Dr Tamar Ben-Yedidia has more than 15 years of experience in the field of immunology, with specific expertise in the development of vaccines. She started her career with Biotechnology General Ltd (BTG; Rehovot, Israel), working on the development of a recombinant hepatitis B vaccine. She joined the Weizmann Institute of Science (Rehovot, Israel) in 1994 and, under the auspices of Professor Ruth Arnon in the Department of Immunology, worked on the design of a peptide-based vaccine against several pathogens, focusing on influenza. Dr Ben-Yedidia received her PhD from the Weizmann Institute after completion of her doctoral thesis entitled 'A Peptide-Based Vaccine Against Influenza'. She continued this work when she left the Weizmann Institute in 2005 to join BiondVax (Ness Ziona, Israel). She was involved in two European Consortium projects related to the evaluation of different approaches for vaccination in which leading laboratories in the field participated. She is often invited to address conferences around the world and has published around 20 refereed articles and invited reviews in various renowned scientific journals. In this interview, Dr Tamar Ben-Yedidia speaks to Commissioning Editor Duc Le.
Immunization represents the most effective approach to the prevention of hepatitis B virus infection and the long-term complications of chronic disease, including liver cancer and liver failure. Current vaccines require three doses to achieve maximal immunogenicity and fail to produce long-lasting protection in 5-10% of immune-competent individuals and in a much larger proportion of immune-compromised patients. Immunostimulatory DNA sequence (ISS) vaccine adjuvants, when combined with vaccine antigens, may increase immunogenicity and reduce the number of required doses to achieve this goal. 1018 ISS plus recombinant hepatitis B surface antigen has been demonstrated to achieve these goals in immune competent and vaccine-hyporesponsive populations without compromising recipient safety.
Recent terrorist attacks involving the use of Bacillus anthracis spores have stimulated interest in the development of new vaccines for anthrax prevention. Studies of the pathogenesis of anthrax and of the immune responses following infection and immunization underscore the pivotal role that antibodies to the protective antigen play in protection. The most promising vaccine candidates contain purified recombinant protective antigen. Clinical trials of one of these, recombinant protective antigen (rPA)102, are underway. Initial results suggest that rPA102 is well tolerated and immunogenic. Additional trials are necessary to identify optimal formulations and immunization regimens for pre- and postexposure prophylaxis. Future licensure of these and other candidate vaccines will depend on their safety and immunogenicity profiles in humans, and their ability to confer protection in animal models of inhalational anthrax.
This review will focus on DNA vaccine approaches for the prevention or treatment of cancer and its complications. DNA vaccine therapies are a relatively novel method of cancer treatment with the goal to induce immunity against tumor-associated antigens. Both viral and nonviral vaccines have been tested in preclinical and clinical models with variable success. However, the development of new delivery methods, such as electroporation, as well as the use of agents that improve antigen uptake or presentation, and the optimization of the transgene sequences, are overcoming historical drawbacks. Efficacy and safety issues of the in vivo use of DNA-based vaccines, as well as data from preclinical and recent clinical studies, are discussed. Novel developments will improve clinical efficacy, with the potential for DNA vaccination to enter in to the arsenal of cancer therapies in the near future.
Human papillomavirus infection causes cervical cancer, a significant portion of anal, genital and oropharyngeal cancers, genital warts and recurrent respiratory papillomatosis. In June 2006, a quadrivalent human papillomavirus-6/11/16/18 vaccine (GARDASIL/SILGARD®; Merck, NJ, USA) was licensed in the USA; subsequent approval has been granted in the EU (September 2006). It has since been approved in 121 countries with over 74 million doses distributed globally as of March 2011.
The development of adjuvants will represent a major challenge for this century. Indeed the need for safer vaccines leads to the development of a new generation of antigens like synthetic peptide, recombinant proteins or even vectored DNA. However, this is to the detriment of their immunogenicity. The addition of adjuvant is becomes necessary to enhance immune responses and improve vaccine potency. However, adjuvants can be responsible for the apparition of secondary reactions and they must be adapted according to various criteria such as the route of immunization, the type of the immune response, the duration of immunity, or the quality of the antigen, in order to get the best balance between efficacy and safety.
The severe combined immunodeficient (SCID) mouse has no adaptive immunity, lacking mature T and B cells in the peripheral blood or the lymphoid organs. It has been used extensively in biomedical research as a valuable translational model for xeno-engraftment of human tissues and cells. This review focuses on the engraftment of human peripheral blood cells and tissues in SCID mice, as well as in the newly established and more permissive SCID mice deficient in the IL-2 receptor gamma-chain. Human immune responses could be elicited and assessed in these humanized SCID mice upon vaccination or sensitization with allogeneic tissues. A translational model is proposed to attain preclinical data for testing human vaccines.
Routine use of pertussis vaccines has diminished the incidence of this disease but has not eliminated the pathogen. Pertussis remains a significant cause of disease in both very young infants and in the adolescent and adult populations. Acellular pertussis vaccines have fewer adverse reactions compared with whole-cell pertussis vaccines. Although efficacious against severe disease, current vaccines may not be as efficacious against milder forms of infection. New methodologies for understanding disease pathogenesis, immune responses and vaccine development are needed to effectively interrupt continued transmission of this pathogen.
Virus-like particles (VLPs) are multiprotein structures that mimic the organization and conformation of authentic native viruses but lack the viral genome, potentially yielding safer and cheaper vaccine candidates. A handful of prophylactic VLP-based vaccines is currently commercialized worldwide: GlaxoSmithKline's Engerix (hepatitis B virus) and Cervarix (human papillomavirus), and Merck and Co., Inc.'s Recombivax HB (hepatitis B virus) and Gardasil (human papillomavirus) are some examples. Other VLP-based vaccine candidates are in clinical trials or undergoing preclinical evaluation, such as, influenza virus, parvovirus, Norwalk and various chimeric VLPs. Many others are still restricted to small-scale fundamental research, despite their success in preclinical tests. This article focuses on the essential role of VLP technology in new-generation vaccines against prevalent and emergent diseases. The implications of large-scale VLP production are discussed in the context of process control, monitorization and optimization. The main up- and down-stream technical challenges are identified and discussed accordingly. Successful VLP-based vaccine blockbusters are briefly presented concomitantly with the latest results from clinical trials and the recent developments in chimeric VLP-based technology for either therapeutic or prophylactic vaccination.
The 11th Annual Conference on Vaccine Research, hosted by the National Foundation for Infectious Disease, attracted approximately 450 leaders in the fields of epidemiology, health economics, immunology and vaccinology, making it the largest scientific meeting devoted exclusively to vaccine research and technology. The conference highlighted recent advancements in vaccine design, including the discovery of new adjuvants, cytokines and regulatory pathways. Other topics included a comprehensive overview of the development and uses of cutaneous vaccination and a discussion of recently licensed vaccines against the human papillomavirus, herpes zoster virus, meningococcal disease and rotavirus and a discussion on the importance of redesigning and increasing the coverage of the influenza vaccine. Keynote remarks were provided by the demographer and economist David E Bloom (Harvard School of Public Health, USA), who argued that traditional economic evaluations of vaccine interventions have failed to account for the full range of benefits that can accrue from vaccination. These benefits are substantial in size and potentially decisive with respect to the bottom-line results of benefit-cost calculations.
The 12th Annual Conference on Vaccine Research, hosted by the National Foundation for Infectious Disease, attracted approximately 450 leaders in the fields of epidemiology, health economics, immunology and vaccinology, making it the largest scientific meeting devoted exclusively to vaccine research and technology. The conference highlighted recent issues in vaccine safety, including the history and design of a vaccine for rotavirus. Other topics included discussions of the synergies between veterinary and human vaccine development, updates on the development of vaccines for tuberculosis and malaria, and a comprehensive overview of immunization initiatives and goals for extending coverage of new and underused vaccines. Keynote remarks were provided by David Salisbury (Department of Health, London, UK) who outlined the aims and objectives of the Global Immunization Vision and Strategy (GIVS), an agenda created by the WHO and UNICEF. Salisbury highlighted the four primary aims of GIVS: immunize more people against more diseases, introduce a range of newly available vaccines and technologies, integrate other critical health interventions with immunization, and manage vaccination programs within the context of global interdependence. The GIVS initiative spans the time period of 2006-2015.
The introduction of a 7-valent pneumococcal conjugate vaccine (PCV-7) into the routine childhood vaccination schedule has been shown to be effective in preventing invasive pneumococcal disease (IPD), pneumonia, otitis media and meningitis in infants and young children as determined by epidemiological surveillance studies. There has been a rise in IPD due to nonvaccine serotypes; however, this rise is small compared with the overall reduction in IPD. Non-PCV-7 serotypes and vaccine-related serotypes, such as serotypes 1, 5, 7F, 6A and 19A, have also been reported to cause IPD in some parts of the world where morbidity and mortality from pneumococcal disease are higher. An investigational 13-valent pneumococcal conjugate vaccine (PCV-13) uses CRM(197) as a carrier, similar to the current PCV-7, and covers serotypes 1, 3, 5, 6A, 7F and 19A, in addition to the serotypes of PCV-7 (serotype 4, 6B, 9V, 14, 18C, 19F and 23F). PCV-13 is safe and well tolerated with other pediatric vaccines in infants according to clinical trials. IgG anticapsular polysaccharide-binding concentrations and opsonophagocytic assay responses are similar and noninferior between PCV-13 and PCV-7 and, according to immunogenicity studies, PCV-13 has more potential to protect against pneumococcal diseases with the additional six serotypes. With the addition of these new serotypes, it could be possible to cover potential pneumococcal serotypes causing IPD throughout the world. The cost of the vaccine, its length of duration, optimal scheduling, combination and boosting with PCV-7 are still unresolved issues. Assessment of the vaccine's effectiveness and efficacy following potential licensure will require carefully designed cohort and case-control studies that can assess the indirect effects of PCV-13.
Pneumococcal polysaccharide-protein conjugate vaccines (PCVs) generally protect against vaccine-serotype-specific pneumococcal disease. Additional serotypes included in the new 13-valent PCV (PCV-13) formulation and not in the first-generation 7-valent PCV (PCV-7) formulations are 1, 3, 5, 6A, 7F and 19A. Importantly, serotype 1 is associated with a high proportion and burden of pneumococcal disease in low-income countries, whilst serotype 19A emerged as the dominant disease-causing serotype following widespread PCV-7 immunization in the USA. In this article we present the available data on the immunogenicity and safety of PCV-13 in infants and children. Noninferiority studies indicate a similar immunogenicity profile between PCV-13 and PCV-7 recipients against most of the common serotypes. A favorable immunogenicity profile was also observed for at least five of the additional serotypes in PCV-13. An attenuated anamnestic response to serotype 3 was reported in five out of 14 studies. PCV-13 was demonstrated to have a similar acceptable safety profile to PCV-7 and no interference in immunogenicity of other concomitantly administered childhood vaccines was observed among PCV-13 recipients.
Cancer vaccines have demonstrated clinical benefit, however greater efficacy could be achieved by enhancing their immunogenicity. Owing to cancer vaccines depending on uptake and cross-presentation of tumor antigens by antigen-presenting cells (APCs), we hypothesized that greater immunogenicity would accompany strategies that direct antigen to APC-expressed mannose receptors, initiating a pathway increasing class I and II presentation to T cells. CDX-1307 consists of a human monoclonal antibody targeting the mannose receptor, fused to the human chorionic gonadotropin-β chain (hCG-β), a tumor antigen frequently expressed by epithelial cancers including bladder cancer. In Phase I studies of cancer patients, CDX-1307 was well tolerated and induced significant hCG-β-specific cellular and humoral immune responses when co-administered with GM-CSF and the Toll-like receptor agonists resiquimod and poly-ICLC. An ongoing Phase II trial evaluates CDX-1307 in patients with newly diagnosed, resectable, hCG-β-expressing bladder cancer, where low tumor burden and early intervention may provide greater potential for benefit.
Continuously evolving avian influenza viruses pose a constant threat to the human public health. In response to this threat, a number of pandemic vaccine candidates have been prepared and evaluated in animal models and clinical trials. This review summarizes the data from the development and preclinical and clinical evaluation of pandemic live attenuated influenza vaccines (LAIV) based on Russian master donor virus A/Leningrad/134/17/57. LAIV candidates of H5N1, H5N2, H7N3, H1N1 and H2N2 subtypes were safe, immunogenic and protected animals from challenge with homologous and heterologous viruses. Clinical trials of the pandemic LAIVs demonstrated their safety and immunogenicity for healthy adult volunteers. The vaccine viruses were infectious, genetically stable and did not transmit to unvaccinated contacts. In addition, here we discuss criteria for the assessment of pandemic LAIV immunogenicity and efficacy necessary for their licensure.
Invasive meningococcal disease is a global public-health concern, with infants and adolescents bearing the majority of the disease burden. Vaccination is the most rational strategy to prevent meningococcal disease. Control of serogroup C disease has largely been achieved by the introduction of glycoconjugate meningococcal C vaccines, initially in the UK in 1999, and subsequently in several other countries. The recent licensure of a quadrivalent glycoconjugate vaccine against serogroups A, C, Y and W-135 in the USA and Canada has broadened protection against Neisseria meningitidis in 2-55 year olds. The investigational quadrivalent meningococcal serogroup A, C, Y and W-135 glycoconjugate vaccine (MenACYW-CRM197), which is immunogenic from infancy, has the potential to extend protection to the most vulnerable age group. This article discusses this novel quadrivalent vaccine formulation and its potential to control invasive disease caused by N. meningitidis serogroups A, C, Y and W-135.
Invasive disease due to Neisseria meningitidis continues to cause debility and death worldwide in otherwise healthy individuals. Disease epidemiology varies globally, but most cases are due to serogroups A, B, C, W-135 or Y. MenactraTM (MCV-4), a quadrivalent, meningococcal diphtheria-conjugate vaccine against serogroups A, C, Y, and W-135, was licensed in the USA for individuals 11-55 years of age. Published results of clinical trials demonstrated robust immune responses that correlate with indicators of protection. MCV-4-induced antibody persist for up to 3 years after administration and anamnestic responses to revaccination. The vaccine was well tolerated; the most common reactions were transient, mild injection-site reactions and headache. MCV-4 should provide significant clinical benefits in the future.
Meningococcal disease remains a global public health concern despite the wide availability of polysaccharide and polysaccharide-protein conjugate vaccines. The latter often afford a greater duration and scope of protection compared with the former. A novel quadrivalent meningococcal conjugate vaccine, Menveo(®) (MenACWY-CRM; Novartis Vacines, Bellaria-Rosia, Italy) has recently been licensed in Europe, the USA, Canada and other countries to protect adolescents and adults against disease caused by serogroups A, C, W-135 and Y. MenACWY-CRM has an immunogenicity and tolerability profile in adolescents and adults supported by an extensive clinical development program. MenACWY-CRM induced immune responses that were at least as good as those induced by Menactra(®) (MenACWY-D; Sanofi Pasteur [Swiftwater, PA, USA]), a quadrivalent meningococcal polysaccharide-protein conjugate vaccine) against serogroups A, C, W-135 and Y. Immune responses were also observed in a population of subjects 56-65 years of age. Published information also shows immunogenicity in infants, toddlers and children. Tolerability outcomes were similar for MenACWY-CRM, MenACWY-D and a plain polysaccharide quadrivalent vaccine against meningococcal serogroups A, C, W-135 and Y. Given its potential for protecting infants and persons over 55 years of age, MenACWY-CRM offers promise to fulfil an unmet global need for preventing invasive meningococcal disease in vulnerable populations for which no vaccine is available.
Cervical cancer is the third most common cancer in women worldwide and often affects women under 40 years of age with young families. Vaccination against HPV is a major advancement, as it offers primary prevention against the infectious agent that is the main cause of the disease. The bivalent AS04-adjuvanted prophylactic HPV vaccine provides high efficacy against disease associated with HPV 16 and 18, as well as significant cross-protection against some HPV types not included in the vaccine. Protection against HPV 45 may be particularly important, as it is relatively more common in adenocarcinoma. The vaccine's antibody response profile suggests a long duration of immunity. Safety data have been reassuring, which is not unexpected, given that the vaccine is composed of virus-like particles, rather than being a live-virus vaccine.
Owing to their low reactogenicity, confirmed efficacy and availability in combination vaccines, acellular pertussis (aP)-inactivated poliovirus (IPV) combined vaccines are now included in various national immunization programs worldwide. We provide an overview of 16 years of clinical experience with a diphtheria (D), tetanus (T), aP, IPV and Haemophilus influenzae type b (Hib) polysaccharide conjugated to tetanus protein (PRP∼T) combined vaccine (DTaP-IPV//PRP∼T - Pentaxim, Sanofi Pasteur, France). Good immunogenicity has been demonstrated after primary vaccination with Pentaxim, regardless of the population ethnicity and primary vaccination schedule. A booster vaccination in the second year of life also resulted in a high immune response for each antigen. Furthermore, 10 years of national surveillance in Sweden has demonstrated the effectiveness of Pentaxim in controlling pertussis. As is the case for other aP-containing combined vaccines, Pentaxim is well tolerated, with the safety profile being better than for whole-cell pertussis-containing combination vaccines for primary and booster vaccinations.
Failure of the immune system to launch a strong and effective immune response to high-risk HPV is related to viral persistence and the development of anogenital (pre)malignant lesions such as vulvar intraepithelial neoplasia (VIN). Different forms of immunotherapy, aimed at overcoming the inertia of the immune system, have been developed and met with clinical success. Unfortunately these, in principal successful, therapeutic approaches also fail to induce clinical responses in a substantial number of cases. In this review, the authors summarize the traits of the immune response to HPV in healthy individuals and in patients with HPV-induced neoplasia. The potential mechanisms involved in the escape of HPV-induced lesions from the immune system indicate gaps in our knowledge. Finally, the interaction between the immune system and VIN is discussed with a special focus on the different forms of immunotherapy applied to treat VIN and the potential causes of therapy failure. The authors conclude that there are a number of pre-existing conditions that determine the patients' responsiveness to immunotherapy. An immunotherapeutic strategy in which different aspects of immune failure are attacked by complementary approaches, will improve the clinical response rate.
The Human Vaccines Project is a bold new initiative, with the goal of solving the principal scientific problem impeding vaccine development for infectious diseases and cancers: the generation of specific, broad, potent and durable immune responses in humans. In the July 2014 workshop, 20 leaders from the public and private sectors came together to give input on strategic business issues for the creation of the Human Vaccines Project. Participants recommended the Project to be established as a nonprofit public-private partnership, structured as a global R&D consortium closely engaged with industrial partners, and located/affiliated with one or more major academic centers conducting vaccine R&D. If successful, participants concluded that the Project could greatly accelerate the development of new and improved vaccines, with the potential to transform disease prevention in the 21st century.
Persistent infection with oncogenic human papillomavirus (HPV)-16 and -18 accounts for over 70% of all cases of cervical cancer. Vaccination against these HPV types has become a reality. This article discusses the latest data available for Cervarix (GlaxoSmithKline Biologicals), an AS04-adjuvanted HPV-16/18 vaccine, and considers immunological factors important in vaccine effectiveness. High and sustained HPV-16 and -18 antibody levels have now been observed together with 100% vaccine efficacy in preventing HPV-16/18-related persistent infections and cervical intraepithelial neoplasia grade 2 and above, up to 6.4 years after first vaccination. Significant crossprotection against incident and persistent infection has been observed, notably against HPV-45, the third most prevalent HPV type in cervical cancer. An integrated safety summary of Phase II/III trials has shown that GlaxoSmithKline's HPV-16/18 AS04-adjuvanted vaccine is generally safe. Further studies will reveal the full duration and extent of the immune response and protection induced by Cervarix in broad populations and age ranges of women.
Malaria is responsible for approximately 5 billion clinical episodes, 500 million cases of morbidity, 10–20 million cases of severe disease and 1–3 million deaths each year [3,4,101]. An effective vaccine against malaria is considered by many to be the best hope of reducing the tremendous public health burden of this disease. It is apparent that significant advances have been made in understanding mechanisms of immunity, identifying target antigens, developing platform technologies, and designing and testing candidate vaccines in preclinical models and clinical trials. Although many challenges are yet to be overcome, there is considerable optimism in the field that the development of an effective malaria vaccine is not only feasible but is highly likely.
Since the creation by the manufacturer in 1993, of an electronic pharmacovigilance database for all spontaneous, voluntary reports of adverse events (AEs) after vaccination, 276 million doses of Stamaril® have been distributed worldwide. We review this database for the safety of Stamaril® with emphasis on yellow fever (YF) vaccine associated acute viscerotropic and neurotropic diseases, anaphylaxis and on specific at risk groups: elderly adults, pregnant and lactating women and the immunosuppressed. Findings confirm that the vaccine's safety profile in routine practice is favorable and consistent with the summary of product characteristics. Estimated reporting rates of serious adverse events associated after Stamaril® vaccination are lower than the previously published and widely cited estimates of the worldwide reporting rate for YF vaccines in general. These data provide important additional information for the prescribers in assessing the risks and benefits associated with the use of Stamaril® in individuals exposed to YF virus.
The need to enhance the immunogenicity of purified subunit antigens has prompted the development of several new adjuvants. However, many of these new molecules have demonstrated a reactogenicity profile that is not suitable for their inclusion in vaccines for human use. In this context, the adjuvant emulsion MF59 has been developed, tested in combination with different antigens in several animal models and subsequently evaluated in humans. Clinical trials with several MF59-adjuvanted vaccines have been performed in different age groups (from newborns to the elderly) and have shown an increased immunogenicity of coadministered antigens, associated with a high level of safety and tolerability. MF59 has been the first adjuvant to be licensed for human use after alum and, as part of an enhanced influenza vaccine for the elderly, is now available in the marketplace of several countries worldwide.
Epidemics of severe dehydrating cholera are on the increase in resource-limited settings around the world. Adults, children and young infants are all at risk of these infections. Considerable efforts have been made for the development of safe and efficacious oral cholera vaccines over the last three decades. Whole-cell-inactivated as well as live oral cholera vaccines have been developed and tested in different field settings to determine the efficacy and/or effectiveness of such vaccines for reducing life-threatening disease. This review follows the trail of the development of CholeraGarde, a live-attenuated Vibrio cholerae O1 vaccine candidate of the El Tor biotype and Inaba serotype. CholeraGarde, also well known as Peru-15, was derived from V. cholerae O1 strain C6709, a clinical isolate from Peru. The vaccine has now been tested in over 500 individuals, adults and children and shows a good safety and immunogenicity profile. At a dose of around 10(8) CFU, it is immunogenic in adults in the USA, as well as in adults, children and infants in Bangladesh. The vaccine has been tested in infants of 9 months of age where a single 10(8) CFU dose was safe and immunogenic while a tenfold lower dose was not. Excretion of the strain was higher in adults in the USA and low in Bangladeshi participants in all age groups. Phase II studies of CholeraGarde are ongoing in cholera-endemic countries to concomitantly administer it to infants with the parenteral measles vaccine. Studies on HIV-positive individuals are also ongoing to determine safety, immunogenicity and contraindications, if any. Phase III studies are being targeted to determine the protective efficacy of CholeraGarde and for further development of a single-dose vaccine that will protect infants and also other age groups from endemic and epidemic cholera.
Tumor associated antigen (TAA)-based therapeutic vaccines have great potential as a safe, practical, and cost-efficient alternative to standard treatments for cancer. Clinical efficacy of TAA-based vaccines, however, has yet to be realized and will require adjuvants with pleiotropic functions on immune cells. Such adjuvants need not only to generate/boost T cell responses, but also reverse intrinsic/extrinsic tumor immune evasion mechanisms for therapeutic efficacy. This review focuses on a novel agonistic ligand, SA-4-1BBL, for 4-1BB costimulatory receptor as an adjuvant of choice because of its ability to: i) serve as a vehicle to deliver TAAs to dendritic cells (DCs) for antigen uptake and cross-presentation to CD8(+) T cells; ii) augment adaptive Th1 and innate immune responses; and iii) overcome various immune evasion mechanisms, cumulatively translating into therapeutic efficacy in preclinical tumor models.
Prior to the introduction of rotavirus vaccines in 2006, rotavirus was the leading cause of severe gastroenteritis among US children <5 years of age. In the first 7 years of vaccine use, both recommended rotavirus vaccines (RotaTeq [RV5] and Rotarix [RV1]) have been shown to be highly effective in preventing outcomes of severe disease in US children in a variety of settings. In addition, substantial decreases in severe diarrheal disease in US children, exceeding the level expected based on vaccine coverage, as well as the extension of benefits to older age groups ineligible for vaccination have demonstrated both the direct and indirect impacts of vaccination in the USA.
Vaccines for prevention or treatment of infectious diseases are biological products that are regulated by the Office of Vaccines Research and Review in the Center for Biologics Evaluation and Research of the US FDA. The legal framework for the regulation of vaccines derives primarily from Section 351 of the Public Health Service Act and from certain sections of the Federal Food, Drug and Cosmetic Act (FFD & C Act). The FDA Amendments Act of 2007 (FDAAA 2007) includes extensive modifications to the FFD & C Act. This article provides an overview of the review process for preventive vaccines and highlights applicable statutory provisions. In addition, this article will discuss changes in the pre-and post-licensure evaluation process for preventive and therapeutic infectious disease vaccines since implementation of the FDAAA 2007.
This review elucidates state-of-the-art clinical studies on active specific immunotherapy with tumor vaccines. It refers solely to randomized studies and has a special focus on patient's survival, the most important parameter for any therapy. Of special interest, from a tumor immunological point of view, is a comparison between the results obtained with allogeneic tumor cell-derived vaccines and those obtained with autologous tumor cell-derived vaccines. Overall, autologous vaccines have given better results than allogeneic vaccines. Random mutations in cancer generate unique antigens in each individual case. The superiority of autologous vaccines suggests that unique tumor-associated antigens are particularly important in generating responsive T cells for a therapeutic effect.
The 4th International Workshop in Vaccine Adjuvants and Parasitic Vaccines (Adjuvant 2008), hosted by the Cuban Society for Immunology, attracted approximately 70 scientists from 22 countries. The meeting goal was mainly to share recent progress and discuss future challenges regarding vaccine adjuvants for the development of mucosal vaccines, as well as antiparasitic vaccines. Five keynote addresses, 21 oral presentations and 28 posters were presented, and the meeting was ended with a 'hot-topic' session discussing future challenges. This article highlights the most important issues discussed.
The Bangkok International Conference on Avian Influenza 2008 was organized by the National Center for Genetic Engineering and Biotechnology of Thailand. The Center has been playing an active role in the organization of research projects and knowledge management in preparation for an influenza pandemic since the beginning of the H5N1 avian influenza (AI) outbreak in the region in 2004. The timing of the conference, January 23rd, coincided with the 2004 announcement of the first outbreak in the country, marking the fourth year of widespread AI outbreaks in this region. In this 4-year period, progresses have been made scientifically and politically. Nevertheless, AI is still a major threat to us all. At the opening ceremony of the conference, Yongyuth Yuthavong, the Minister of Science and Technology of Thailand, emphasized that we are all together in the global village in this AI crisis and that we have to share information and materials and work together in the fight against this enemy of mankind.
Pandemic H1N1 influenza presented a significant threat to vulnerable immunocompromised hosts. Vaccination provided the best method of prevention, both for individuals and for herd immunity. Numerous studies have shown that the antibody response to pandemic H1N1 2009 influenza vaccine in adult organ transplant patients is diminished compared with normal hosts. Techniques to improve response to influenza vaccination, including multiple doses, use of adjuvants, different delivery methods and doses have been investigated in transplant patients. The recent article in Transplant International by Felldin et al. evaluating the humoral immune response to two serial doses of pandemic H1N1 2009 influenza vaccine in adult organ transplant recipients is reviewed.
The World Influenza conference comprised numerous plenary sessions and some panel discussions. The highlights of the meeting were the novel approaches to vaccine developments, particularly the use of live-attenuated viruses and baculovirus- or bacteriophage-derived virus-like particles as delivery vectors. Improvements in antigenicity have been demonstrated by thoroughly understanding the biology of the influenza virus; in particular, understanding which residues within the hemagglutinin protein correspond with plaque morphology in cell culture. At least two different bioinformatic approaches were discussed for the rationale design of peptide vaccines; these are naturally at a very early stage but data look promising. We were reminded by several presenters that although we were in the midst of a pandemic caused by the H1N1 swine-derived influenza strain, avian influenza strains were still circulating, and some were predicting more widespread infection with these strains in the future.
The Informa Life Sciences vaccines conference is an annual meeting of a relatively small number of academics and industrialists. It is split into three concurrent sessions covering vaccine discovery, quality and manufacturing. Although there were many presentations of merit, only a few will be discussed here, including the plenary speeches on adjuvants and influenza.