Vaccine Briefs

Changes at The Global Fund and the NIH's Vaccine Research Center

The Global Fund to Fight AIDS, Tuberculosis and Malaria has picked Mark Dybul as its new executive director.

The appointment comes at a particularly rocky time for the Geneva-based organization, which has been grappling with both funding and management problems in recent years (see The Global Fund’s Uncertain Future, IAVI Report, Jan.-Feb. 2012). A medical doctor and immunologist who helped create and then led the President’s Emergency Program for AIDS Relief (PEPFAR) for three years, Dybul replaces Michel Kazatchkine, who left the organization in early 2012. Prior to Kazatchkine’s departure, The Global Fund’s board of directors appointed international banker Gabriel Jaramillo to the newly created position of general manager and put him in charge of day-to-day operations.

Dybul’s appointment also comes at an important juncture in the global campaign against HIV. According to the latest Joint United Nations Programme on HIV/AIDS (UNAIDS) report, released Nov. 21, there are now 25 countries reporting at least a 50% drop in new infections over the past year (www.unaids.org). But progress remains a bit spotty. The number of people newly infected in the Middle East and North Africa has, for example, increased by more than 35% since 2001, and incidence has dramatically climbed in Eastern Europe and Central Asia.

Dybul was a staff clinician at the US National Institute of Allergy and Infectious Diseases (NIAID) when he joined a task force that led to the creation of PEPFAR in 2003. The following year, he joined PEPFAR as deputy chief medical officer, and in 2006 was named U.S. Global AIDS Coordinator, overseeing PEPFAR. Since 2009, he has co-directed the Global Health Law Program at the O’Neill Institute for National and Global Health Law at Georgetown University.

Mark Harrington, executive director of Treatment Action Group, an AIDS research and policy group in New York, said in an email that he was happy about Dybul’s selection. “He is smart as a whip, his memory for data and science is outstanding, and he knows the players on the ground in many countries as a result of his years with PEPFAR.”

News of Dybul’s appointment was quickly followed by the announcement that the director of the Vaccine Research Center (VRC) at NIAID has joined Paris-based pharmaceutical giant Aventis as senior vice president and chief scientific officer. Gary Nabel, who joined the company on Dec. 3, will be based in Cambridge, Mass.

Nabel says the move was for personal reasons. His wife, Elizabeth, left her position as director of the US National Heart, Lung and Blood Institute in 2009, and is today president of Brigham and Women’s Hospital in Boston. “We’ve been commuting for three years and, quite honestly, if it hadn’t been for that, I wouldn’t have looked for a new job in the first place,” Nabel told Science writer Jon Cohen.

Nabel took the helm at the VRC when it was established 13 years ago, and NIAID’s Executive Director Anthony Fauci said he will be difficult to replace. “Dr. Nabel’s scientific contributions to ending some of the world’s worst infectious diseases and causes of human suffering are extraordinary,” said Fauci in a statement. “While I will continue to value his friendship, I will greatly miss his leadership and counsel here at NIAID.”

Among the noteworthy achievements of the VRC during Nabel’s tenure has been the identification in 2009 of several broadly neutralizing antibodies against HIV, including VRC01, which neutralizes 90% of a panel of Tier 2 viruses. The Center also conducted vaccine trials for Ebola, Marburg, West Nile, H5N1 avian influenza, and SARS viruses during his tenure. —Regina McEnery

Malaria vaccine candidate appears less effective in infants

New findings from an ongoing Phase III malaria vaccine trial in Africa suggest that the candidate, RTS,S, reduces the incidence of clinical malaria and severe malaria by a modest 31.3% and 36.6%, respectively, among children 6-12 weeks of age (N. Engl. J. Med. doi: 10/1056/NEJMoa1208394, 2012).

The efficacy of RTS,S in this group was less than that reported last year for older children enrolled in the same trial (N. Engl. J. Med. 365, 1863, 2011). In the older children, ages 5-17 months, the RTS,S vaccine candidate was found to reduce the incidence of clinical malaria and severe malaria by 55.8% and 47.3% respectively. And results of a randomized, open label Phase II trial published last year found that vaccine efficacy against clinical malaria was as high as 61.6% among infants (Lancet Infect. Dis. 11, 741, 2011).

Mary Hamel, a medical epidemiologist at the US Centers for Disease Control and Prevention and a principal investigator at one of the trial’s clinical research centers in Kisumu, Kenya, said researchers should gain some clarity when data from all the sites where the study was conducted are released in the next year or two. “We may find that by pooling the data across the 11 trial sites, differences in vaccine efficacy by malaria transmission intensity were masked,” Hamel says. “Most malaria cases in this analysis were from areas of very high transmission. Efficacy in areas of low or moderate malaria transmission may be higher, consistent with the Phase II trial.”

Still, the results from the Phase III trial of the RTS,S vaccine candidate are considered a major milestone, given the unusual challenges of designing a vaccine against the malaria parasite, which is spread from human to human through the bite of infected Anopheles mosquitoes. The parasites travel through the bloodstream to the liver, where they mature and release another parasitic form, the merozoites, which then enter the bloodstream and infect red blood cells. The parasites largely live inside cells, where they avoid the body’s immune responses, and humans do not develop sterilizing immunity against the pathogen. This means recurrent infections are common, at least in the developing world, where infected mosquitoes abound.

Developed and manufactured by GlaxoSmithKline (GSK) Biologicals, RTS,S contains a protein found on the surface of the P. falciparum sporozoite—the form of the parasite transmitted from mosquitoes to people—linked to hepatitis B vaccine antigen. It is formulated with AS01, an adjuvant manufactured by GSK.

The RTS,S candidate was co-administered with two licensed vaccines: a pentavalent vaccine against diphtheria, tetanus, pertussis, hepatitis B, and Hemophilus influenzae type B, and a polio vaccine. Scientists suggest that the co-administration of the licensed vaccines—including the Hep B antigen, which was effectively delivered twice—may have compromised the immune response to the RTS,S candidate. Hamel adds that infants have immature immune systems that respond less vigorously to vaccination, and that their responses might have been further compromised by antibodies against the sporozoites passed down by their mothers. Lower vaccine efficacy could also be associated with higher-transmission regions, but that will only be known when the site-specific analysis is completed.

The RTS,S candidate has been in development for nearly 30 years and would likely not have progressed this far were it not for the Malaria Vaccine Initiative (MVI), created by PATH, a Seattle-based non-profit established 30 years ago. PATH launched MVI in 1999, with an initial US$50 million grant from the Bill & Melinda Gates Foundation to accelerate the development of a malaria vaccine and ensure its accessibility in developing countries. MVI formed a product development partnership with GSK in 2001 to develop RTS,S. 

The fate of RTS,S remains unclear. MVI, which financed most of the research with a $200 million grant from the Bill & Melinda Gates Foundation, hasn’t yet announced any decision. “The efficacy came back lower than we had hoped, but developing a vaccine against a parasite is a very hard thing to do,” said Bill Gates in a statement on PATH’s website. “The trial is continuing, and we look forward to getting more data to help determine whether and how to deploy this vaccine.” —Regina McEnery