By Kristen Jill Kresge
Russia Announces Plan for Vaccine Research Center
In a final report on infectious diseases—one of the three key areas considered by the leaders of the G8 nations when they gathered in St. Petersburg, Russia from July 15-17—there was a pledge for continued support of HIV prevention, treatment, and care programs. The document highlighted in particular the development of AIDS vaccines and microbicides as priorities in the fight against the pandemic, as well as vaccines that could prevent other diseases that enhance an individual's risk of HIV infection. Other strategies promoted in the document included expanding the partnerships with developing countries to bolster capacity for research and development and ensuring that qualified healthcare workers are available in these regions.
In coordination with their hosting of this high-level meeting, Russia announced that it will request US$40 million to create a regional coordinating center for HIV/AIDS activities in Eastern Europe and Central Asia, with a portion of this funding being earmarked for the research and development of AIDS vaccine candidates. This proposal was introduced by the Russian Federation's chief doctor, Gennady Onishchenko, and was endorsed by heads of state who participated in the summit. The use of federal funding for this project is now under examination by officials in the Russian Ministry of Finance.
Although clear plans for this coordinating center are still vague, between five and seven existing Russian research centers will be involved in implementing the program. One of these institutes, The State Research Center of Virology and Biotechnology (Vector) in Novosibirsk, has already been involved in the development of two AIDS vaccine candidates. Other institutions that will play a role, including the Institute of Immunology in Moscow and St. Petersburg University, are also currently developing AIDS vaccine candidates. By the end of last year there were 350,000 documented HIV infections in Russia, compared to just 200,000 four years ago, and the epidemic continues to expand. In Russia, as well as in many other countries in Eastern Europe and Central Asia, there continues to be an exploding number of new HIV infections occurring mostly amongst injection drug users (seeInjection of hope). At sites in Estonia, Kazakhstan, Russia, and Belarus, HIV incidence rates among IDUs are reported at levels greater than 20%.
The first candidate developed by Russian scientists, known as Vichrepol, is now in clinical trials and information was presented in posters at both the International AIDS Conference in Toronto (see HIV prevention picks up momentum) and the AIDS Vaccine 06 conference in Amsterdam (see Ratcheting up T-cell responses). The candidate is a chimeric recombinant protein, rec(24-41), encoding the p24 full length viral protein and a gp41 fragment. This chimeric protein is conjugated with the adjuvant polyoxidonium, a synthetic polymer which is used in production of the influenza vaccine Grippol and was shown to enhance immune response in mice.
The ongoing clinical trial involves 15 volunteers who receive three intramuscular injections of Vichrepol at five different doses (2.5, 5, 10, 25, and 50 micrograms). The escalation of dose is only initiated once the safety and tolerability of the lower dose is established. So far two of the five doses have been evaluated and no side effects or safety issues have been reported. The poster presented at the AIDS Vaccine 06 conference reported that the vaccine candidate was found to induce antibody responses and suggested that subsequent studies will be needed to fully evaluate its safety and immunogenicity.
IAVI's AIDS Vaccine Blueprint Promotes Innovative Approaches to Evaluating Lead Candidates
The AIDS Vaccine Blueprint 2006: Actions to Strengthen Global Research and Development, IAVI's flagship publication, was released on August 15 during the International AIDS Conference in Toronto. This biennial publication outlines a series of new scientific and policy initiatives to accelerate the development of an AIDS vaccine through the involvement of industry, building research and clinical trials capacity in developing countries, and a new vaccine development model that will promote the rational design of vaccine candidates as well as an accelerated approach to clinical trials.
"The challenges to developing an AIDS vaccine are enormous," said Seth Berkley, Chief Executive Officer and President of IAVI. "We're trying to accelerate every component."
Industry's involvement in the development of an AIDS vaccine is seen by many in the field as an imperative, since much of the expertise in testing and manufacturing licensed vaccines is found within large pharmaceutical companies. Although some private sector entities are now actively engaged in AIDS vaccine research and development, the Blueprint calls for an increased level of commitment. "We've got to keep industry fully engaged," said Berkley.
Another area highlighted in the document is the continued need to enhance the ability of developing countries to conduct AIDS vaccine clinical trials. The Blueprint suggests the development of networks of excellence for both research and clinical trials in the countries hardest hit by the epidemic. "We need more clinical trial capacity and we also hope that more vaccine research will be done in developing countries," says Pontiano Kaleebu who works at the Uganda Virus Research Institute, a partner organization of IAVI. He also emphasizes the need for increased political support in these settings.
The Blueprint also recommends that the AIDS vaccine field implement an accelerated approach to clinical trials that will provide researchers with answers about a candidate's efficacy earlier in the development pipeline. This involves running several smaller Phase II trials in parallel with only those candidates that improve upon the best current products. These trials would be conducted in cohorts of individuals that are at high risk of HIV infection, allowing research to collect preliminary safety and efficacy data with a much smaller number of volunteers. Trials could therefore be run faster, providing answers in three to five years, and at a much lower cost. Berkley calls this strategy "a very bold design that requires a coordinated and prioritized effort."
New Funding for AIDS Vaccine Research Ushers in New Paradigm of Collaboration
On July 19 the Bill & Melinda Gates Foundation awarded US$287 million in grants that will be disbursed over the next 5 years to 16 different research teams, encompassing 165 investigators from 19 countries, to support innovative approaches to overcoming obstacles in AIDS vaccine research. This funding will support basic scientific research to design vaccines that can stimulate both humoral and cellular immunity. But beyond these challenges, several of the grants will also help research teams develop infrastructure both in developed and developing countries to allow for consistent evaluation of the immunogenicity and efficacy of vaccine candidates and will be used to oversee the establishment of vaccine production and delivery systems.
This series of vaccine grants are the Foundation's largest contribution to date for HIV/AIDS research and are in direct support of the scientific strategic plan established by the Global HIV Vaccine Enterprise, to which the Gates Foundation serves as the interim secretariat. This initiative brings together many of the leading teams that are currently working in the field and puts an even greater emphasis on collaboration and coordination of data between vaccine discovery teams at different institutions. Receipt of the grants is therefore contingent upon all groups agreeing to share data and intellectual property and working through a network of standardized laboratories to test their vaccine candidates. An editorial in the journal Nature Immunology referred to this new strategy as "a much-needed global experiment...that, if successful, could transform the process of vaccine design, development and delivery," (Nat. Immunol. 7, 9, 2006).
Five of the grants are to laboratories that focus on research into vaccine candidates that can elicit broadly-neutralizing antibodies against HIV. The largest of these grants, $25.3 million, was awarded to Robin Weiss of the University College London, UK. Among the other recipients was Barton Haynes of Duke University in the US, who leads a team of researchers who were recently awarded a $300 million grant from the US National Institute of Allergy and Infectious Diseases to form the Center for HIV/AIDS Vaccine Immunology (CHAVI), which was another funding stream resulting from the establishment of the Enterprise.
Another six grants were issued to laboratories or consortia working on vaccine candidates aimed at inducing cellular immune responses to the virus. IAVI was the recipient of a $23.7 million grant in this category. Other grantees include David Ho of the Aaron Diamond AIDS Research Center in New York City and Juliana McElrath of the Fred Hutchinson Cancer Research Center in Seattle.
The remaining five grants were provided to researchers who will form centralized facilities for vaccine candidate evaluation and will be involved in measuring the immune responses generated by candidates developed through the vaccine discovery programs, as well as handling the data collection.