World AIDS Vaccine Day and HIV Discovery Commemorated
May 18 marked the 11th annual commemoration of World AIDS Vaccine Day, which is observed to honor the thousands of people working around the world to develop an AIDS vaccine. The significance of this day stems from a Morgan State University commencement address delivered in 1997 by then-US President Bill Clinton in which he called for renewed commitment toward the development of an AIDS vaccine. In the wake of some recent setbacks in the AIDS vaccine field, several organizations consider 2008 to be a particularly important year to raise awareness and support for continued efforts to develop an effective vaccine.
This year, organizations around the world coordinated educational campaigns and awareness activities to commemorate the day, including voluntary counseling and testing services for HIV. Several organizations in South Africa sought to heighten awareness about the importance of continuing AIDS vaccine research in light of last year’s failure of Merck’s leading AIDS vaccine candidate, which was also tested in South Africa in a Phase IIb test-of-concept trial, known as Phambili.
On May 20, leading HIV/AIDS researchers marked another important day—the 25th anniversary of the study published in the journal Science by Luc Montagnier and colleagues at the Institut Pasteur and La Pitié-Salpêtrière Hospital that described HIV as the causative agent of AIDS. A meeting was held at the Pasteur Institute in Paris in observance of this day at which leading scientists discussed ongoing HIV/AIDS research efforts, including sessions focused on the current strategies for AIDS vaccine development. Since the discovery of HIV, over 60 million individuals have been infected with the virus and more than 25 million have died. Alan Bernstein, the executive director of the Global HIV Vaccine Enterprise, wrote in an editorial published in the May 9 issue of Science, “The only end for a journey that began 25 years ago should be the development of a safe and effective HIV vaccine.”
In another commentary piece in Nature magazine, Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases (NIAID), reflected on the advancements made over the last quarter of a century in understanding and combating HIV/AIDS. He also called for a renewed commitment to overcoming the challenges in AIDS vaccine development and said, “It is now clear that we were naïve to think there would be a straight path from the discovery and characterization of HIV to the development of a vaccine.” On May 20, NIAID announced a new US$15.6 million, five-year program that will provide grants to 10 research teams to study the critical role of B cells in HIV infection with the aim of developing antibody-based AIDS vaccine approaches. Past NIAID grants focused primarily on T-cell based AIDS vaccine candidates, but following results from recent trials and the HIV Vaccine Summit held by Fauci in March, NIAID decided to place renewed emphasis on vaccine approaches that elicit neutralizing antibodies against HIV (see Balancing AIDS vaccine research, IAVI Report, March-April, 2008). —Alix Morris, contributing writer
Since the start of the epidemic, HIV has managed to outrun and outmaneuver scientists. It has done this in part by developing high levels of genetic diversity that have enabled the virus to rapidly spawn mutations capable of withstanding immune pressure. But the chase is on. Ultra-deep pyrosequencing technology, a fairly new high-throughput statistical method that produces DNA sequences in much greater numbers than previous techniques, is allowing scientists to inch closer to the most diverse region of the virus, the third hypervariable or V3 loop.
During April’s 15th Annual Workshop on HIV Dynamics and Evolution in Santa Fe, New Mexico, two separate papers—one now in publication—showed how ultra-deep sequencing can be used to produce huge amounts of genomic data about the viral population, including detailed identification of thousands of low-frequency viral variants. The ultra-deep sequencing helps identify, quantify, and track these minority virus populations as they evolve.
These hard-to-detect variants moving through the viral population are of great interest to AIDS vaccine researchers working to design effective immunogens that will induce the broadest immune responses against the greatest possible number of circulating HIV variants. Getting a clearer view of how HIV’s genetic material evolves over time could be the retroviral version of stealing the opponent’s playbook. And because the V3 amino acids are so diverse—as much as 35% can differ between strains within the same clade of HIV—this section of HIV’s envelope is integral in helping the virus evade the immune system.
Pyrosequencing allows researchers to sequence a single strand of DNA by assembling the complimentary strand alongside it, one base pair at a time. This permits researchers to detect which base was actually added at each step. It’s faster, cheaper, and less labor-intensive than the traditional Sanger method. The chief limitations with pyrosequencing are shorter reads—only about 250 nucleotides compared to 1,000 with the Sanger method—and data that is more error-prone.
The annual HIV Dynamics and Evolution Workshop, which attracts about 100 HIV scientists, began meeting to encourage dialogue among specialists who use a range of mathematical models and other computational tools to study viral and cellular dynamics, as well as viral evolution and population genetics. Other highlights from this year’s workshop included the description by University of Arizona researcher Mark Worobey of the oldest putative case of HIV disease identified to date from a lymph node sampled in early 1960 from a female patient in the former Central African country of Zaire, now the Democratic Republic of the Congo. The country has long been considered a hub for the dispersal and diversification of AIDS pandemic viruses, and the clade A-like strain detected in the woman showed the existence of distinct subtypes, evidence that its HIV group M ancestor dated back to at least the 1930s. The sample is also the only sequence-confirmed symptomatic group M HIV infection prior to the late 1970s, researchers said. —Regina McEnery