivery of tumor antigens and therapeutics against immune checkpoint molecules, amplify immune activation via the use of new stimuli-responsive or immunostimulatory materials, and augment the efficacy of adoptive cell therapies. Here, we review the current state-of-the-art in nanoparticle-based strategies designed to potentiate cancer immunotherapies, including cancer vaccines with subunit antigens (e.g., oncoproteins, mutated neo-antigens, DNA and mRNA antigens and whole-cell tumor antigens, dendritic cell-based vaccines, artificial antigen-presenting cells, and immunotherapeutics based on immunogenic cell death, immune checkpoint blockade, and adoptive T-cell therapy.

  13. [Factors of Salmonella typhi virulence in relation to the development of new vaccines].

    Science.gov (United States)

    García, J A; Paniagua, J; Pelayo, R; Isibasi, A; Kumate, J

    1992-01-01

    Although many vaccines against typhoid fever have been developed, none have been adapted for their further application on developing countries. In order to get better vaccines, the virulence factors of both S. typhi and S. typhimurium have been studied. Thus, some protection assays have been made using surface antigens involved on virulence or using live attenuated vaccines of bacteria mutated on virulence genes. Here we present a brief review about virulence factors studied so far for the development of new vaccines.

  14. 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.

  15. Dendritic Cell-Based Vaccination in Cancer: Therapeutic Implications Emerging from Murine Models

    Science.gov (United States)

    Mac Keon, Soledad; Ruiz, María Sol; Gazzaniga, Silvina; Wainstok, Rosa

    2015-01-01

    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 toward 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. PMID:26042126

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

    Science.gov (United States)

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

    2016-06-30

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

  17. Cross-sectional and longitudinal analysis of cancer vaccination trials registered on the US Clinical Trials Database demonstrates paucity of immunological trial endpoints and decline in registration since 2008

    Directory of Open Access Journals (Sweden)

    Lu L

    2014-09-01

    include: 1 vaccination against a small range of antigens; 2 naked delivery of antigen; 3 investigation of less immunogenic cancer types; and 4 investigation in the setting of established disease. In addition, the prevalence of late phase failure may be due to inadequate assessment of survival-related endpoints in Phase II trials. The clinical trial development of tumor vaccines should include mechanism-based translational endpoints, as well as the discovery of immune biomarkers with which to stratify, monitor, and prognosticate patients. Keywords: cancer vaccination, cancer prevention, clinical trials, translational trial endpoints, immunotherapy

  18. Intrarectal vaccination with recombinant vaccinia virus expressing carcinoembronic antigen induces mucosal and systemic immunity and prevents progression of colorectal cancer.

    Science.gov (United States)

    Kim-Schulze, Seunghee; Kim, Hong Sung; Wainstein, Alberto; Kim, Dae Won; Yang, Wein Cui; Moroziewicz, Dorota; Mong, Phyllus Y; Bereta, Michal; Taback, Bret; Wang, Qin; Kaufman, Howard L

    2008-12-01

    The gastrointestinal mucosa contains an intact immune system that protects the host from pathogens and communicates with the systemic immune system. Absorptive epithelial cells in the mucosa give rise to malignant tumors although the interaction between tumor cells and the mucosal immune system is not well defined. The pathophysiology of colorectal cancer has been elucidated through studies of hereditary syndromes, such as familial adenomatous polyposis, a cancer predisposition syndrome caused by germline mutations in the adenomatous polyposis coli tumor suppressor gene. Patients with FAP develop adenomas and inevitably progress to invasive carcinomas by the age of 40. To better delineate the role of mucosal immunity in colorectal cancer, we evaluated the efficacy of intrarectal recombinant vaccinia virus expressing the human carcinoembryonic Ag (CEA) in a murine FAP model in which mice are predisposed to colorectal cancer and also express human CEA in the gut. Mucosal vaccination reduced the incidence of spontaneous adenomas and completely prevented progression to invasive carcinoma. The therapeutic effects were associated with induction of mucosal CEA-specific IgA Ab titers and CD8(+) CTLs. Mucosal vaccination was also associated with an increase in systemic CEA-specific IgG Ab titers, CD4(+) and CD8(+) T cell responses and resulted in growth inhibition of s.c. implanted CEA-expressing tumors suggesting communication between mucosal and systemic immune compartments. Thus, intrarectal vaccination induces mucosal and systemic antitumor immunity and prevents progression of spontaneous colorectal cancer. These results have implications for the prevention of colorectal cancer in high-risk individuals.

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

    Directory of Open Access Journals (Sweden)

    Manisha Nair

    2012-01-01

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

  20. Sipuleucel-T: Prototype for development of anti-tumor vaccines.

    Science.gov (United States)

    Carballido, Estrella; Fishman, Mayer

    2011-04-01

    Prostate cancer immunotherapy officially debuted with the recent FDA approval of Sipuleucel-T. The novel trend of cancer immunotherapy relies on the identification of particular tumor-associated antigens, like prostatic acid phosphatase (PAP). Sipuleucel-T consists of autologous dendritic cells activated in vitro with recombinant fusion protein PA2024, PAP-linked to granulocyte-macrophage colony-stimulating factor. Sipuleucel-T represents a prototype for the development of cancer vaccines. Preclinical and clinical data as well as landmark studies for the existing narrow chemotherapy alternatives and early immunotherapy trials will be discussed. The pivotal trial demonstrated a 4.1-month difference of median survival, but with no effect on time to progression in asymptomatic or minimally symptomatic metastatic castrate-resistant patients. Several immunologic effects were observed in the treated population, including antibody and T cell-specific activity to P2024 and PAP. With all new therapies the extent of clinical and objective benefits versus encountered limitations should be evaluated. This review highlights the events and decisions in the process of the development of Sipuleucel-T. We discuss how this successful immunotherapy outcome challenges us to use it as a starting point for variations to or try to amplify practical anticancer progress within the antitumor vaccine paradigm.

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    BACKGROUND: Virus-like particles (VLPs) represent a significant advance in the development of subunit vaccines, combining high safety and efficacy. Their particulate nature and dense repetitive subunit organization makes them ideal scaffolds for display of vaccine antigens. Traditional approaches...

  2. Health Impact of Rotavirus Vaccination in Developing Countries: Progress and Way Forward.

    Science.gov (United States)

    Parashar, Umesh D; Johnson, Hope; Steele, A Duncan; Tate, Jacqueline E

    2016-05-01

    Two rotavirus vaccines have been licensed in >100 countries worldwide since 2006. As of October 2105, these vaccines have been implemented in the national immunization programs of 79 countries, including 36 low-income countries that are eligible for support for vaccine purchase from Gavi, the Vaccine Alliance. Rotavirus vaccines were initially introduced in Australia and countries of the Americas and Europe after completion of successful clinical trials in these regions, and the impact of routine vaccination in reducing the health burden of severe childhood gastroenteritis in these regions has been well documented. Because of concerns around the performance of orally administered rotavirus vaccines in developing countries, vaccine implementation in these settings only began after additional clinical trials were completed and the World Health Organization issued a global recommendation for use of rotavirus vaccines in 2009. This supplementary issue of Clinical Infectious Diseases includes a collection of articles describing the impact and effectiveness of routine rotavirus vaccination in developing countries that were among the early adopters of rotavirus vaccine. The data highlight the benefits of vaccination and should provide valuable evidence to sustain vaccine use in these countries and encourage other countries to adopt routine rotavirus vaccination to reduce the health burden of severe childhood gastroenteritis.

  3. A case study using the United Republic of Tanzania: costing nationwide HPV vaccine delivery using the WHO Cervical Cancer Prevention and Control Costing Tool

    Directory of Open Access Journals (Sweden)

    Hutubessy Raymond

    2012-11-01

    Full Text Available Abstract Background The purpose, methods, data sources and assumptions behind the World Health Organization (WHO Cervical Cancer Prevention and Control Costing (C4P tool that was developed to assist low- and middle-income countries (LMICs with planning and costing their nationwide human papillomavirus (HPV vaccination program are presented. Tanzania is presented as a case study where the WHO C4P tool was used to cost and plan the roll-out of HPV vaccines nationwide as part of the national comprehensive cervical cancer prevention and control strategy. Methods The WHO C4P tool focuses on estimating the incremental costs to the health system of vaccinating adolescent girls through school-, health facility- and/or outreach-based strategies. No costs to the user (school girls, parents or caregivers are included. Both financial (or costs to the Ministry of Health and economic costs are estimated. The cost components for service delivery include training, vaccination (health personnel time and transport, stationery for tally sheets and vaccination cards, and so on, social mobilization/IEC (information, education and communication, supervision, and monitoring and evaluation (M&E. The costs of all the resources used for HPV vaccination are totaled and shown with and without the estimated cost of the vaccine. The total cost is also divided by the number of doses administered and number of fully immunized girls (FIGs to estimate the cost per dose and cost per FIG. Results Over five years (2011 to 2015, the cost of establishing an HPV vaccine program that delivers three doses of vaccine to girls at schools via phased national introduction (three regions in year 1, ten regions in year 2 and all 26 regions in years 3 to 5 in Tanzania is estimated to be US$9.2 million (excluding vaccine costs and US$31.5 million (with vaccine assuming a vaccine price of US$5 (GAVI 2011, formerly the Global Alliance for Vaccines and Immunizations. This is equivalent to a

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

    Science.gov (United States)

    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.

  5. Vaccines against human papillomavirus and perspectives for the prevention and control of cervical cancer Vacunas contra virus del papiloma humano y perspectivas para la prevención y el control del cáncer cervicouterino

    OpenAIRE

    Alejandro García-Carrancá

    2003-01-01

    Today, "persistent" infections by certain types of human papillomavirus (HPV) are considered necessary for developing cervical cancer. Producing efficient vaccines against these viruses may eventually lead to a great reduction in incidence and mortality rates of this cancer. In the case of HPV, the production of traditional vaccines usually based in dead or attenuated viruses is not possible due in part to the lack of systems where large quantities of viral particles could be obtained. Fortun...

  6. Innovative bioinformatic approaches for developing peptide-based vaccines against hypervariable viruses.

    Science.gov (United States)

    Sirskyj, Danylo; Diaz-Mitoma, Francisco; Golshani, Ashkan; Kumar, Ashok; Azizi, Ali

    2011-01-01

    The application of the fields of pharmacogenomics and pharmacogenetics to vaccine design has been recently labeled 'vaccinomics'. This newly named area of vaccine research, heavily intertwined with bioinformatics, seems to be leading the charge in developing novel vaccines for currently unmet medical needs against hypervariable viruses such as human immunodeficiency virus (HIV), hepatitis C and emerging avian and swine influenza. Some of the more recent bioinformatic approaches in the area of vaccine research include the use of epitope determination and prediction algorithms for exploring the use of peptide epitopes as vaccine immunogens. This paper briefly discusses and explores some current uses of bioinformatics in vaccine design toward the pursuit of peptide vaccines for hypervariable viruses. The various informatics and vaccine design strategies attempted by other groups toward hypervariable viruses will also be briefly examined, along with the strategy used by our group in the design and synthesis of peptide immunogens for candidate HIV and influenza vaccines.

  7. Development of a recombinant, chimeric tetravalent dengue vaccine candidate.

    Science.gov (United States)

    Osorio, Jorge E; Partidos, Charalambos D; Wallace, Derek; Stinchcomb, Dan T

    2015-12-10

    Dengue is a significant threat to public health worldwide. Currently, there are no licensed vaccines available for dengue. Takeda Vaccines Inc. is developing a live, attenuated tetravalent dengue vaccine candidate (TDV) that consists of an attenuated DENV-2 strain (TDV-2) and three chimeric viruses containing the prM and E protein genes of DENV-1, -3 and -4 expressed in the context of the attenuated TDV-2 genome backbone (TDV-1, TDV-3, and TDV-4, respectively). TDV has been shown to be immunogenic and efficacious in nonclinical animal models. In interferon-receptor deficient mice, the vaccine induces humoral neutralizing antibody responses and cellular immune responses that are sufficient to protect from lethal challenge with DENV-1, DENV-2 or DENV-4. In non-human primates, administration of TDV induces innate immune responses as well as long lasting antibody and cellular immunity. In Phase 1 clinical trials, the safety and immunogenicity of two different formulations were assessed after intradermal or subcutaneous administration to healthy, flavivirus-naïve adults. TDV administration was generally well-tolerated independent of dose and route. The vaccine induced neutralizing antibody responses to all four DENV serotypes: after a single administration of the higher formulation, 24-67%% of the subjects seroconverted to all four DENV and >80% seroconverted to three or more viruses. In addition, TDV induced CD8(+) T cell responses to the non-structural NS1, NS3 and NS5 proteins of DENV. TDV has been also shown to be generally well tolerated and immunogenic in a Phase 2 clinical trial in dengue endemic countries in adults and children as young as 18 months. Additional clinical studies are ongoing in preparation for a Phase 3 safety and efficacy study.

  8. A review of vaccine development and research for industry animals in Korea

    OpenAIRE

    Lee, Nak-Hyung; Lee, Jung-Ah; Park, Seung-Yong; Song, Chang-Seon; Choi, In-Soo; Lee, Joong-Bok

    2012-01-01

    Vaccination has proven to be the most cost-effective strategy for controlling a wide variety of infectious diseases in humans and animals. For the last decade, veterinary vaccines have been substantially developed and demonstrated their effectiveness against many diseases. Nevertheless, new vaccines are greatly demanded to effectively control newly- and re-emerging pathogens in livestock. However, development of veterinary vaccines is a challenging task, in part, due to a variety of pathogens...

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

    Directory of Open Access Journals (Sweden)

    Gavin C. Bowick

    2010-01-01

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

  10. [Cancer of cervix in Chile. Too much vaccine amid a neglected Papanicolau].

    Science.gov (United States)

    Fica, Alberto

    2014-04-01

    The Chilean Ministry of Health announced the incorporation of a human papillomavirus (HPV) vaccine to prevent cervix uterine cancer (CUC) into the national immunization program during year 2014 This decision was adopted despite of two opposing documents and a significant decrease in cervical cancer associated mortality due to cytological cervical screening. The burden of disease attributed to CUC has declined in Chile and current cost-effectiveness studies should be reviewed considering this decreasing trend, the progressive decrease in coverage rates observed during the past years, the potential need for aditional doses and lower vaccine costs if vaccine is acquired through the PAHO revolving fund. Moreover, serious adverse events associated with these vaccines, which in some countries are more frequent than CUC associated mortality, have not been thoroughly evaluated and are probably underreported. The decision to incorporate the vaccine occurs in a context of progressive weakening of the national cervical screening program leading to a reduced population coverage. This situation jepeordizes the achievements already obtained and poses a challenge to vaccine introduction considering that not all the high-risk viral subtypes are included and thus the risk for CUC does not disappear making cervical screening a vital component of the program that needs to be maintained. This governmental resolution requires a more solid scientific foundation and should not be implemented without resolving current cervical screening shortcomings.

  11. 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

  12. 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.

  13. Self-replicating alphavirus RNA vaccines.

    Science.gov (United States)

    Ljungberg, Karl; Liljeström, Peter

    2015-02-01

    Recombinant nucleic acids are considered as promising next-generation vaccines. These vaccines express the native antigen upon delivery into tissue, thus mimicking live attenuated vaccines without having the risk of reversion to pathogenicity. They also stimulate the innate immune system, thus potentiating responses. Nucleic acid vaccines are easy to produce at reasonable cost and are stable. During the past years, focus has been on the use of plasmid DNA for vaccination. Now mRNA and replicon vaccines have come into focus as promising technology platforms for vaccine development. This review discusses self-replicating RNA vaccines developed from alphavirus expression vectors. These replicon vaccines can be delivered as RNA, DNA or as recombinant virus particles. All three platforms have been pre-clinically evaluated as vaccines against a number of infectious diseases and cancer. Results have been very encouraging and propelled the first human clinical trials, the results of which have been promising.

  14. Development of TV003/TV005, a single dose, highly immunogenic live attenuated dengue vaccine; what makes this vaccine different from the Sanofi-Pasteur CYD™ vaccine?

    Science.gov (United States)

    Whitehead, Stephen S

    2016-01-01

    Dengue is caused by four serotype-distinct dengue viruses (DENVs), and developing a multivalent vaccine against dengue has not been straightforward since partial immunity to DENV may predispose to more severe disease upon subsequent DENV infection. The vaccine that is furthest along in development is CYD™, a live attenuated tetravalent vaccine (LATV) produced by Sanofi Pasteur. Although the multi-dose vaccine demonstrated protection against severe dengue, its overall efficacy was limited by DENV serotype, serostatus at vaccination, region and age. The National Institute of Allergy and Infectious Diseases has developed the LATV dengue vaccines TV003/TV005. A single dose of either TV003 or TV005 induced seroconversion to four DENV serotypes in 74-92% (TV003) and 90% (TV005) of flavivirus seronegative adults and elicited near-sterilizing immunity to a second dose of vaccine administered 6-12 months later. The important differences in the structure, infectivity and immune responses to TV003/TV005 are compared with CYD™.

  15. Humoral Immune Response to Keyhole Limpet Haemocyanin, the Protein Carrier in Cancer Vaccines

    Directory of Open Access Journals (Sweden)

    A. Kantele

    2011-01-01

    Full Text Available Keyhole limpet haemocyanin (KLH appears to be a promising protein carrier for tumor antigens in numerous cancer vaccine candidates. The humoral immune response to KLH was characterized at the single-cell level with ELISPOT combined with separations of cell populations according to their expression of homing receptors (HRs. The analysis of HR expressions is expected to reveal the targeting of the immune response in the body. Eight orally primed and four nonprimed volunteers received KLH-vaccine subcutaneously. Circulating KLH-specific plasmablasts were found in all volunteers, 60 KLH-specific plasmablasts/106 PBMC in the nonprimed and 136/106 in the primed group. The proportion of L-selectin+ plasmablasts proved high and integrin α4β7+ low. KLH serving as protein carrier in several vaccines, the homing profile of KLH-specific response may be applicable to the cancer antigen parts in the same vaccines. The present data reflect a systemic homing profile, which appears advantageous for the targeting of immune response to cancer vaccines.

  16. Exploring the cost-effectiveness of HPV vaccination in Vietnam: insights for evidence-based cervical cancer prevention policy.

    Science.gov (United States)

    Kim, Jane J; Kobus, Katie E; Diaz, Mireia; O'Shea, Meredith; Van Minh, Hoang; Goldie, Sue J

    2008-07-29

    Using mathematical models of cervical cancer for the northern and southern regions of Vietnam, we assessed the cost-effectiveness of cervical cancer prevention strategies and the tradeoffs between a national and region-based policy in Vietnam. With 70% vaccination and screening coverage, lifetime risk of cancer was reduced by 20.4-76.1% with vaccination of pre-adolescent girls and/or screening of older women. Only when the cost per vaccinated girl was low (i.e., I$100), screening alone was most cost-effective. When optimal policies differed between regions, implementing a national strategy resulted in health and economic inefficiencies. HPV vaccination appears to be an attractive cervical cancer prevention strategy for Vietnam, provided high coverage can be achieved in young pre-adolescent girls, cost per vaccinated girl is

  17. Nontyphoidal salmonella disease: Current status of vaccine research and development.

    Science.gov (United States)

    Tennant, Sharon M; MacLennan, Calman A; Simon, Raphael; Martin, Laura B; Khan, M Imran

    2016-06-01

    Among more than 2500 nontyphoidal Salmonella enterica (NTS) serovars, S. enterica serovar Typhimurium and S. enterica serovar Enteritidis account for approximately fifty percent of all human isolates of NTS reported globally. The global incidence of NTS gastroenteritis in 2010 was estimated to be 93 million cases, approximately 80 million of which were contracted via food-borne transmission. It is estimated that 155,000 deaths resulted from NTS in 2010. NTS also causes severe, extra-intestinal, invasive bacteremia, referred to as invasive nontyphoidal Salmonella (iNTS) disease. iNTS disease usually presents as a febrile illness, frequently without gastrointestinal symptoms, in both adults and children. Symptoms of iNTS are similar to malaria, often including fever (>90%) and splenomegaly (>40%). The underlying reasons for the high rates of iNTS disease in Africa are still being elucidated. Evidence from animal and human studies supports the feasibility of developing a safe and effective vaccine against iNTS. Both antibodies and complement can kill Salmonella species in vitro. Proof-of-principle studies in animal models have demonstrated efficacy for live attenuated and subunit vaccines that target the O-antigens, flagellin proteins, and other outer membrane proteins of serovars Typhimurium and Enteritidis. More recently, a novel delivery strategy for NTS vaccines has been developed: the Generalized Modules for Membrane Antigens (GMMA) technology which presents surface polysaccharides and outer membrane proteins in their native conformation. GMMA technology is self-adjuvanting, as it delivers multiple pathogen-associated molecular pattern molecules. GMMA may be particularly relevant for low- and middle-income countries as it has the potential for high immunologic potency at a low cost and involves a relatively simple production process without the need for complex conjugation. Several vaccines for the predominant NTS serovars Typhimurium and Enteritidis, are

  18. 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

    Directory of Open Access Journals (Sweden)

    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

  19. [Travelers' vaccines].

    Science.gov (United States)

    Ouchi, Kazunobu

    2011-09-01

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

  20. 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.

  1. Enhancing the Breadth and Efficacy of Therapeutic Vaccines for Breast Cancer

    Science.gov (United States)

    2015-10-01

    single antigen such as HER2 in breast cancer is likely to be insufficient - instead we need a repertoire of multiple immunologically validated T cell...Award Number: W81XWH-11-1-0548 TITLE: Enhancing the Breadth and Efficacy of Therapeutic Vaccines for Breast Cancer PRINCIPAL INVESTIGATOR...for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection

  2. Universal Breast Cancer Antigens as Targets Linking Early Detection and Therapeutic Vaccination

    Science.gov (United States)

    2008-09-01

    CYP1B1 ), each overexpressed in >90% of invasive breast cancers but rarely found in normal tissue -- may fill this gap. Such targets, if found at...hTERT and CYP1B1 provide an opportunity for both early detection and cancer vaccination. Objective/Hypothesis: We hypothesize that immunologic responses...in ductal lavage fluid from BRCA1 and BRCA2 mutation carriers The last year has been spent studying genetic polymorphisms in BRCA1 and BRCA2

  3. The introduction of new vaccines into developing countries. V: Will we lose a decade or more in the introduction of dengue vaccines to developing countries?

    Science.gov (United States)

    Mahoney, Richard

    2014-02-12

    Dengue results in as many as 390 million infections annually and causes significant morbidity. A number of efforts are underway to develop vaccines against dengue. The public sector is undertaking efforts to create an enabling environment for vaccine introduction. Recent work by Brooks et al. provides a framework for analyzing which efforts should be undertaken before licensure. They conclude that actions before licensure are required to eliminate the decade or more it normally takes to introduce new vaccines into developing countries. We apply their methodology to dengue and identify a number of critical areas where public sector actions before licensure can greatly accelerate vaccine uptake.

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

    NARCIS (Netherlands)

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

    2005-01-01

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

  5. Overview of developments in the last 10-15 years in recombinant vaccines

    Science.gov (United States)

    This introductory talk will describe the various types of recombinant DNA vaccines that have been developed for the poultry industry. The talk will not discuss the efficacy of specific recombinant DNA vaccines. Instead, I will focus on describing how various recombinant vaccines are made and some ad...

  6. University Students' Knowledge and Attitudes Regarding Cervical Cancer, Human Papillomavirus, and Human Papillomavirus Vaccines in Turkey

    Science.gov (United States)

    Koç, Zeliha

    2015-01-01

    Objectives: The current descriptive study aimed to determine university students' knowledge and attitudes regarding cervical cancer, human papillomavirus (HPV), and HPV vaccines in Turkey. Participants: A total of 800 students participated. Methods: This study was carried out between September 1, 2012, and October 30, 2012, in 8 female…

  7. 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 t

  8. Development of vaccines against Ornithodoros soft ticks: An update.

    Science.gov (United States)

    Díaz-Martín, Verónica; Manzano-Román, Raúl; Obolo-Mvoulouga, Prosper; Oleaga, Ana; Pérez-Sánchez, Ricardo

    2015-04-01

    Ticks are parasites of great medical and veterinary importance since they are vectors of numerous pathogens that affect humans, livestock and pets. Among the argasids, several species of the genus Ornithodoros transmit serious diseases such as tick-borne human relapsing fever (TBRF) and African Swine Fever (ASF). In particular, Ornithodoros erraticus is the main vector of these two diseases in the Mediterranean while O. moubata is the main vector in Africa. The presence of these Ornithodoros ticks in domestic and peridomestic environments may greatly hinder the eradication of TBRF and ASF from endemic areas. In addition, there is a constant threat of reintroduction and spreading of ASF into countries from where it has been eradicated (Spain and Portugal) or where it was never present (the Caucasus, Russia and Eastern Europe). In these countries, the presence of Ornithodoros vectors could have a tremendous impact on ASF transmission and long-term maintenance. Therefore, elimination of these ticks from at least synanthropic environments would contribute heavily to the prevention and control of the diseases they transmit. Tick control is a difficult task and although several methods for such control have been used, none of them has been fully effective against all ticks and the problems they cause. Nevertheless, immunological control using anti-tick vaccines offers an attractive alternative to the traditional use of acaricides. The aim of the present paper is to offer a brief overview of the current status in control measure development for Ornithodoros soft ticks, paying special attention to the development of vaccines against O. erraticus and O. moubata. Thus, our contribution includes an analysis of the chief attributes that the ideal antigens for an anti-tick vaccine should have, an exhaustive compilation and analysis of the scant anti-soft tick vaccine trials carried out to date using both concealed and salivary antigens and, finally, a brief description of the

  9. Challenges in Mucosal HIV Vaccine Development: Lessons from Non-Human Primate Models

    OpenAIRE

    Iskra Tuero; Marjorie Robert-Guroff

    2014-01-01

    An efficacious HIV vaccine is urgently needed to curb the AIDS pandemic. The modest protection elicited in the phase III clinical vaccine trial in Thailand provided hope that this goal might be achieved. However, new approaches are necessary for further advances. As HIV is transmitted primarily across mucosal surfaces, development of immunity at these sites is critical, but few clinical vaccine trials have targeted these sites or assessed vaccine-elicited mucosal immune responses. Pre-clinic...

  10. Development and Evidence for Efficacy of CMV Glycoprotein B Vaccine with MF59 Adjuvant

    OpenAIRE

    Pass, Robert F.

    2009-01-01

    A vaccine comprised of recombinant cytomegalovirus (CMV) envelope glycoprotein B (gB) with MF59 adjuvant developed in the 1990s recently was recently found to have efficacy for prevention of CMV infection in a phase 2 clinical trial in young mothers. This review briefly considers the rationale for gB as a vaccine antigen, the history of this CMV gB vaccine and the data supporting vaccine efficacy.

  11. Cervical Cancer Screening in Partly HPV Vaccinated Cohorts - A Cost-Effectiveness Analysis.

    Directory of Open Access Journals (Sweden)

    Steffie K Naber

    Full Text Available 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 time. At a certain herd immunity level, tailoring screening to vaccination status may no longer be worth the additional effort. Moreover, uniform screening may be the only viable option. We therefore investigated at what level of herd immunity it is cost-effective to also reduce screening intensity in unvaccinated women.We used the MISCAN-Cervix model to determine the optimal screening strategy for a pre-vaccination population and for vaccinated women (~80% decreased risk, assuming a willingness-to-pay of €50,000 per quality-adjusted life year gained. We considered HPV testing, cytology testing and co-testing and varied the start age of screening, the screening interval and the number of lifetime screens. We then calculated the incremental cost-effectiveness ratio (ICER of screening unvaccinated women with the strategy optimized to the pre-vaccination population as compared to with the strategy optimized to vaccinated women, assuming different herd immunity levels.Primary HPV screening with cytology triage was the optimal strategy, with 8 lifetime screens for the pre-vaccination population and 3 for vaccinated women. The ICER of screening unvaccinated women 8 times instead of 3 was €28,085 in the absence of herd immunity. At around 50% herd immunity, the ICER reached €50,000.From a herd immunity level of 50% onwards, screening intensity based on the pre-vaccination risk level becomes cost-ineffective for unvaccinated women. Reducing the screening intensity of uniform screening may then be considered.

  12. Designing HER2 vaccines.

    Science.gov (United States)

    Foy, Teresa M; Fanger, Gary R; Hand, Susan; Gerard, Catherine; Bruck, Claudine; Cheever, Martin A

    2002-06-01

    HER2/neu is a compelling cancer vaccine candidate because it is overexpressed on some cancer cells relative to normal tissues, it is known to be immunogenic in both animal models and in humans, and it is already known to be targetable by the antibody component of the immune system in the form of monoclonal antibody therapy with trastuzumab. Vaccines offer the theoretical advantage of being able to elicit T-cell responses in addition to antibody responses. HER2 vaccines have been shown to provide benefit in animal models and to be immunogenic in humans. However, the optimal vaccine formulation is not yet known and the therapeutic efficacy of the vaccines in humans has not yet been evaluated. HER2 vaccine approaches currently being tested include peptide-based, DNA plasmid-based, and protein-based vaccines. Our group has developed and started testing a protein-based vaccine composed of both the extracellular domain of HER2 and the carboxyl terminal autophosphorylation portion of the intracellular domain. The extracellular domain was retained to provide for antibody targeting. The kinase domain of the intracellular domain was excluded because of its high degree of homology to other human kinases. The carboxyl terminal autophosphorylation domain was retained because it is the most unique and possibly most immunogenic portion of the HER2 molecule with the least homology to other members of the HER family. The vaccine, termed dHER2, is immunogenic in mice and primates. In animal models it can elicit CD8 and CD4 T-cell responses as well as antibody responses that suppress the growth of HER2-positive cancer cells in vitro and in vivo. Vaccine trials are contemplated in patients with breast cancer that will determine whether the vaccine construct is similarly immunogenic in humans.

  13. Development of a new vaccine for the prevention of Lassa fever.

    Directory of Open Access Journals (Sweden)

    2005-06-01

    Full Text Available BACKGROUND: Recent importation of Lassa fever into Germany, the Netherlands, the United Kingdom, and the United States by travelers on commercial airlines from Africa underscores the public health challenge of emerging viruses. Currently, there are no licensed vaccines for Lassa fever, and no experimental vaccine has completely protected nonhuman primates against a lethal challenge. METHODS AND FINDINGS: We developed a replication-competent vaccine against Lassa virus based on attenuated recombinant vesicular stomatitis virus vectors expressing the Lassa viral glycoprotein. A single intramuscular vaccination of the Lassa vaccine elicited a protective immune response in nonhuman primates against a lethal Lassa virus challenge. Vaccine shedding was not detected in the monkeys, and none of the animals developed fever or other symptoms of illness associated with vaccination. The Lassa vaccine induced strong humoral and cellular immune responses in the four vaccinated and challenged monkeys. Despite a transient Lassa viremia in vaccinated animals 7 d after challenge, the vaccinated animals showed no evidence of clinical disease. In contrast, the two control animals developed severe symptoms including rashes, facial edema, and elevated liver enzymes, and ultimately succumbed to the Lassa infection. CONCLUSION: Our data suggest that the Lassa vaccine candidate based on recombinant vesicular stomatitis virus is safe and highly efficacious in a relevant animal model that faithfully reproduces human disease.

  14. Sipuleucel-T: APC 8015, APC-8015, prostate cancer vaccine--Dendreon.

    Science.gov (United States)

    2006-01-01

    Sipuleucel-T [APC 8015, Provenge] is an autologous, dendritic cell-based vaccine under development with Dendreon Corporation for the treatment of androgen-independent and androgen-dependent prostate cancer. It was generated using the company's active immunotherapy platform to stimulate a patient's own immune system to specifically target and destroy cancer cells, while leaving healthy cells unharmed. This approach could provide patients with a meaningful survival benefit and an improved tolerability profile over existing anticancer therapies. Sipuleucel-T selectively targets the prostate-specific antigen (PSA) known as prostatic acid phosphatase (PAP) that is expressed in approximately 95% of prostate cancers. It is produced by ex vivo exposure of dendritic cell precursors to PA 2024, a recombinant fusion protein composed of the PAP target fused to granulocyte-macrophage colony-stimulating factor (GM-CSF) and incorporated into Dendreon's proprietary Antigen Delivery Cassette. Patients are typically administered three intravenous (IV)-infusions of the vaccine over a 1-month period as a complete course of therapy. It is undergoing late-stage clinical evaluation among patients with early and advanced prostate cancer. In November 2003, Kirin Brewery returned to Dendreon the full rights to Sipuleucel-T for Asia. In exchange, Dendreon licensed patent rights relating to the use of certain HLA-DR antibodies to Kirin for $US20 million. This amended agreement enables Dendreon to complete ongoing discussions for a worldwide marketing and sales partnership for Sipuleucel-T. Similarly, Kirin is able to develop its HLA-DR monoclonal antibodies free of potential infringement claims arising from Dendreon's patent rights to HLA-DR. The licensing agreement relates to patent rights owned by Dendreon relating to monoclonal antibodies against the HLA-DR antigen. In addition, Dendreon retains rights to develop and commercialise its two existing HLA-DR monoclonal antibodies, DN 1921 and

  15. The National Cancer Institute's PREVENT Cancer Preclinical Drug Development Program: overview, current projects, animal models, agent development strategies, and molecular targets.

    Science.gov (United States)

    Shoemaker, Robert H; Suen, Chen S; Holmes, Cathy A; Fay, Judith R; Steele, Vernon E

    2016-02-01

    The PREVENT Cancer Preclinical Drug Development Program (PREVENT) is a National Cancer Institute, Division of Cancer Prevention (NCI, DCP)-supported program whose primary goal is to bring new cancer preventive interventions (small molecules and vaccines) and biomarkers through preclinical development towards clinical trials by creating partnerships between the public sector (eg, academia, industry) and DCP. PREVENT has a formalized structure for moving interventions forward in the prevention pipeline using a stage-gate process with go/no go decision points along the critical path for development. This review describes the structure of the program, its focus areas, and provides examples of projects currently in the pipeline.

  16. 78 FR 50425 - Prospective Grant of Exclusive License: Development of Brachyury Tumor Associated Antigens as...

    Science.gov (United States)

    2013-08-19

    ... to the development of cancer vaccines utilizing pox virus vectors encoding proteins involved in... HUMAN SERVICES National Institutes of Health Prospective Grant of Exclusive License: Development of Brachyury Tumor Associated Antigens as Cancer Vaccines for Colorectal Cancer AGENCY: National Institutes...

  17. Dendritic cell based tumor vaccination in prostate and renal cell cancer: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Andreas Draube

    Full Text Available BACKGROUND: More than 200 clinical trials have been performed using dendritic cells (DC as cellular adjuvants in cancer. Yet the key question whether there is a link between immune and clinical response remains unanswered. Prostate and renal cell cancer (RCC have been extensively studied for DC-based immunotherapeutic interventions and were therefore chosen to address the above question by means of a systematic review and meta-analysis. METHODOLOGY/PRINCIPAL FINDINGS: Data was obtained after a systematic literature search from clinical trials that enrolled at least 6 patients. Individual patient data meta-analysis was performed by means of conditional logistic regression grouped by study. Twenty nine trials involving a total of 906 patients were identified in prostate cancer (17 and RCC (12. Objective response rates were 7.7% in prostate cancer and 12.7% in RCC. The combined percentages of objective responses and stable diseases (SD amounted to a clinical benefit rate (CBR of 54% in prostate cancer and 48% in RCC. Meta-analysis of individual patient data (n = 403 revealed the cellular immune response to have a significant influence on CBR, both in prostate cancer (OR 10.6, 95% CI 2.5-44.1 and in RCC (OR 8.4, 95% CI 1.3-53.0. Furthermore, DC dose was found to have a significant influence on CBR in both entities. Finally, for the larger cohort of prostate cancer patients, an influence of DC maturity and DC subtype (density enriched versus monocyte derived DC as well as access to draining lymph nodes on clinical outcome could be demonstrated. CONCLUSIONS/SIGNIFICANCE: As a 'proof of principle' a statistically significant effect of DC-mediated cellular immune response and of DC dose on CBR could be demonstrated. Further findings concerning vaccine composition, quality control, and the effect of DC maturation status are relevant for the immunological development of DC-based vaccines.

  18. Challenges in early clinical development of adjuvanted vaccines.

    Science.gov (United States)

    Della Cioppa, Giovanni; Jonsdottir, Ingileif; Lewis, David

    2015-06-08

    A three-step approach to the early development of adjuvanted vaccine candidates is proposed, the goal of which is to allow ample space for exploratory and hypothesis-generating human experiments and to select dose(s) and dosing schedule(s) to bring into full development. Although the proposed approach is more extensive than the traditional early development program, the authors suggest that by addressing key questions upfront the overall time, size and cost of development will be reduced and the probability of public health advancement enhanced. The immunogenicity end-points chosen for early development should be critically selected: an established immunological parameter with a well characterized assay should be selected as primary end-point for dose and schedule finding; exploratory information-rich end-points should be limited in number and based on pre-defined hypothesis generating plans, including system biology and pathway analyses. Building a pharmacodynamic profile is an important aspect of early development: to this end, multiple early (within 24h) and late (up to one year) sampling is necessary, which can be accomplished by sampling subgroups of subjects at different time points. In most cases the final target population, even if vulnerable, should be considered for inclusion in early development. In order to obtain the multiple formulations necessary for the dose and schedule finding, "bed-side mixing" of various components of the vaccine is often necessary: this is a complex and underestimated area that deserves serious research and logistical support.

  19. Are Older Adults Up-to-Date With Cancer Screening and Vaccinations?

    Directory of Open Access Journals (Sweden)

    Douglas Shenson, MD, MPH, MS

    2005-07-01

    Full Text Available Introduction Public health organizations in the United States emphasize the importance of providing routine screening for breast cancer, cervical cancer, and colorectal cancer, as well as vaccinations against influenza and pneumococcal disease among older adults. We report a composite measure of adults aged 50 years and older who receive recommended cancer screening services and vaccinations. Methods We analyzed state data from the 2002 Behavioral Risk Factor Surveillance System, which included 105,860 respondents aged 50 and older. We created a composite measure that included colonoscopy or sigmoidoscopy within 10 years or a fecal occult blood test in the past year, an influenza vaccination in the past year, a Papanicolaou test within 3 years for women with an intact cervix, a mammogram, and for adults aged 65 and older, a pneumonia vaccination during their lifetime. We performed separate analyses for four age and sex groups: men aged 50 to 64, women aged 50 to 64, men aged 65 and older, and women aged 65 and older. Results The percentage of each age and sex group that was up-to-date according to our composite measure ranged from 21.1% of women aged 50 to 64 (four tests to 39.6% of men aged 65 and older (three tests. For each group, results varied by income, education, race/ethnicity, insurance status, and whether the respondent had a personal physician. Conclusion These results suggest the need to improve the delivery of cancer screenings and vaccinations among adults aged 50 and older. We propose continued efforts to measure use of clinical preventive services.

  20. Development of a Cost-Effective Educational Tool to Promote Acceptance of the HPV Vaccination by Hispanic Mothers.

    Science.gov (United States)

    Brueggmann, Doerthe; Opper, Neisha; Felix, Juan; Groneberg, David A; Mishell, Daniel R; Jaque, Jenny M

    2016-06-01

    Although vaccination against the Human Papilloma Virus (HPV) reduces the risk of related morbidities, the vaccine uptake remains low in adolescents. This has been attributed to limited parental knowledge and misconceptions. In this cross sectional study, we assessed the (1) clarity of educational material informing Hispanic mothers about HPV, cervical cancer and the HPV vaccine, (2) determined vaccination acceptability and (3) identified predictors of vaccine acceptance in an underserved health setting. 418 Hispanic mothers received the educational material and completed an anonymous survey. 91 % of participants understood most or all of the information provided. 77 % of participants reported vaccine acceptance for their children; this increased to 84 % when only those with children eligible to receive vaccination were included. Significant positive predictors of maternal acceptance of the HPV vaccine for their children were understanding most or all of the provided information, older age and acceptance of the HPV vaccine for themselves. Concerns about safety and general dislike of vaccines were negatively associated with HPV vaccine acceptance. Prior knowledge, level of education, previous relevant gynecologic history, general willingness to vaccinate and other general beliefs about vaccines were not significantly associated with HPV vaccine acceptance. The majority of participants reported understanding of the provided educational material. Vaccine acceptability was fairly high, but was even higher among those who understood the information. This study documents a cost-effective way to provide Hispanic mothers with easy-to-understand HPV-related information that could increase parental vaccine acceptability and future vaccine uptake among their children.

  1. Analysis of cell-mediated immune responses in support of dengue vaccine development efforts.

    Science.gov (United States)

    Rothman, Alan L; Currier, Jeffrey R; Friberg, Heather L; Mathew, Anuja

    2015-12-10

    Dengue vaccine development has made significant strides, but a better understanding of how vaccine-induced immune responses correlate with vaccine efficacy can greatly accelerate development, testing, and deployment as well as ameliorate potential risks and safety concerns. Advances in basic immunology knowledge and techniques have already improved our understanding of cell-mediated immunity of natural dengue virus infection and vaccination. We conclude that the evidence base is adequate to argue for inclusion of assessments of cell-mediated immunity as part of clinical trials of dengue vaccines, although further research to identify useful correlates of protective immunity is needed.

  2. Vaccine production training to develop the workforce of foreign institutions supported by the BARDA influenza vaccine capacity building program.

    Science.gov (United States)

    Tarbet, E Bart; Dorward, James T; Day, Craig W; Rashid, Kamal A

    2013-03-15

    In the event of an influenza pandemic, vaccination will be the best method to limit virus spread. However, lack of vaccine biomanufacturing capacity means there will not be enough vaccine for the world's population. The U.S. Department of Health and Human Services, Biomedical Advanced Research and Development Authority (BARDA) provides support to the World Health Organization to enhance global vaccine production capacity in developing countries. However, developing a trained workforce in some of those countries is necessary. Biomanufacturing is labor-intensive, requiring unique skills not found in traditional academic programs. Employees must understand the scientific basis of biotechnology, operate specialized equipment, and work in an environment regulated by good manufacturing practices (cGMP). Therefore, BARDA supported development of vaccine biomanufacturing training at Utah State University. The training consisted of a three-week industry-focused course for participants from institutions supported by the BARDA and WHO influenza vaccine production capacity building program. The curriculum was divided into six components: (1) biosafety, (2) cell culture and growth of cells in bioreactors, (3) virus assays and inactivation, (4) scale-up strategies, (5) downstream processing, and (6) egg- and cell-based vaccine production and cGMP. Lectures were combined with laboratory exercises to provide a balance of theory and hands-on training. The initial course included sixteen participants from seven countries including: Egypt, Romania, Russia, Serbia, South Korea, Thailand, and Vietnam. The participant's job responsibilities included: Production, Quality Control, Quality Assurance, and Research; and their education ranged from bachelors to doctoral level. Internal course evaluations utilized descriptive methods including surveys, observation of laboratory activities, and interviews with participants. Generally, participants had appropriate academic backgrounds, but

  3. Vulval cancer and HPV vaccination in recurrent disease

    DEFF Research Database (Denmark)

    Gustafson, L W; Gade, Melina; Blaakær, Jan

    2014-01-01

    KEY CLINICAL MESSAGE: A woman diagnosed with a recurrent vulval carcinoma after initial treatment with radiochemotherapy is presented. After three additional relapses she was vaccinated with Gardasil. She has had no relapses in her vulvar area for 39 months and an overall progression-free survival...

  4. 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

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

    Science.gov (United States)

    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.

  6. Immunotherapy and therapeutic vaccines in prostate cancer:an update on current strategies and clinical implications

    Institute of Scientific and Technical Information of China (English)

    B Harpreet Singh; James L Gulley

    2014-01-01

    In recent years, immunotherapy has emerged as a viable and attractive strategy for the treatment of prostate cancer. While there are multiple ways to target the immune system, therapeutic cancer vaccines and immune checkpoint inhibitors have been most successful in late-stage clinical trials. The landmark Food and Drug Administration approval of sipuleucel-T for asymptomatic or minimally symptomatic metastatic prostate cancer set the stage for ongoing phase III trials with the cancer vaccine PSA-TRICOM and the immune checkpoint inhibitor ipilimumab. A common feature of these immune-based therapies is the appearance of improved overall survival without short-term changes in disease progression. This class effect appears to be due to modulation of tumor growth rate kinetics, in which the activated immune system exerts constant immunologic pressure that slows net tumor growth. Emerging data suggest that the ideal population for clinical trials of cancer vaccines is patients with lower tumor volume and less aggressive disease. Combination strategies that combine immunotherapy with standard therapies have been shown to augment both immune response and clinical beneift.

  7. Immunotherapy and therapeutic vaccines in prostate cancer: an update on current strategies and clinical implications

    Directory of Open Access Journals (Sweden)

    B Harpreet Singh

    2014-06-01

    Full Text Available In recent years, immunotherapy has emerged as a viable and attractive strategy for the treatment of prostate cancer. While there are multiple ways to target the immune system, therapeutic cancer vaccines and immune checkpoint inhibitors have been most successful in late-stage clinical trials. The landmark Food and Drug Administration approval of sipuleucel-T for asymptomatic or minimally symptomatic metastatic prostate cancer set the stage for ongoing phase III trials with the cancer vaccine PSA-TRICOM and the immune checkpoint inhibitor ipilimumab. A common feature of these immune-based therapies is the appearance of improved overall survival without short-term changes in disease progression. This class effect appears to be due to modulation of tumor growth rate kinetics, in which the activated immune system exerts constant immunologic pressure that slows net tumor growth. Emerging data suggest that the ideal population for clinical trials of cancer vaccines is patients with lower tumor volume and less aggressive disease. Combination strategies that combine immunotherapy with standard therapies have been shown to augment both immune response and clinical benefit.

  8. Helicobacter pylori CagA: from pathogenic mechanisms to its use as an anti-cancer vaccine

    Directory of Open Access Journals (Sweden)

    Markus eStein

    2013-10-01

    Full Text Available Helicobacter pylori colonizes the gastric mucosa of more than 50% of the human population, causing chronic inflammation, which however is largely asymptomatic. Nevertheless, H. pylori-infected subjects can develop chronic gastritis, peptic ulcer, gastric mucosa-associated lymphoid tissue (MALT lymphoma, and gastric cancer. Chronic exposure to the pathogen and its ability to induce epithelial-to-mesenchymal transition (EMT through the injection of CagA into gastric epithelial cells may be key triggers of carcinogenesis. By deregulating cell-cell and cell-matrix interactions as well as DNA methylation, histone modifications, expression of micro RNAs, and resistance to apoptosis, EMT can actively contribute to early stages of the cancer formation. Host response to the infection significantly contributes to disease development and the concomitance of particular genotypes of both pathogen and host may turn into the most severe outcomes. T regulatory cells (Treg have been recently demonstrated to play an important role in H. pylori-related disease development and at the same time the Treg-induced tolerance has been proposed as a possible mechanism that leads to less severe disease. Efficacy of antibiotic therapies of H. pylori infection has significantly dropped. Unfortunately, no vaccine against H. pylori is currently licensed, and protective immunity mechanisms against H. pylori are only partially understood. In spite of promising results obtained in animal models of infection with a number of vaccine candidates, few clinical trials have been conducted so far and with no satisfactory outcomes. However, prophylactic vaccination may be the only means to efficiently prevent H. pylori-associated cancers.

  9. Epigenetic potentiation of NY-ESO-1 vaccine therapy in human ovarian cancer.

    Science.gov (United States)

    Odunsi, Kunle; Matsuzaki, Junko; James, Smitha R; Mhawech-Fauceglia, Paulette; Tsuji, Takemasa; Miller, Austin; Zhang, Wa; Akers, Stacey N; Griffiths, Elizabeth A; Miliotto, Anthony; Beck, Amy; Batt, Carl A; Ritter, Gerd; Lele, Shashikant; Gnjatic, Sacha; Karpf, Adam R

    2014-01-01

    The cancer-testis/cancer-germline antigen NY-ESO-1 is a vaccine target in epithelial ovarian cancer (EOC), but its limited expression is a barrier to vaccine efficacy. As NY-ESO-1 is regulated by DNA methylation, we hypothesized that DNA methyltransferase (DNMT) inhibitors may augment NY-ESO-1 vaccine therapy. In agreement, global DNA hypomethylation in EOC was associated with the presence of circulating antibodies to NY-ESO-1. Pre-clinical studies using EOC cell lines showed that decitabine treatment enhanced both NY-ESO-1 expression and NY-ESO-1-specific CTL-mediated responses. Based on these observations, we performed a phase I dose-escalation trial of decitabine, as an addition to NY-ESO-1 vaccine and doxorubicin liposome (doxorubicin) chemotherapy, in 12 patients with relapsed EOC. The regimen was safe, with limited and clinically manageable toxicities. Both global and promoter-specific DNA hypomethylation occurred in blood and circulating DNAs, the latter of which may reflect tumor cell responses. Increased NY-ESO-1 serum antibodies and T cell responses were observed in the majority of patients, and antibody spreading to additional tumor antigens was also observed. Finally, disease stabilization or partial clinical response occurred in 6/10 evaluable patients. Based on these encouraging results, evaluation of similar combinatorial chemo-immunotherapy regimens in EOC and other tumor types is warranted.

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

    Directory of Open Access Journals (Sweden)

    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.

  11. Extracellular Vesicles: Role in Inflammatory Responses and Potential Uses in Vaccination in Cancer and Infectious Diseases

    Directory of Open Access Journals (Sweden)

    João Henrique Campos

    2015-01-01

    Full Text Available Almost all cells and organisms release membrane structures containing proteins, lipids, and nucleic acids called extracellular vesicles (EVs, which have a wide range of functions concerning intercellular communication and signaling events. Recently, the characterization and understanding of their biological role have become a main research area due to their potential role in vaccination, as biomarkers antigens, early diagnostic tools, and therapeutic applications. Here, we will overview the recent advances and studies of Evs shed by tumor cells, bacteria, parasites, and fungi, focusing on their inflammatory role and their potential use in vaccination and diagnostic of cancer and infectious diseases.

  12. B Cell Epitope-Based Vaccination Therapy

    Directory of Open Access Journals (Sweden)

    Yoshie Kametani

    2015-08-01

    Full Text Available Currently, many peptide vaccines are undergoing clinical studies. Most of these vaccines were developed to activate cytotoxic T cells; however, the response is not robust. Unlike vaccines, anti-cancer antibodies based on passive immunity have been approved as a standard treatment. Since passive immunity is more effective in tumor treatment, the evidence suggests that limited B cell epitope-based peptide vaccines may have similar activity. Nevertheless, such peptide vaccines have not been intensively developed primarily because humoral immunity is thought to be preferable to cancer progression. B cells secrete cytokines, which suppress immune functions. This review discusses the possibility of therapeutic antibody induction by a peptide vaccine and the role of active and passive B cell immunity in cancer patients. We also discuss the use of humanized mice as a pre-clinical model. The necessity of a better understanding of the activity of B cells in cancer is also discussed.

  13. Research progress on the therapeutic cancer vaccines and its application%治疗性肿瘤疫苗的研究及其应用进展

    Institute of Scientific and Technical Information of China (English)

    黄晨西; 高萍

    2015-01-01

    To eliminate cancer hazards to human health,the development of the therapeutic cancer vaccine has been given more and more attention.By contrast of tradition therapy,cancer immunotherapy take the advantage of being able to achieve target therapy and take modest harm to organism.Here,we first idiscussed the mechanisms of cancer immune escape,and reviewed the design principles of therapeutic cancer vaccine,as well as the latest research progress of therapeutic cancer vaccine and its application.%为了消除肿瘤对人类健康的危害,治疗性肿瘤疫苗的研发日益受到人们的重视.相对于传统治疗手段,肿瘤免疫治疗具有靶向性高、对机体伤害小的优点.本文首先对肿瘤的免疫逃脱机制进行了探讨,并对治疗性肿瘤疫苗的设计原则,以及各种治疗性肿瘤疫苗的最新研究进展以及应用进行了回顾,最后对肿瘤疫苗的发展进行了展望.

  14. Long-term clinical and immunological effects of p53-SLP (R) vaccine in patients with ovarian cancer

    NARCIS (Netherlands)

    Leffers, Ninke; Vermeij, Renee; Hoogeboom, Baukje-Nynke; Schulze, Ute R.; Wolf, Rinze; Hamming, Ineke E.; van der Zee, Ate G.; Melief, Kees J.; van der Burg, Sjoerd H.; Daemen, Toos; Nijman, Hans W.

    2012-01-01

    Vaccine-induced p53-specific immune responses were previously reported to be associated with improved response to secondary chemotherapy in patients with small cell lung cancer. We investigated long-term clinical and immunological effects of the p53-synthetic long peptide (p53-SLP (R)) vaccine in pa

  15. Immunogenicity and efficacy of an in-house developed cell-culture derived veterinarian rabies vaccine.

    Science.gov (United States)

    Kallel, Héla; Diouani, Mohamed Fethi; Loukil, Houssem; Trabelsi, Khaled; Snoussi, Mohamed Ali; Majoul, Samy; Rourou, Samia; Dellagi, Koussay

    2006-05-29

    The efficiency of an inactivated tissue culture rabies vaccine produced on BHK-21 cells, according to an in-house developed process, was evaluated and compared to a commercial cell-tissue culture vaccine (Rabisin). Fifteen experimental dogs from local common breed were duly conditioned during a quarantine period, then vaccinated via the subcutaneous route with 1 ml of either the tissue culture vaccine developed in-house or the commercial vaccine Rabisin. The immune response of each dog was monitored for 162 days. Serum-neutralizing antibodies titers to rabies virus were determined by the rapid fluorescent focus inhibition test (RFFIT) which confirmed the strong response of dogs to both vaccines except one dog in the Rabisin group. The dogs were then challenged in the masseter muscle with a rabies street virus of canine origin. All vaccinated dogs except the single dog in the Rabisin group that failed to respond to the vaccine, survived the challenge. In contrast, 80% of animals in the control non-vaccinated group, developed rabies and died. A field vaccine trial was also conducted: 1,000 local dogs living in field conditions received one subcutaneous dose of the locally developed vaccine. Serum neutralizing antibody titers to rabies virus was determined by RFFIT at days 0, 60 and 360. Mean rabies neutralizing antibody titers were equal to 0.786, 3.73 and 1.55 IU/ml, respectively. The percentage of dogs with a neutralizing rabies antibody titer higher than the 0.5 IU/ml mandated WHO threshold, was 30%, 91.4% and 87.5% at day 0, 2 months and 1 year post-vaccination, respectively. These data demonstrate the efficiency of the in-house developed vaccine produced on BHK-21 cells in both experimental and field conditions and support its use in dog mass vaccination campaigns.

  16. Recent advances in the development of subunit-based RSV vaccines.

    Science.gov (United States)

    Jaberolansar, Noushin; Toth, Istvan; Young, Paul R; Skwarczynski, Mariusz

    2016-01-01

    Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections causing pneumonia and bronchiolitis in infants. RSV also causes serious illness in elderly populations, immunocompromised patients and individuals with pulmonary or cardiac problems. The significant morbidity and mortality associated with RSV infection have prompted interest in RSV vaccine development. In the 1960s, a formalin-inactivated vaccine trial failed to protect children, and indeed enhanced pathology when naturally infected later with RSV. Hence, an alternative approach to traditional killed virus vaccines, which can induce protective immunity without serious adverse events, is desired. Several strategies have been explored in attempts to produce effective vaccine candidates including gene-based and subunit vaccines. Subunit-based vaccine approaches have shown promising efficacy in animal studies and several have reached clinical trials. The current stage of development of subunit-based vaccines against RSV is reviewed in this article.

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

    Science.gov (United States)

    Stewart Massad, L.; Evans, Charlesnika T.; Weber, Kathleen M.; D'Souza, Gypsyamber; Hessol, Nancy A.; Wright, Rodney L.; Colie, Christine; Strickler, Howard D.; Wilson, Tracey E.

    2015-01-01

    Purpose To describe changes in knowledge of cervical cancer prevention, human papillomavirus (HPV), and HPV vaccination among women at high risk for cervical cancer in the first five years after introduction of HPV vaccination. Methods In 2007, 2008–9, and 2011, women in a multicenter U.S. cohort study completed 44-item self-report questionnaires assessing knowledge of cervical cancer prevention, HPV, and HPV vaccination. Results across time were assessed for individuals, and three study enrollment cohorts were compared. Knowledge scores were correlated with demographic variables, measures of education and attention, and medical factors. Associations were assessed in multivariable models. Results In all, 974 women completed three serial questionnaires; most were minority, low income, and current or former smokers. The group included 652 (67%) HIV infected and 322 (33%) uninfected. Summary knowledge scores (possible range 0–24) increased from 2007 (12.8, S.D. 5.8) to 2008–9 (13.9, S.D. 5.3, P < 0.001) and to 2011 (14.3, S.D. 5.2, P < 0.0001 vs 2007 and < 0.04 vs 2008–9). Higher knowledge scores at first and follow-up administration of questionnaires, higher income, and higher education level were associated with improved knowledge score at third administration. Women not previously surveyed had scores similar to those of the longitudinal group at baseline. 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. PMID:25870859

  18. Scientific challenges and opportunities in developing novel vaccines for the emerging and developing markets: New Technologies in Emerging Markets, October 16th-18th 2012, World Vaccine Congress, Lyon.

    Science.gov (United States)

    Kochhar, Sonali

    2013-04-01

    Vaccines have had a major role in enhancing the quality of life and increasing life expectancy. Despite these successes and the development of new vaccine technologies, there remain multiple infectious diseases including AIDS, malaria and tuberculosis that require effective prophylactic vaccines. New and traditional technologies have a role in the development and delivery of the new vaccine candidates. The scientific challenges, opportunities and funding models for developing vaccines for low resource settings are highlighted here.

  19. Atopy and development of cancer

    DEFF Research Database (Denmark)

    Skaaby, Tea; Nystrup Husemoen, Lise Lotte; Roswall, Nina

    2014-01-01

    BACKGROUND: Atopy is the familial or personal propensity to develop IgE antibodies against environmental allergens. Atopy, theoretically, could both prevent and promote the development of cancer. However, evidence from epidemiologic studies has been inconclusive. OBJECTIVE: We investigated...... the longitudinal association between atopy and the incidence of total and specific types of cancers of 5 Danish population-based studies. METHODS: Atopy was defined as serum specific IgE positivity against inhalant allergens. A total of 14,849 persons were followed up prospectively by linkage to the Danish Cancer...... Registry. We used Cox regression analysis, and risk was expressed as hazard ratios (HR) (95% CIs) for persons with atopy versus those without atopy. RESULTS: There were 1919 incident cancers (median follow-up, 11.8 years). There were no statistically significant associations between atopy and risk of any...

  20. Current developments in avian influenza vaccines, including safety of vaccinated birds as food.

    Science.gov (United States)

    Swayne, D E; Suarez, D L

    2007-01-01

    Until recently, most vaccines against avian influenza were based on oil-emulsified inactivated low- or high-pathogenicity viruses. Now, recombinant fowl pox and avian paramyxovirus type 1 vaccines with avian influenza H5 gene inserts (+ or - N1 gene insert) are available and licensed. New technologies might overcome existing limitations to make available vaccines that can be grown in tissue culture systems for more rapid production; provide optimized protection, as a result of closer genetic relations to field viruses; allow mass administration by aerosol, in drinking-water or in ovo; and allow easier strategies for identifying infected birds within vaccinated populations (DIVA). The technologies include avian influenza viruses with partial gene deletions, avian influenza-Newcastle disease virus chimeras, vectored vaccines such as adenoviruses and Marek's disease virus, and subunit vaccines. These new methods should be licensed only after their purity, safety, efficacy and potency against avian influenza viruses have been demonstrated, and, for live vectored vaccines, restriction of viral transmission to unvaccinated birds. Use of vaccines in countries affected by highly pathogenic avian influenza will not only protect poultry but will provide additional safety for consumers. Experimental studies have shown that birds vaccinated against avian influenza have no virus in meat and minimal amounts in eggs after HPAI virus challenge, and that replication and shedding from their respiratory and alimentary tracts is greatly reduced.

  1. A Feasibility Study of Cyclophosphamide, Trastuzumab, and an Allogeneic GM-CSF-secreting Breast Tumor Vaccine for HER-2+ Metastatic Breast Cancer

    Science.gov (United States)

    Chen, G; Gupta, R; Petrik, S; Laiko, M; Leatherman, JM; Asquith, JM; Daphtary, MM; Garrett-Mayer, E; Davidson, NE; Hirt, K; Berg, M; Uram, JN; Dauses, T; Fetting, J; Duus, EM; Atay-Rosenthal, S; Ye, X; Wolff, AC; Stearns, V; Jaffee, EM; Emens, LA

    2014-01-01

    Granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting tumor vaccines are bioactive, but limited by disease burden and immune tolerance. Cyclophosphamide (CY) augments vaccine activity in tolerant neu mice and metastatic breast cancer (MBC) patients. HER-2-specific monoclonal antibodies (MAb) enhance vaccine activity in neu mice. We hypothesized that CY-modulated vaccination with HER-2-specific MAb safely induces relevant HER-2-specific immunity in neu mice and HER-2+ MBC patients. Adding both CY and the HER-2-specific MAb 7.16.4 to vaccination maximized HER-2-specific CD8+ T-cell immunity and tumor-free survival in neu transgenic mice. We therefore conducted a single arm feasibility study of CY, an allogeneic HER-2+ GM-CSF-secreting breast tumor vaccine, and weekly trastuzumab in 20 HER-2+ MBC patients. Primary clinical trial objectives were safety and clinical benefit (CB), in which CB represents complete response+partial response+stable disease. Secondary study objectives were to assess HER-2-specific T-cell responses by delayed type hypersensitivity (DTH) and intracellular cytokine staining. Subjects received three monthly vaccinations, with a boost 6-8 months from trial entry. This combination immunotherapy was safe, with CB rates at 6 months and 1 year of 55% (95% CI:32-77%, p=0.013) and 40% (95% CI:19-64%) respectively. Median progression-free survival (PFS) and overall survival (OS) were 7 (95% CI:4-16) and 42 months (95% CI:22-70) respectively. Increased HER-2-specific DTH developed in 7/20 subjects (of whom 4 had CB (95% CI:18-90)), with a trend toward longer PFS and OS in DTH responders. Polyfunctional HER-2-specific CD8+ T cells progressively expanded across vaccination cycles. Further investigation of CY-modulated vaccination with trastuzumab is warranted. (Clinicaltrials.gov identifier: NCT00399529) PMID:25116755

  2. Development of antifertility vaccine using sperm specific proteins

    Directory of Open Access Journals (Sweden)

    A H Bandivdekar

    2014-01-01

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

  3. Breast Cancer Vaccines Based on Dendritic Cells and the Chemokines

    Science.gov (United States)

    1998-07-01

    In: Cancer: Principles and Practice of Oncology . DeVita Jr VT, Hellman S, Rosenberg SA (eds.), JB Lippincott Co., Philadelphia, p. 293, 1993. 2...Alteration of signal transduction in T cells from cancer patients. In: Important Advances in Oncology 1995. DeVita Jr VT, Hellman S, Rosenberg SA (eds.), JB...Rosenberg SA: Cell transfer therapy: Clinical applications. In: Biologic Therapy of Cancer. DeVita Jr VT, Hellman S, Rosenberg SA (eds.), JB Lippincott

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

    Directory of Open Access Journals (Sweden)

    Peter Christiaan Soema

    2015-05-01

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

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

    NARCIS (Netherlands)

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

    1996-01-01

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

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

    NARCIS (Netherlands)

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

    2008-01-01

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

  7. Metronomic Cyclophosphamide and Methotrexate Chemotherapy Combined with 1E10 Anti-Idiotype Vaccine in Metastatic Breast Cancer

    Directory of Open Access Journals (Sweden)

    Jorge L. Soriano

    2011-01-01

    Full Text Available The use of low doses of cytotoxic agents continuously for prolonged periods is an alternative for the treatment of patients with metastatic breast cancer who have developed resistance to conventional chemotherapy. The combination of metronomic chemotherapy with therapeutic vaccines might increase the efficacy of the treatment. Twenty one patients with metastatic breast cancer in progression and a Karnosky index ≥60%, were treated with metronomic chemotherapy (50 mg of cyclophospamide orally daily and 2.5 mg of methotrexate orally bi-daily, in combination with five bi-weekly subcutaneous injections of 1 mg of aluminum hydroxide-precipitated 1E10 anti-idiotype MAb (1E10-Alum, followed by reimmunizations every 28 days. Five patients achieved objective response, eight showed stable disease and eight had disease progression. Median time to progression was 9,8 months, while median overall survival time was 12,93 months. The median duration of the response (CR+PR+SD was 18,43 months (12,20–24,10 months, being higher than 12 months in 76,9% of the patients. Overall toxicity was generally mild. Metronomic chemotherapy combined with 1E10-Alum vaccine immunotherapy might be a useful therapeutic option for the treatment of metastatic breast cancer due to its potential impact on survival and patient quality of live, low toxicity and advantages of the administration.

  8. Novel Method Of Preparing Vaccines | NCI Technology Transfer Center | TTC

    Science.gov (United States)

    This invention from the NCI Cancer and Inflammation Program describes methods to prepare vaccines for the treatment of human immunodeficiency virus (HIV) infections. The National Cancer Institute's Cancer and Inflammation Program seeks parties interested in licensing or collaborative research to further develop, evaluate, or commercialize novel methods of preparing vaccines.

  9. Skin vaccination against cervical cancer associated human papillomavirus with a novel micro-projection array in a mouse model.

    Directory of Open Access Journals (Sweden)

    Holly J Corbett

    Full Text Available BACKGROUND: Better delivery systems are needed for routinely used vaccines, to improve vaccine uptake. Many vaccines contain alum or alum based adjuvants. Here we investigate a novel dry-coated densely-packed micro-projection array skin patch (Nanopatch™ as an alternate delivery system to intramuscular injection for delivering an alum adjuvanted human papillomavirus (HPV vaccine (Gardasil® commonly used as a prophylactic vaccine against cervical cancer. METHODOLOGY/PRINCIPAL FINDINGS: Micro-projection arrays dry-coated with vaccine material (Gardasil® delivered to C57BL/6 mouse ear skin released vaccine within 5 minutes. To assess vaccine immunogenicity, doses of corresponding to HPV-16 component of the vaccine between 0.43 ± 0.084 ng and 300 ± 120 ng (mean ± SD were administered to mice at day 0 and day 14. A dose of 55 ± 6.0 ng delivered intracutaneously by micro-projection array was sufficient to produce a maximal virus neutralizing serum antibody response at day 28 post vaccination. Neutralizing antibody titres were sustained out to 16 weeks post vaccination, and, for comparable doses of vaccine, somewhat higher titres were observed with intracutaneous patch del