Global HIV Vaccine Enterprise Research Articles

Defining the objectives of the AIDS vaccine for Asia network: report of the WHO-UNAIDS/Global HIV vaccine enterprise regional consultation on expanding AIDS vaccine research and development capacity in Asia

An important meeting titled “Defining the Objectives of the AIDS Vaccine Asian Network (AVAN)” was held 22–24 February 2009, in Beijing. This report describes the outcomes of this meeting. The meeting was jointly organised by the World Health Organization (WHO), the Joint United Nations Programme on HIV/AIDS (UNAIDS) and the Global HIV Vaccine Enterprise (GHVE) Regional Consultation on Expanding AIDS Vaccine Research and Development Capacity in Asia. Sixty-eight participants (Supplementary Digital Content 1) and observers gathered together from 16 countries including Australia, Cambodia, China, France, India, Indonesia, Japan, the Netherlands, the Philippines, the Russian Federation, Singapore, Sweden, Switzerland, Thailand, the United States of America and Viet Nam. The meeting was highly relevant for the Asian region at a time when the HIV epidemic is still rampant despite concerted efforts by governments, communities, scientists and key stakeholders to stem its impact and advance. A great deal of work has been undertaken towards an AIDS vaccine over the past 15 years and the region has the essential assets to move the agenda forward. Genesis of the 2009 Beijing meeting In 1998, the first Asian meeting specifically devoted to AIDS vaccine research and development was convened by WHO-UNAIDS and the Japanese National Institute of Infectious Diseases (NIID) in Tokyo, Japan. In 2006, the regional strategy concept was revisited at the first WHO-UNAIDS regional consultation, Expanding Capacity and Accelerating AIDS Vaccine Development in Asia, hosted and co-organized by the University of Hokkaido, Sapporo, Japan. The 7 recommendations of the 2006 Sapporo meeting were to: First, create forums to facilitate interactions between funders and discuss funding opportunities, funding streams and funder capabilities. Second, facilitate linkages between research and development (R&D), innovation and discovery, in particular in emerging countries with strong innovation capacity, such as China, India and Thailand, and clinical trial capacity and production. Third, provide a forum for coordination of regional expertise, capacity building, and technical assistance. Fourth, promote advocacy and communication support for region-specific strategies. Fifth, contribute to and promote the implementation of the Scientific Strategic Plan of the GHVE. Sixth, prepare for future deployment of a vaccine by discussing regional approaches to ensure access, delivery capacity, demand estimates, epidemiology, vaccine characteristics, and strategies for delivery. Seventh, create a regional harmonization or regional authority for regulatory interactions, including regional licensure review and regional ethics committees with an initial ‘core’ working group. To effectively implement and further facilitate the recommendation to develop an ongoing forum for coordination of regional expertise, capacity building and technical assistance, the establishment of AVAN was proposed. In February 2009, the Chinese AIDS Vaccine Initiative (CAVI), GHVE and WHO-UNAIDS convened a follow-up meeting in Beijing, China to speed up implementation of recommendations of the Sapporo consultation.

The future of HIV vaccine research and the role of the Global HIV Vaccine Enterprise

This review covers the role of the Global HIV Vaccine Enterprise (the Enterprise), an alliance of independent organizations committed to development of a safe and effective HIV vaccine. It discusses the history, impact on the field, and future directions and initiatives of the alliance in the context of recent progress in HIV vaccine research and development. Significant progress has been made in the field since the release of the 2005 Scientific Strategic Plan (the Plan) of the Enterprise. Over the last year, the Enterprise embarked on an impact assessment of the 2005 Plan and the development of the 2010 Plan. Enterprise Working Groups identified key priorities in the field, several of which are discussed in this review, including changing the nature, purpose and process of clinical trials, increasing and facilitating data sharing, and optimizing existing and mobilizing new resources. This time is an important moment in HIV vaccine research. New clinical trial and laboratory results have created new opportunities to advance the search for an HIV vaccine and reinvigorated the field. The Enterprise will publish its 2010 Plan this year, providing a framework for setting new priorities and directions and encouraging new and existing partners to embark on a shared scientific agenda.

P15-20. Developing a national policy agenda for the Canadian HIV vaccine initiative

Background The Canadian HIV Vaccine Initiative (CHVI) is a five-year initiative between the Government of Canada and the Bill & Melinda Gates Foundation, and it represents a significant Canadian contribution to the Global HIV Vaccine Enterprise that seeks to accelerate the development of safe, effective, affordable and globally accessible HIV vaccines. A national HIV vaccines policy agenda is currently being developed as one measure to contribute to domestic and international HIV vaccines policy-related efforts.

P15-23. Community engagement strategies in the Canadian HIV vaccine initiative

Background The Canadian HIV Vaccine Initiative (CHVI) is a five-year initiative between the Government of Canada and the Bill & Melinda Gates Foundation, and it represents a significant Canadian contribution to the Global HIV Vaccine Enterprise that seeks to accelerate the development of safe, effective, affordable and globally accessible HIV vaccines. Through its Community and Social Dimensions program area, the CHVI has implemented strategies to engaging community-based AIDS organizations (CBAO's) through dialogue/consultation and a new HIV vaccine Community Initiatives Fund.

African AIDS Vaccine Programme for a Coordinated and Collaborative Vaccine Development Effort on the Continent

Nearly 30 years after the first cases of AIDS were reported [1] and HIV identified as the causative agent, Africa today bears a disproportionate burden of the disease. Sub-Saharan Africa has just over 10% of the world's population but is home to more than 65% of the 33 million people in the world estimated to be living with HIV/AIDS. The annual rate of new infections continues to rise, with an estimated 2.5 million people newly infected in 2007 [2]. Although newer initiatives aimed at providing universal access to antiretroviral therapy in Africa are ongoing, most Africans receive neither treatment nor adequate care [3]. Relatively few HIV-infected patients in sub-Saharan Africa (about 1 million) are currently receiving antiretroviral treatment [4], and many more new cases are occurring each year [2]. It is thus evident that treatment alone will not control the spread of the disease and that a vaccine is our best hope of halting this pandemic. In the history of infectious diseases, effective vaccines are critical public health tools to control and prevent diseases. Developing an effective HIV vaccine is proving to be one of the greatest challenges in biomedical research. The need for a simple, safe, effective, affordable, and equitably distributed preventive HIV vaccine to complement existing HIV/AIDS prevention, treatment, and care programs is greater than ever. It is probable that vaccines will form part of future innovative interventions including microbicides and circumcision, used in conjunction with other more traditional prevention interventions. Summary Points The AIDS pandemic continues to be the most serious public health challenge facing the world today, and Africa bears an overwhelming proportion of infections, with unprecedented medical and socioeconomic consequences. The best hope to end the AIDS pandemic remains the development of an effective HIV vaccine, and its distribution to all communities. The African AIDS Vaccine Programme (AAVP), formed in 2000, is a network of African HIV vaccine stakeholders, led by Africans across the continent, with a vision of an African continent without AIDS. AAVP supports and represents the diverse African communities involved in HIV vaccine research and development (R&D), and is an important unified voice for African stakeholders. This paper describes what AAVP is, what it does, and its impact, successes, and challenges. Finally, we discuss where AAVP is heading to harmonize with the Global HIV Vaccine Enterprise and the dynamic HIV vaccine research field.

Antibody-Based HIV-1 Vaccines: Recent Developments and Future Directions

The Global HIV Vaccine Enterprise convened a two-day workshop in May of 2007 to discuss humoral immune responses to HIV and approaches to design vaccines that induce viral neutralizing and other potentially protective antibody responses. The goals of this workshop were to identify key scientific issues, gaps, and opportunities that have emerged since the Enterprise Strategic Plan was first published in 2005 [1], and to make recommendations that Enterprise stakeholders can use to plan new activities. Most effective viral vaccines work, at least in part, by generating antibodies that inactivate or neutralize the invading virus, and the existing data strongly suggest that an optimally effective HIV-1 vaccine should elicit potent antiviral neutralizing antibodies. However, unlike acute viral pathogens, HIV-1 chronically replicates in the host and evades the antibody response. This immune evasion, along with the large genetic variation among HIV-1 strains worldwide, has posed major obstacles to vaccine development. Current HIV vaccine candidates do not elicit neutralizing antibodies against most circulating virus strains, and thus the induction of a protective antibody response remains a major priority for HIV-1 vaccine development. For an antibody-based HIV-1 vaccine, progress in vaccine design is generally gauged by in vitro assays that measure the ability of vaccine-induced antibodies to neutralize a broad spectrum of viral isolates representing the major genetic subtypes (clades) of HIV-1 [2]. Although it is not known what magnitude and breadth of neutralization will predict protection in vaccine recipients, it is clear that current vaccine immunogens elicit antibodies that neutralize only a minority of circulating isolates. Thus, much progress needs to be made in this area. Also, though virus neutralization is considered a critical benchmark for a vaccine, this may not be the only benchmark for predicting success with antibody-based HIV-1 vaccine immunogens. The main targets for neutralizing antibodies to HIV-1 are the surface gp120 and trans-membrane gp41 envelope glycoproteins (Env) that mediate receptor and coreceptor binding and the subsequent membrane fusion events that allow the virus to gain entry into cells [3]. Antibodies neutralize the virus by binding these viral spikes and blocking virus entry into susceptible cells, such as CD4+ T cells [4,5]. In order to chronically replicate in the host, the virus exploits several mechanisms to shield itself against antibody recognition, including a dense outer coating of sugar molecules (N-linked glycans) and the strategic positioning of cysteine–cysteine loop structures on the gp120 molecule [6–8]. These shielding mechanisms, although highly effective, have vulnerabilities imposed by fitness constraints. Information on the precise location and molecular structure of these vulnerable regions could be valuable for the rational design of improved vaccine immunogens. Participants in the workshop identified four areas that, if given proper attention, could provide key information that would bring the field closer to an effective antibody-based HIV-1 vaccine: (1) structure-assisted immunogen design, (2) role of Fc receptors and complement, (3) assay standardization and validation, and (4) immunoregulation of B cell responses.

Alan Bernstein, executive director, Global HIV Vaccine Enterprise, Seattle, Washington

Physics student turned biomedical scientist becomes executive director of Global HIV Vaccine Enterprise

AIDS Vaccine Development: Challenges and Opportunities

A quarter of a century after AIDS became known as a frightening new disease, substantial progress has been attained on treatments that convert this once certain death sentence into a manageable chronic disease. While some prevention successes have been attained (e.g., screening of the blood supply in industrialized countries), a safe and effective vaccine—the “holy grail” of public health prevention—remains elusive. In the late 1990s, the first HIV vaccine taken to phase III trial, the VaxGen gp120 vaccine (VaxGen, Brisbane, CA, USA), became the basis for substantial debate and controversy between empiricists (generally public health persons who believed that the urgency of the pandemic required taking some risks, including a potentially low-efficacy vaccine as a first step) and reductionists (generally basic scientists and researchers who felt that the gp120 vaccine was unlikely to work given our state of knowledge and who wanted to wait for a better candidate vaccine). With trial results now available, we know that this vaccine was not efficacious. We also know that a phase III trial, although challenging to organize and conduct among persons at high risk, is doable. What else we do and do not know scientifically is summarized nicely in the 19 chapters of this excellently edited, concise (150 pages), softbound book. The book is organized into 5 parts: Global Overview; What Does a Vaccine Need to Do?; Preclinical Development: Design Challenges; Clinical Trials; and From Testing to Deployment. Each chapter, written by experts in each field, is impressive in its balance of compactness (3–4 double-sided pages, including references), technical content, and user-friendliness (abstract and conclusion for each chapter make quick review easy). The authors and editors are to be commended for bringing each of the key topics relevant to HIV vaccines to the reader in a highly accessible form. Key topics include HIV pathogenesis; the twists and turns of what specific knowledge of simian immunodeficiency virus and nonhuman primates is or is not applicable to HIV and humans; and the highly technical nature of modern immunology, virology, and structural biology. The editors were careful to include chapters on important nonscientific aspects of HIV vaccine development, such as clinical site development, regulatory issues, scale-up, and manufacturing. This book provides an excellent introductory overview for the beginning HIV vaccine researcher or any person who needs a more technical primer on the various aspects of the HIV vaccine challenge. The number of HIV vaccine researchers is now increasing, given the support of several organizations (e.g., Bill and Melinda Gates Foundation) and collaborations (e.g., Global HIV Vaccine Enterprise, the Partnership for AIDS Vaccine Evaluation, and the Center for HIV-AIDS Vaccine Immunology). These organizations, collaborations, and researchers are attempting to better organize the human and technical resources needed to challenge this formidable foe on the scale of the Manhattan Project or the March of Dimes search for a polio vaccine. Let us hope that they will eventually succeed.

AIDS vaccine development Challenges and opportunities

AIDS vaccine development Challenges and opportunities

The discovery value of “Big Science”

The increasing complexity of biomedical research is leading to the exploration of new models for large-scale collaborative research. This Big Science approach, however, has created anxieties and potential tensions between investigator-driven research, and research guided by a more organized, collaborative effort. Another potential tension exists between research conducted purely in search of new knowledge and research aimed at finding solutions. We argue that big biomedicine—the work of coordinated multidisciplinary groups that use the latest technologies to solve complex problems—can be an important way to harness the creativity of individual investigators, stimulate innovation, and supply the infrastructure, experimental systems, and resources needed to solve the urgent health problems confronted by our global society. We discuss this using the example of the Global HIV Vaccine Enterprise.