The Asia-Pacific region is the world's largest and most diverse in terms of geography, populations, cultures, and political and economic systems. Stretching halfway across the globe, from Iraq to Tahiti, it is home to the world's most populous countries--China, India, Indonesia--as well as some of the smallest and most isolated, the island states of the South Pacific.
In November 2001, clinical studies continued in Oxford, UK on an AIDS vaccine strategy that uses a naked HIV-DNA construct followed by a second MVA-based (modified vaccinia Ankara) vaccine. Participants in an earlier trial of the HIV-DNA vaccine (begun in August 2000) were invited to enroll in the new study, which will test the safety of MVA as a "boost" and begin examining whether the combination elicits better immune responses than either vaccine alone.
Thailand's launch of the VaxGen Phase III trial in March 1999 represented another "first" for a nation that has been one of the world's most pro-active in efforts to reduce the spread of HIV. But beyond its being the first AIDS vaccine efficacy study in a developing country, the ongoing trial is breaking ground on another front of the prevention battle: . . . .
As the three-year VaxGen trial in Bangkok approaches its midpoint, Thailand is already deep in the midst of preparations for a second Phase III AIDS vaccine study. Slated to begin in the latter half of 2002, the trial will test whether a "prime-boost" strategy combining two vaccines--the first containing HIV genes in a canarypox virus vector (Aventis Pasteur's vCP1521 construct), followed by VaxGen's envelope (gp120) protein subunit--can protect against heterosexual transmission.
With HIV vaccines based on canarypox poised to enter Phase III studies, and HVTN, a new prime-boost strategy using a related viral vector is just entering the clinical development pipeline. At the Bangkok and Melbourne meetings, researchers from an Australia-based consortium reported on their program to combine a DNA vaccine prime with a new HIV vaccine made from fowlpox, and possibly also with a cytokine (an immune-enhancing "messenger" molecule).
Dr. Supachai Rerks Ngarm is currently Senior Expert in Preventive Medicine in Thailand's Department of Communicable Diseases, Ministry of Public Health, and a principal investigator of the prime-boost Phase III vaccine trial due to start in 2002 . . . .
Yet twenty years into the epidemic, we must ask why we aren't farther along in this endeavor. Are the different worldwide efforts always well-focused on the challenge, which is to make available an effective, affordable HIV/AIDS vaccine?
Pediatrics and vaccinology have long gone hand-in-hand. Children, including young babies, were key participants in trials of polio, BCG and measles vaccines, all of which are now given to infants. But HIV has turned this paradigm on its head.
One of the field's major new meetings, "AIDS Vaccine 2001" was held in Philadelphia on 5-8 September 2001 and attracted a crowd of over 1,000 attendees. Co-sponsored by several US NIH entities together with UNAIDS, the US CDC and the French ANRS, the conference featured a packed program on topics ranging from vaccine design and basic virology to plans for clinical trials.
As Thailand prepares for Phase III testing of a prime-boost vaccine strategy in 2002, the US HIV Vaccine Trials Network (HVTN) is developing efficacy trial plans for a similar canarypox-gp120 combination starting in 2003.
This issue of the IAVI Report is devoted to women and gender-related issues in AIDS vaccine research. It's a focus that could raise eyebrows: What is there to talk about? After all, vaccine science has rarely paused to consider gender differences, and has rarely had to.
In 1997, the antenatal clinic at Mulago Hospital in Kampala was the site of a clinical trial that launched a thousand hopes for the battle against AIDS in children. HIVNET 012 showed that a simple, cheap regimen of the antiretroviral drug nevirapine (NVP)—one dose to the mother in labor, one to the infant within 72 hours of birth—reduced rates of HIV transmission at delivery by nearly 50%.
One of the biggest puzzles in understanding mother-to-child transmission of HIV is why the majority of babies born to HIV-infected women remain uninfected in utero, at birth and-perhaps most remarkably-during breastfeeding.
In Kenya the HIV prevalence in men and women is similar. But in young people between 15 and 24, there is a big gap—many more women are infected. In towns with high prevalence the risk to young women is 3 times higher than for young men. Since the epidemic in women starts earlier, they are dying very young.
In the US, long-term studies of HIV-infected and high-risk people have mainly involved gay men— the group most heavily impacted in the epidemic's early years. But a continent away, in the Pumwani district of Nairobi, group of just over 100 women have become well-known to HIV researchers around the world by offering tantalizing evidence that the immune system can, in rare cases, fight off HIV.
The Human Leukocyte Antigen (HLA) system is, in some respects, the immunological equivalent of a sophisticated alarm system. HLA molecules are produced within human cells, and act as receptacles for fragments of cellular or foreign (e.g., viral) proteins. The HLA molecules then display these fragments (known as peptides) on the outside of the cell; a single cell is typically adorned with several hundred thousand different HLA-peptide complexes.
The Nairobi ESN women are not the only group of exposed seronegative individuals being followed prospectively. Similar examples of possible HIV resistance have been reported from other cohorts, which typically fall into one of three categories: commercial sex workers (CSW) (who are usually exposed to many different HIV strainst), serodiscordant couples (wherein one partner is HIV-positive, the other, negative), and perinatally exposed infants (see article, "Closing in on Immune Protection in the Women of Pumwani").
After years without success in efforts to make a vaccine against herpes simplex virus type 2 (HSV-2), which causes chronic bouts of painful genital sores—and is present in over 20% of US adults—last year finally brought some progress. Results from two Phase III trials showed that a vaccine developed by SmithKline Beecham (now GlaxoSmithKline, or GSK) appears to offer some protection against disease.
A short distance—but a world away—from the bustle of Manhattan, the South Bronx is home to one of two "Project Achieve" HIV prevention research sites, this one focused on high-risk women. Run as a collaboration between the New York Blood Center's epidemiology lab and New York City's Department of Health, the site conducts vaccine and preparedness studies, along with trials of behavioral interventions and microbicides, in cohorts of mostly poor, minority women.
In many countries around the world, the rate of HIV infection in women is rising faster than in any another group. In sub-Saharan Africa, where over 70% of the world's HIV-positive people live, women made up about 55% of those living with the virus at the end of 1999, according to UNAIDS, and young women (ages 15-24) in the hardest-hit countries were up to three times more likely to be infected than males of the same age. In the US, women accounted for 23% of all new AIDS cases in 1999, compared to only 7% in 1986.
In the remote rural regions of South Africa, young women constitute the highest risk group for HIV infection, as they do throughout much of the continent. Over the past several years, one such location—a tribal ward called Hlabisa (pronounced "shla-bisa")—has launched intensive vaccine preparedness efforts, under the auspices of South Africa's Medical Research Council (MRC) and NIAID's HIV Vaccine Trials Network (HVTN).
Presidential AIDS Advisory Council Presses On, Renewing Call for Vaccine Support; Free Online Journal Access for Developing Countries; Allovaccination as an AIDS Vaccine Strategy
As delegates from around the world gather in New York for the United Nations Special Session on AIDS (UNGASS, 25-27 June 2001), efforts to establish a global fund to help bankroll international action against infectious diseases in developing countries are showing results..
The human body's mucosal surfaces—a vast immunological territory with a surface area equivalent to one and a half basketball courts—are its first immune barriers to the outside world. As such, they are thought to play a key role in susceptibility to HIV.
For the first time in the 20-year history of AIDS, the United Nations General Assembly has convened a special session dedicated exclusively to addressing the global epidemic. National delegates from the highest political levels, including at least a dozen heads of state, will gather in New York from 25-27 June 2001, in an attempt to intensify international action and mobilize resources to respond to the global crisis.
There is a Creole proverb that has long been a metaphor for Haiti's struggles: Deye mon, genyen mon—Beyond mountains, more mountains. From above, the island appears as a jagged range of overlapping barren crests completely denuded of trees—somber evidence of this once-lush Caribbean nation's steady decline into abject poverty.
Legislation aimed at stimulating more private sector research on vaccines against AIDS, malaria, and tuberculosis has been introduced in the US Congress for the third consecutive year. Although it was not incorporated into the tax bill signed by President George W. Bush in May, The Vaccines for the New Millennium Act of 2001 could still be considered later in this year's Congressional session.
Earlier this year, IAVI conducted a series of interviews with representatives of ten pharmaceutical and biotech companies and industry organizations. Participants were asked about the potential effectiveness of tax and other financial incentives to stimulate research, development, production, and delivery of HIV vaccines.
José Esparza is Coordinator of the WHO-UNAIDS HIV Vaccine Initiative (HVI) in Geneva. A Venezuelan-born physician and Ph.D. biologist, he spent over a decade doing basic research in human virology at the Venezuelan Institute of Scientific Research in Caracas before joining the World Health Organization (WHO) in Geneva in 1986.
In April, 1999, Gary Nabel became the first director of the new Vaccine Research Center (VRC) at the National Institutes of Health in Bethesda, Maryland. Prior to taking this position, he was director of the Center for Gene Therapy and a Howard Hughes Medical Institute investigator at the University of Michigan in Ann Arbor.
In our last issue, founding editor David Gold wrote to you that he has moved on to other work at IAVI and that I have succeeded him as editor of the IAVI Report.
For six intense days at this well-known Rocky Mountains conference venue, researchers at the "AIDS Vaccines in the New Millennium" meeting (28 March-2 April) heard a broad range of presentations on HIV vaccine studies.
On Monday 19 March 2001, the Indian Ministry of Health and Family Welfare announced the launch of a partnership with IAVI to develop AIDS vaccines suitable for India. The agreement, which also includes the Indian Council for Medical Research (ICMR), provides a framework for joint projects in vaccine design, buildup of capacity for clinical trials and transfer of appropriate vaccine manufacturing technology to India.
India’s foray into AIDS vaccine development comes amid growing evidence of HIV’s increasing foothold in the country and its frightening implications for this nation of one billion people—about one-sixth of the world’s population.
Over 3,000 people attended the 8th Conference on Retroviruses and Opportunistic Infections in Chicago (4-8 February 2001), the largest annual HIV science meeting. While virology and antiretroviral therapy generally dominated the agenda at past conferences, this year's event continued the recent trend towards a more prominent role for immunology and vaccines.
In a special lecture, Bruce Walker (Mass. General Hospital, Harvard University, Cambridge), a leader in studies of cellular immune responses during HIV infection, reviewed his lab's work on supervised treatment interruption (STI). Also called "strategic" or "structured" treatment interruption by some researchers, STI is a promising but still unproven new front in HIV therapy.
Jon Cohen is a science journalist who began following the AIDS vaccine field in 1989 while working as a general reporter. A year later he started contributing to Science magazine, and since then, in his continuing role there as Contributing Correspondent, has written dozens of articles on the progress and difficulties along the road to an AIDS vaccine.
We would like to update you about a number of new developments at the IAVI Report. Four and half years ago, IAVI published the first issue of the IAVI Report. Released at the 11th International Conference on AIDS in Vancouver, the publication set out to report on the emerging field of AIDS vaccine research throughout the world.
Over the past few years, the mounting evidence that protection against HIV will require cellular immune responses (as well as antibodies) has fueled the development of vaccine candidates aimed at stimulating this arm of the immune system.
Davos – In a challenge to the world to move faster in developing an AIDS vaccine, the Bill & Melinda Gates Foundation has announced an unprecedented US$ 100 million in support of IAVI's $550 million funding target, bringing the amount of secured commitments to $230 million – over 40% of the total. The pledge is intended to spur mobilization of additional global support towards reaching this funding goal.
Nairobi — On 25 January 2001 the Kenyan Government endorsed plans for a Phase I trial of an HIV-DNA vaccine based on subtype A, the predominant strain in East Africa.
Abuja — From 15-17 January 2001, over 100 scientists, policy makers and representatives from multilateral organizations gathered in Nigeria's capital city for a "Consensus Building Workshop Towards the Development of a Nigerian National HIV Vaccine Strategy."
Jaap Goudsmit has worked in the AIDS field since the epidemic's early days, when he and several colleagues began studying progression to full-blown AIDS in cohorts of gay men and intravenous drug users — now the longest-standing HIV cohorts in the world.
As a growing number of HIV vaccine candidates enter the development pipeline, more attention is going to the mammoth task of planning and preparing for the large clinical trials down the road — the Phase III efficacy studies that test whether an experimental vaccine actually protects people against AIDS.
A short drive from the modern metropolis of Johannesburg lies the sprawling, bustling, impoverished township of Soweto, best known to outsiders as the site of fervent anti-apartheid activism in the 1970s.
James Ludigo stands in front of a crowded room in a spare, concrete-walled church in a rural village in the Rakai district of southwestern Uganda. He wears a baseball cap and T-shirt from his employer, the Rakai Project.
It's easy to see why Carletonville has become an epicenter for South Africa's AIDS crisis. Every day, some 70,000 migrant miners work grueling shifts in the largest gold-mining complex in the world.
HIV vaccine advocates, like other interest groups, witnessed the US Presidential inauguration in January 2001 without a clear sense of where the new president may be headed. Following a truncated transition and a campaign in which AIDS issues did not figure prominently, observers were left to discern hints from the political tea leaves.
This information is designed to support, not replace, the relationship that exists between you and your doctor.