Given the scale of the AIDS epidemic and the limits of existing prevention technologies, demand for an AIDS vaccine can seem like a given. After all, who wouldn't want an AIDS vaccine? Similarly, with immediate scientific challenges to overcome, plans for manufacturing an AIDS vaccine may seem like a distant concern.
1994 was a watershed year for AIDS vaccine research. That year, without hard proof, envelope-based vaccines were determined inadequate to prevent HIV infection. The long-term fallout was substantial. Genentech left the business while Vaxgen picked it up. Chiron began a long re-tooling. Canarypox-based (ALVAC) vaccines became ascendant for clinical trials. IAVI came into being. NIH moved into financing product development.
Merck presented two sets of encouraging data from Phase I and II studies of a vaccine against human papilloma virus (HPV) at the HPV Clinical Workshop and 20th International Papillomavirus Conference (4-9 October, 2002).* HPV is the virus that causes genital warts and is linked to anal and cervical cancer-the leading cause of cancer deaths among women in the developing world. Merck's candidates, among the most advanced in the HPV vaccine pipeline, use HPV's L1 capsid protein.
While AIDS researchers often say that HIV is one of the most formidable pathogens ever targeted for a vaccine, the same holds true for the parasites that cause malaria--a disease that claimed 1 to 2 million lives every year, 75% of them children under five.
Since October 2001, Dr. Philip Russell has been a senior advisor in the US government's scaled-up program to stockpile vaccines against the most threatening bioterror agents, and to develop a new generation of safer, faster-working products. The program sits within a newly created Office of the Assistant Secretary for Public Health Emergency Preparedness in the Department of Health and Human Services (HHS).
This year saw the launch of three separate projects designed to ease comparison of results from vaccine trials by standardizing aspects of assays that measure cellular immune responses (Elispot and intracellular cytokine, or ICC) and neutralizing antibodies.
On 12-13 August, 2002, a Policymakers Conference on HIV/AIDS and AIDS Vaccine Initiatives was held in Kampala, Uganda. Attended by 180 Ugandan MPs, 3 Kenyan MPs, along with religious leaders, scientists and NGO representatives, the meeting was organized by a working group led by the Ugandan AIDS Commission (UAC) and funded by IAVI.
This time around, the world's largest AIDS conference had a very different tone than its predecessor. While Durban 2000 was a turning point in galvanizing global momentum for an all-out response to the epidemic, Barcelona was permeated with the hard reality that the world has not yet risen to that bold challenge, either in terms of political will or committed funding.
For the first time since the International AIDS Conferences began in 1983, this year's event featured an official satellite meeting on vaccines. "AIDS Vaccines for the World: Working Together to Accelerate Development and Delivery,"* attracted over 375 people from 61 countries and a wide range of sectors, reflecting the diversity of conference participants.
Barcelona introduced a new word--and a new worry--into the common AIDS parlance: superinfection. In one of the conference’s most widely-discussed presentations, Bruce Walker (Massachusetts General Hospital, Cambridge) described the case of an HIV-positive man who became infected with a second, closely related strain--despite having strong cellular immune responses that were controlling the first virus without drugs.
Is the AIDS vaccine glass half full or half empty? With a host of animal studies on candidates that fail to protect against infection but delay or prevent disease, it can be difficult to tell--especially since it’s not known whether results from animal studies are predictive of what will be seen in humans.
In the high--stakes world of AIDS research, two years can bring distinct shifts in priorities and paradigms. And every 24 months, the Olympic-sized International AIDS Conference provides an opportunity to assess and reflect on these changes.
AIDS vaccines and microbicides share many key goals. Both seek to develop prevention strategies that will stem the tide of new HIV infections around the world, and both share a keen awareness of women's vulnerability to HIV. But despite these similarities, the two fields have evolved separate strategies for mobilizing funds, political will and scientific support for their goals.
Here in the world's most populous democracy, rival political parties seldom show unity, whatever the cause. But a rare display of shared commitment recently took place at the International Policymakers Conference on HIV/AIDS (New Delhi, 11-12 May 2002),* where India's Prime Minister Atal Bihari Vajpayee and Opposition leader Sonia Gandhi each spoke about the epidemic and the extreme urgency of uniting the country in battling the disease and its devastating consequences. It is estimated that nearly 4 million people in India are living with HIV/AIDS.
The great burden of HIV/AIDS in Africa has led the international community to scale up the search for effective prevention strategies for this hardest-hit region. Appropriately, this has included a focus on developing new tools--especially vaccines and microbicides--that will reduce heterosexual transmission, which accounts for the vast majority of new infections on the continent. Many groups are now working to expand capacity for testing candidate HIV vaccines in Africa and to involve at-risk men and women in these clinical studies.
Alexandre do Valle Menezes and Ronaldo Mussauer de Lima
From 2-4 May 2002, a group of AIDS community advocates, government policymakers and others involved with HIV/AIDS met in the southern Brazilian town of Santa Cruz do Sul to begin forging plans for launch a vaccine trial site in their region. It was an unusual role reversal: in the normal course of events, such endeavors generally begin with researchers or funders, with communities coming on board later in the process after plans are underway.
When the Global Alliance for Vaccines and Immunizations (GAVI) was founded in 2000, it pioneered a new model for accelerating the delivery of public health commodities to developing countries. Specifically, the Alliance seeks to increase coverage of basic childhood immunizations in low-resource settings that have long lagged behind in being able to provide these vaccines, which include combinations like measles-mumps-rubella and diptheria-tetanus-pertussis (DTP), and hepatitis B.
US Congress Proposes Major Increase in Funds for Global AIDS, AAVP Launches Program at International Gathering, AIDS Vaccine Delivery Forum Held at African Economic Summit, AVAC Releases Report on State of AIDS Vaccine Development.
Unseasonably high temperatures and record-low amounts of snow set the backdrop for this year's Keystone Symposium on “HIV Protection and Control by Vaccination” in the Colorado Rockies. Inside, the thaw was more welcome, as early clinical trials data started to flow through the vaccine development pipeline. In the corridors, participants noted the welcome move towards convergence of virology and immunology, with virologists looking increasingly at approaches for immune control of HIV and immunologists envisioning therapeutic uses for vaccines alongside the goal of preventing disease and ultimately, infection.
On April 4, 2002, UK researchers immunized the first volunteer in a Phase IIa trial of an HIV-DNA vaccine and a second vaccine based on MVA (MVA.HIV) a weakened version of vaccinia virus. The study, headed by Jonathan Weber of London's Imperial College of Science, Technology and Medicine, is taking place there and at Oxford University, and will enroll 120 volunteers. It is sponsored by IAVI and the UK Medical Research Council.
On June 3-4, scientists, policy-makers, global health experts and other participants in the vaccine trials arena will gather in Cape Town, South Africa, for an international forum on the African AIDS Vaccine Programme (AAVP). The meeting will be an expanded debut for the AAVP, which has maintained a low profile since its inception in 2000.
It is 2007 and NewVaxCo, a hypothetical company, has just announced that its HIV vaccine proved highly effective in Phase III trials. The road to this great success has been bumpy: NewVaxCo spent grants and internal funds to develop the vaccine, and lost money along the way. In anticipation of public demand, it transferred intellectual property rights for the vaccine to four large developing countries--and is now worried about recouping its losses.
Michel Kazatchkine is director of France's Agence Nationale de Recherches sur le SIDA (ANRS) and head of Immunology at the Hôpital Européen Georges Pompidou in Paris. He is also President of the Technical Review Panel of the Global Fund against AIDS, Malaria and Tuberculosis and member of the WHO/UNAIDS AIDS Vaccine Advisory Committee, and advises EMEA, Europe's regulatory agency for medicines and vaccines.
Julie Milstien is Coordinator of the Access to Technologies Team, Department of Vaccines and Biologicals at the World Health Organization (WHO) in Geneva. The team's mission is to remove barriers to making vaccines and immunization-related technologies widely accessible. Before joining WHO in 1988, she spent 14 years at the US Food and Drug Administration.
On May 6, 2002, IAVI announced a new vaccine development partnership (VDP) with the Swedish biotechnology firm, Bioption AB, to develop HIV vaccines based on a new delivery system made at Stockholm's Karolinska Institute. The vaccines will use Semliki Forest Virus (SFV) replicons, which are genetically modified versions of SFV, a member of the alphavirus family.
The Board of Directors of the Global Fund to Fight AIDS, Tuberculosis and Malaria met in New York City for three marathon days (22-24 April) to make its first funding decisions and further define its mission. The Board approved US$ 378 million over two years to 40 programs in 31 countries. A second round of 18 proposals from 12 countries may receive $238 million, contingent on substantial changes and clarifications.
In a major decision for the AIDS vaccine field, the US National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), announced on 25 February that it will not proceed with a Phase III trial which was tentatively planned for early next year.
The US Army program on AIDS vaccines will be transferred from the Department of Defense (DOD) to the National Institutes of Health (NIH) on 1 October 2002. The move was ordered by the Bush administration's Office of Management and Budget in a directive issued on 4 January.
Last year, organizers of the annual Retrovirus conference--the largest US HIV research meeting--inaugurated a separate AIDS vaccine conference, leading many to expect that vaccines would not be featured at Retrovirus 2002. But the massive event, held 24-28 February in Seattle, found room for several vaccine talks, including the much-anticipated debut of data from human trials of Merck's new adenovirus-based vaccine candidate.
Malegapuru William Makgoba is president of South Africa's Medical Research Council (MRC) and is involved in AIDS vaccine development on a national, continental and global level. He began his scientific career as a child, tending his family's sheep and goats in Sekhukhueland, South Africa and paying close attention to the details of their life cycles, experiences he describes in his 1997 memoir "Mokoko."
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