By Regina McEnery
AVAC Reports on HIV Prevention Puzzle
In its 13th annual report, “Piecing Together the HIV Prevention Puzzle,” the AIDS Vaccine Advocacy Coalition (AVAC) said there is an “energized focus on discovery, innovation and basic science” in the field of AIDS vaccines, but noted that successful HIV prevention will likely depend on a combination of approaches and strategies. AVAC, which was formed in 1995, uses public education and policy analysis to advocate for the development of an AIDS vaccine. The organization has also taken a central role in advocating for other HIV prevention strategies, primarily pre-exposure prophylaxis (PrEP)—the delivery of antiretrovirals to uninfected individuals to prevent HIV infection. The report, written by AVAC staff, urged the HIV prevention field to prepare for the potential efficacy of prevention strategies such as PrEP, and called for governments in the countries hardest hit by HIV to “add specificity” around health-care infrastructure, as well as financial and human rights implications regarding the use of this modality.
“To maintain the ground gained, the rate of new infections must be slowed down,” said AVAC Executive Director Mitchell Warren in the report, which was released on May 18th, coinciding with World AIDS Vaccine Day (seeWorld AIDS Vaccine Day Observed).
Casting comprehensive HIV prevention as a puzzle still missing vital pieces—most notably a safe and effective vaccine against the virus—AVAC listed eight recommendations in its report. These recommendations include development of better communication tools to explain upcoming vaccine trials to a lay audience, as well as to communicate the results of the soon-to-be-completed Phase III prime-boost vaccine trial in Thailand. Another focus of the report is on the role of the Global HIV Vaccine Enterprise, an international alliance of researchers, funders, and advocates committed to accelerating the development of an AIDS vaccine. Based on interviews with various stakeholders, AVAC concluded that the “added value” of the Enterprise is “not yet completely convincing.” The AVAC Report recommended that the Enterprise should demonstrate greater leadership, particularly through publication of an updated scientific plan in 2010.
AVAC also highlighted advances in the field—more initiatives aimed at bringing young investigators into HIV prevention research was a notable area of progress. And with the initial results from the now infamous STEP trial nearly two years old, AVAC noted that the failure of Merck’s vaccine candidate has helped propel new and exciting directions in research. With a global recession threatening to strain budgets for HIV prevention, Warren says “funding decisions must be wise, non-duplicative and evidence-based, yet bold, expansive and innovative.”
New iavireport.org Launches
IAVI Report recently launched an updated and improved website, www.iavireport.org, which offers several new features, in addition to the content from all print editions of IAVI Report and VAX. Some of the new features include an Events and Meetings page with details on relevant scientific conferences and a searchable database of all preventive AIDS vaccine trials that allows users to access information by trial status or strategy. Soon, users will also be able to navigate the clinical trials database through an interactive map that displays all countries with ongoing AIDS vaccine trials.
The new site also features the first IAVI Report podcast series, called “A Living History of AIDS Vaccine Research,” which offers historical analysis from some of the leading voices in the field. The series opens with Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases. Additional installments in this series will be added to the site throughout the year, as well as other video projects.
Thoughts about the new site? The IAVI Report team would greatly appreciate any feedback or comments, which can be submitted through the Letters to the Editor or Contact Us links. If you do not currently receive IAVI Report orVAX, please click the Subscribe link to sign up for a free subscription.
Vaccine Considerations for H1N1
With H1N1 now evident in at least 73 countries, the World Health Organization declared the flu outbreak a pandemic—which it defines as a sustained community-level outbreak of a new virus in two or more regions of the world—the first in 41 years. At a May 28 conference, “Human Swine Flu (H1N1) and Novel Influenza Pandemics,” influenza scientists from public health agencies, academia, and the pharmaceutical sector gathered to discuss strategies for combatting H1N1. The conference, sponsored by The New York Academy of Sciences (NYAS), was billed as the first scientific conference devoted to the newly emergent strain.
Overall, public health agencies have become better able to recognize and respond to influenza outbreaks, but surveillance in the southern hemisphere—notably in South America and Africa—is hampered by poor infrastructure and lack of skilled personnel. “You can’t run a lab if you can’t get clean water and electricity,” said Michael Shaw, associate director for laboratory science in the Influenza Division at the US Centers for Disease Control and Prevention (CDC).
John Treanor, an infectious disease professor at the University of Rochester School of Medicine and Dentistry and a long-time influenza researcher, said at the conference that it is technically possible to incorporate the H1 component found in the H1N1 strain into the annually produced seasonal flu vaccines. But to do so would slow down production of the seasonal flu vaccine—which is usually available by mid-summer and administered in the fall—because the formula would have to be changed.
H1N1 Virus. Image courtesy of CDC / C.S. Goldsmith and A. Balish
The CDC has already shared seed virus with industrial vaccine manufacturers (Sanofi Pasteur and GlaxoSmithKline have acknowledged their work in this area) to begin development of a vaccine specifically against the H1N1 flu virus, and they hope to begin clinical trials this summer, said Shaw. Researchers will need to determine the optimal antigen to use in the vaccine and the required dose. Safety of the new construct must also be evaluated. The US National Institutes of Health (NIH) will be working closely with vaccine developers in testing the candidate vaccines for safety and immunogenicity, although the size and scope of the studies is still unclear at this point, said Dr. Anthony Fauci, director of the NIH’s National Institute of Allergy and Infectious Diseases. “We will go as quickly as we possibly can,” said Fauci, who was not at the May 28 conference.
Because production of the vaccine may be slow, at least in the beginning, countries, including the US, are considering using adjuvants to stretch the vaccine supply in the event that mass vaccination against H1N1 is recommended. One adjuvant, alum, which contains aluminum hydroxide compounds, is licensed in the US but hasn’t been found to work with influenza. Philip Dormitzer, senior director of viral vaccine research at Novartis Vaccines and Diagnostics, said Europe has been using a seasonal flu vaccine boosted with his company’s MF59 adjuvant—an oil in water emulsion—with good results.
Additionally, Dormitzer says some vaccine candidates against H5N1—a highly pathogenic strain of avian influenza that kills about half the people it infects—also utilizes adjuvants. “The utility of adjuvant vaccines is that you can make more doses,” said Dormitzer.
But even before considering adjuvants, public health officials must decide whether to vaccinate at all. Some influenza researchers warn that vaccinating prematurely can cause unnecessary complications like those that occurred three decades ago in the US.
In the winter of 1976, two epidemics of influenza—one an unknown strain thought to be similar to the swine flu that sparked the catastrophic 1918 Spanish flu—struck Fort Dix, a military installation in New Jersey. A few hundred soldiers became infected and one soldier died. The US government launched a massive vaccination campaign the following fall. More than 40 million Americans received the shots. Fears of a pandemic proved unfounded, but more than 500 people who received the swine flu vaccine developed Guillain-Barre syndrome, a rare neurological condition that causes paralysis and is sometimes fatal. The syndrome has been known to occur sometimes following vaccination.
Edwin Kilbourne, a professor emeritus at New York Medical College who helped develop the 1976 swine flu vaccine, said the decision to mass vaccinate was a tough one at the time, considering what else was unfolding. Along with the swine flu scare, US government officials were also soon dealing with what came to be known as Legionnaire’s disease.
Kilbourne noted that the current wave of H1N1 cases may seem relatively mild—most infected individuals have recovered spontaneously or with treatment—but he warned that the same was true for the first wave of the 1918 pandemic. It was the second, deadly wave several months later that triggered most of the illness and deaths.
New South Africa Institute to Tackle HIV and TB
The University of KwaZulu-Natal (UKZN) in South Africa, which claims the highest AIDS prevalence in the world, has teamed up with the Howard Hughes Medical Institute (HHMI) in Maryland to develop a research center focused on the twin scourges of tuberculosis (TB) and HIV. The toll from HIV and TB is huge. In 2007, there were 2.7 million new HIV infections and two million deaths attributed to the virus, according to the Joint United Nations Programme on HIV/AIDS (UNAIDS). Based on the latest figures from The Global Fund to Fight AIDS, Tuberculosis and Malaria, about two billion people—a third of the global population—were estimated to be infected with TB last year, while 9.3 million people became sick with active TB. When HIV and TB infections coexist, it intensifies the effect of both, often with dire consequences—TB is the leading killer of people with HIV/AIDS, according to UNAIDS.
The KwaZulu-Natal Research Institute for Tuberculosis and HIV (K-RITH) will receive US$60 million over 10 years from HHMI and will be housed within the Nelson Mandela School of Medicine in Durban. HHMI has committed about $20 million to construct K-RITH and $4 million a year for 10 years to support research. The UKZN is committing about $11 million for infrastructure costs. The new institute will be adjoined to the Doris Duke Medical Research Institute, which houses several AIDS research groups, including the Human Pathogenesis Programme headed by Bruce Walker, an HHMI investigator and head of the Ragon Institute in Boston, and the Centre for the AIDS Programme of Research in South Africa, led by Salim Abdool Karim.
K-RITH will initially focus on four research areas: the development of rapid and more effective diagnostic tests for TB; characterizing the genotypic and phenotypic properties of drug-resistant strains of TB; analyzing and characterizing complex immune responses to TB, particularly those seen in people also infected with HIV; and the study of recurrent TB infections in HIV-infected individuals.
K-RITH will also be used as a platform to test candidate vaccines, both for TB and HIV. “The institute is working on understanding spontaneous control of HIV replication and is focused on T-cell based vaccines, but the point is that the infrastructure will be there to facilitate the most promising new vaccine ideas forward,” says Walker, who was instrumental in establishing K-RITH.
Along with conducting research, K-RITH is also hoping to become a magnet for young African scientists who want to base their laboratory work in Africa but are hindered by the lack of research facilities and funding.
World AIDS Vaccine Day Observed
Twelve years ago on May 18, during a commencement address at Morgan State University, then-US President Bill Clinton called for a renewed commitment to the development of an AIDS vaccine. Several organizations and communities marked the 12th anniversary of Clinton’s speech—celebrated each year as World AIDS Vaccine Day—with candlelight vigils, charity walks, and educational fora to recognize recent developments in the field and to educate the world about the importance of AIDS vaccine research.
IAVI marked the day by focusing on recent accomplishments in the quest for a vaccine. In the past year, IAVI opened the world’s first laboratory devoted exclusively to AIDS vaccine research, known as the AIDS Vaccine Design and Development Laboratory, and partnered with The Scripps Research Institute to establish the HIV Neutralizing Antibody Center, dedicated to developing AIDS vaccine candidates that can elicit broadly neutralizing antibodies. In advance of World AIDS Vaccine Day, IAVI, the Global Health Council, and the Joint United Nations Programme on HIV/AIDS (UNAIDS) co-sponsored a Congressional briefing to spotlight advances in AIDS research in Africa.
In South Africa, the Emavundleni Community Outreach team, in partnership with the community advisory board and an adolescent outreach group called Future Fighters, sponsored an event at which volunteers distributed condoms along with information about AIDS vaccine research.
Other events included an informational forum in Jamaica focused on both circumcision and HIV vaccine research, and a program at a Baptist church in Georgia, “Hope in Our Souls,” to dispel common myths and increase AIDS awareness within the black community. The US Military HIV Research Program in Kenya sponsored research talks for students throughout the month. And the Treatment Action Group in New York City, along with the AIDS Vaccine Advocacy Coalition and the Global HIV Vaccine Enterprise, convened a discussion on the future of AIDS research.