IAVI's Scientific Blueprint 2000 seeks head-to-head trials and compressed timelines;With "goal in sight," IAVI urges US$1.1 billion in new funding for focused R&D effort

DURBAN, South Africa - The first AIDS vaccine candidate designed specifically for Africa will enter human trials this summer. The International AIDS Vaccine Initiative (IAVI) announced today that the Medicines Control Agency (MCA) of the United Kingdom has approved Phase I testing of a DNA vaccine based on HIV subtype A, the most common strain in Kenya and in many other parts of Africa.
Recruitment for the trial, involving 18 volunteers, will begin in Oxford in August, and, pending local approvals, another trial is expected to follow in Nairobi three to six months later.
The news from the British regulatory agency coincided with the release of Scientific Blueprint 2000: Accelerating Global Efforts in AIDS Vaccine Development, a global strategic research and development agenda from IAVI. The new scientific blueprint concludes that developing an effective AIDS vaccine in the shortest possible time will require a widening of the vaccine pipeline, compressed timelines for clinical trials, greater focus on the needs of developing countries, and an infusion of US$900 million to $1.1 billion in new resources.
"The goal is in sight," said Wayne Koff, Ph.D., IAVI's vice president for research and development. "We are increasingly confident that a protective vaccine will be ready in five to 10 years. This is the time to move forward with an aggressive and focused research agenda."
The vaccine candidate approved for testing in Oxford is the product of a partnership between the research teams of Professor Andrew McMichael of Oxford University in the United Kingdom and Professor J.J. Bwayo of the University of Nairobi in Kenya. The Oxford/Nairobi Partnership is the first of four vaccine development partnerships funded by IAVI, a global scientific organization dedicated to accelerating the development of AIDS vaccines for use throughout the world.
"This is a small but important step on the road to a preventive AIDS vaccine," said Seth Berkley MD, IAVI's president. "Although more than 25 vaccine candidates have been tested in humans, this is the first one designed for Africa, and the first one to emerge from our new model of public-private partnership. With over 15,000 new HIV infections every day, we cannot overstate the urgency of our challenge. The Oxford/Nairobi vaccine candidate has moved forward in near-record time-less than 18 months from the laboratory to the clinic." Berkley also noted that the DNA vaccine is the first component of a novel prime-boost vaccination strategy that will also include an MVA vaccine.
Prof. McMichael, one of the world's leading researchers in cellular immunity, said: "We are excited to begin trials for this approach. Our research indicates that this vaccine has a very good chance of stimulating cellular immune responses to HIV. Research also suggests that white blood cells activated by the vaccine can destroy virus-infected cells. For HIV, this approach may be more effective than the traditional vaccine approach of stimulating antibodies."
The rationale for this approach comes from extensive studies of sex workers in Nairobi. Despite frequent exposure to HIV, a small minority of these women has resisted infection over many years. "We hope this vaccine will stimulate the same strong cellular immune response to HIV that we have seen in these women," said Prof. Bwayo, who is chairman of the Department of Medical Microbiology at the University of Nairobi.
Bwayo said, "Until now, most AIDS vaccines have been made from strains circulating in the North, specifically, subtype B. The development of this vaccine begins to address the great need for vaccines designed specifically for Africa." He added: "We recognize that vaccine trials on HIV/AIDS present unique challenges. Any vaccine trials on humans must go through rigorous safety and ethical protocols. With HIV we are insisting on even higher standards of safety and ethics. The proposed vaccine is not curative but preventive. It is inspired by findings by our scientists in Nairobi."

The Rt. Hon. Clare Short, UK Government Secretary of State for International Development, welcomed the news of the trial, saying, "The search for a vaccine represents the best hope to conquer AIDS in the world. The UK government was pleased to be the first government to offer major support for IAVI. We applaud IAVI's bold plan to accelerate AIDS vaccine development, and hope that this first IAVI-sponsored trial bears fruit."
Scientific Blueprint 2000 Lays Out Ambitious Plan
IAVI laid out its global strategic plan in a new scientific blueprint that calls for putting 25 innovative vaccine designs into development and conducting head-to-head trials among them, leading to six to eight efficacy trials by 2007. IAVI said the new plan could slash the time needed between a product's design and global licensure by as much as 50%.
The Scientific Blueprint 2000 also calls for a greater focus on vaccines applicable for use in developing countries. While the significance of variations in subtype is not fully understood, IAVI's scientific philosophy is to match a vaccine candidate to the population in which it is intended for testing. The new report updates and extends IAVI's landmark Scientific Blueprint for AIDS Vaccine Development, which was released at the 1998 World AIDS Conference in Geneva.
"Two years ago, we stood before the world and proposed a program to put the AIDS vaccine development effort back on track," said Berkley, IAVI's president. "The world responded with political leadership and resources. The amount spent globally on AIDS vaccines has more than doubled, and IAVI itself has raised more than US$100 million and launched the development of four innovative vaccine candidates for Africa. Others, including the U.S. National Institutes of Health and the European Union, have embraced our model of product development-focused applied research," Berkley added.
"However, these stepped up efforts have not kept pace with the global pandemic," Berkley continued. "AIDS has now surpassed tuberculosis and malaria as the leading killer among infectious diseases. Safe sex efforts have been extremely difficult to sustain on a population basis. A vaccine is the best hope for ending the epidemic."
"This new blueprint represents some of the world's best thinking on how to get the job done," Jaap Goudsmit, Ph.D., chair of IAVI's Scientific Advisory Committee. "Its focused, ambitious agenda is distilled from the findings from IAVI's scientific think tanks and other consultations with leading scientists around the world," added Goudsmit,
The new blueprint states that, while the vaccine development pipeline has widened since 1998, there is still no product in clinical trials for nearly half of the 11 different vaccine strategies the report identifies. Few of the vaccines in development are tailored for use in developing countries, where over 95% of new infections occur.
"Fifteen years since the identification of HIV as the cause of AIDS, only one vaccine strategy has progressed to Phase III efficacy trials," said Goudsmit.
The report proposes parallel, rather then sequential, Phase III efficacy trials in several countries or regions hardest hit by AIDS. This is not only to maximally accelerate the testing, but also to determine the breadth of protection by each vaccine design to avoid delays in licensing and implementing use of the vaccine across different regions and in different populations
The report also proposes moving multigenic approaches forward, as well as creating a consortium of scientists to identify and develop vaccines capable of inducing broadly effective neutralizing antibodies against HIV.
"Maximizing the number of innovative designs will maximize the chance of success," said Goudsmit. "Many interesting avenues have yet to be pursued," he added. "That the Oxford/ Nairobi Partnership is moving forward so quickly helps validate IAVI model of public-private partnership."
The new blueprint concludes that AIDS vaccine development remains woefully underfunded given a vaccine's potential to end the epidemic for all time. The report estimates that, of the US$20 billion the world spends annually on AIDS, only US$350 million is for vaccine research and development. "Closer examination reveals that less than one third of that amount is being spend on product development," according to the report, with an even smaller percentage focused on the needs of developing countries.
The new plan would cost between US$900 million and $1.1 billion above currently projected expenditures to implement. IAVI has raised over US$100 million since its inception in 1996. The new expenditures would be shouldered not only by IAVI but also by national and transnational research agencies and the pharmaceutical and biotech industries. However, to catalyze the scientific agenda, IAVI is planning to establish four to eight new vaccine development partnerships, in addition to the four that are already ongoing. "We hope that private industry, along with national and transnational research agencies, will pick up the challenge and fund the others," Berkley said.
The cornerstone of IAVI's scientific program is its vaccine development partnerships (VDPs). Designed to move promising experimental vaccines into clinical trials as rapidly as possible, VDPs link researchers from academia or biotechnology companies with vaccine manufacturers and with clinical researchers in developing countries. In addition to providing funds, IAVI also provides expertise, as needed, in areas ranging from project management to regulatory affairs and infrastructure for clinical trials.
In choosing which experimental vaccines to move forward, IAVI looks for novel approaches that have shown significant promise in non-human primates and can progress to clinical trials within two years or less. The candidate vaccine is then tailored to match the predominant HIV strain in the region where the cllinical trials will take place-a mechanism which ensures that vaccines are developed for the world's poorer nations and not just for the profitable markets in industrialized countries.
The International AIDS Vaccine Initiative is an international non-profit scientific organization founded in 1996 whose mission is to ensure the development of safe, effective, accessible, preventive HIV vaccines for use throughout the world.
IAVI's work focuses on four areas: accelerating scientific progress, mobilizing support through advocacy and education, encouraging industrial involvement in AIDS vaccine development, and assuring global access. IAVI is a collaborating center of UNAIDS. Its major donors include the governments, of the United Kingdom, the Netherlands and Canada, the World Bank, the Bill and Melinda Gates Foundation, the Rockefeller Foundation, the Sloan Foundation, and the Starr Foundation.
Earlier this week, IAVI released a blueprint aimed at making a vaccine available to all those who need it, entitled AIDS Vaccines for the World: Preparing Now to Assure Global Access.

For further information, visit www.iavi.org.
Contact: Victor Zonana (cellular: +44-77-147-98160) Kay Marshall (1-212-847-1044)


Fact Sheet on the Oxford-Nairobi Partnership


The Oxford/Nairobi Partnership is the first of four vaccine development partnerships funded by the International AIDS Vaccine Initiative (IAVI), a global scientific organization dedicated to accelerating the development of AIDS vaccines for the developing world. The partnership links the research teams of Professor Andrew McMichael of Oxford University in the United Kingdom and Professor J.J. Bwayo of the University of Nairobi in Kenya.

The vaccine is based on the work in the Medical Research Council Human Immunology Unit, headed by Professor McMichael and the extensive clinical studies on AIDS carried out in Nairobi in Prof. Bwayo's Department of Medical Microbiology. The two groups have been collaborating already for four years, preparing the way for vaccine studies in Kenya. The Oxford group has specialized in the nature of the immune response to HIV and has made key discoveries on how the immune system responds to viruses and how HIV can undermine these responses.

The required regulatory and ethical approval for the start of a Phase I trial with volunteers in Oxford has been obtained. Volunteers for this Phase I trial will be people at negligible risk of HIV infection. Recruitment of volunteers is expected to begin in early August and the trial will take from six to nine months to conduct.

The candidate DNA vaccine contains clade A HIV-1 gag gene and more than 40 epitopes, many of which are known to be immunodominant in HIV infected persons. The epitopes include clade A common in Kenya. Nearly all HIV-1 infected individuals make good CTL responses to this epitopes so these antigens in the candidate DNA vaccine should give it the potential to elicit a CTL response in the study participants. In addition, this vaccine candidate has the potential to induce of T helper responses may have indirect benefit by enhancing CTL responses.

Phase I trials are the first human tests of a candidate vaccine. They are generally conducted on small numbers of healthy adult volunteers who are not at risk for the disease in question. Clearly, the main goal of a Phase I study is the evaluation of the intrinisic safety of the candidate vaccine. The Oxford study will also provide an estimate of the immunogencity potential of the candidate vaccine as immunologic responses will be measured. Two doses of the candidate vaccine will be evaluated in this Phase I trial.

The DNA vaccine is the first part of a novel "prime-boost" vaccination strategy that will also include an MVA vaccine.