It almost felt like the summer drought had sapped the vaccine agenda at the 19th International AIDS Conference, so hard was it to find sessions devoted to the subject. But sparse as the selection was, Duke University scientist Barton Haynes offered a bit of an oasis with his overview today of the status of vaccine research and, particularly, two promising paths forward for the field.
Cure research hasn’t exactly been a hot topic at previous iterations of the International AIDS Conference (IAC). Things are different this time.
Funds for HIV prevention research and development remained essentially flat in 2011, dropping just 2%, or US$30 million, to $1.2 billion for the year, according to the HIV Vaccine and Microbicide Resource Tracking Working Group. As the Working Group noted, however, investments could have been much worse given the persistence of the global economic downturn.
When she walked on stage to deliver her plenary address at the International AIDS Conference being held here in Washington, D.C., US Secretary of State Hillary Clinton, whose call for an AIDS-free generation last year has become a rallying cry for the global AIDS community, was greeted with a standing ovation—but some catcalls and protests as well.
One of the most powerful and poignant symbols of the 30-year AIDS epidemic, particularly in the US, is the AIDS quilt—now 44,000 panels strong—yet until this weekend Michel Sidibe, the dynamic director of the Joint United Nations Programme on HIV/AIDS (UNAIDS) had never had the opportunity to view it.
A $31 million award from NIAID will start two new centers
The US National Institute for AIDS and Infectious Diseases (NIAID) has awarded an initial US$31 million to Duke University and The Scripps Research Institute (TSRI) to head up the Centers for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID). The centers are designed to build on the work of CHAVI, a virtual center created in 2005 to address some of the basic scientific problems impeding HIV vaccine design. CHAVI is now in the last months of its funding cycle.
Designing vaccine candidates to elicit broadly neutralizing antibodies (bNAbs) has proved a major challenge.
A minority of HIV-infected people generate such antibodies, but the average time for developing such responses is about 2½ years and only a small fraction of bNAbs protect against a broad range of HIV’s many different subtypes. The long—some say tortuous—development of bNAb responses entails a sort of continuous massaging of the immune system by the infecting virus.
Check out my article on the 15th Annual Conference on Vaccine Research, which showcased work being done combating HIV, malaria, influenza, rotavirus and other major global disease threats. The conference is sponsored by the National Foundation for Infectious Diseases in Maryland. The article can be found atwww.iavireport.org in our Special Features section.
John Mellors is the chief of infectious diseases at the University of Pittsburgh. His research focuses on antiretrovirals (ARVs), such as HIV resistance to them, using them for preexposure prophylaxis (PrEP) to prevent HIV infection in individuals, or modeling to see how PrEP affects the HIV epidemic. He also studies HIV reservoirs in patients on antiretroviral therapy (ART) and how to eliminate them. Mellors is also a member of the scientific advisory board of Gilead Sciences, the maker of Truvada, a combination of the ARVs tenofovir and emtricitabine. On May 10, Mellors spoke on behalf of Gilead at a hearing, where an expert advisory panel recommended to the FDA to approve Truvada for PrEP. The FDA is expected to make a decision in September. If approved, this would make Truvada the first ARV to be approved for PrEP. At the recent Cold Spring Harbor meeting on retroviruses, Mellors gave a Keynote address on how to eradicate HIV from the individual and from the world, focusing on cure research and antiretroviral drugs. I had the chance to talk to him about recent progress in cure research, and about what FDA approval of Truvada for PrEP would mean.
A prime-boost vaccination regimen using just Envelope—the protein from which the spikes on the outer surface of the virus are made—suffices to protect rhesus macaques from infection by simian immunodeficiency virus (SIV), but does not affect viral load in monkeys that do become infected, according to a recent study (Journal of Virology 2012, doi: 10.1128/JVI.00599-12). In the study, researchers used a so-called heterologous challenge, which is considered more realistic because the challenge virus differs from the type of virus carried in the vaccine.
One thing that seems pretty clear at this meeting is that the study of host cell restriction factors that inhibit viral replication or infection (such as Trim5α and tetherin) has been literally exploding in the past ten years. “There has been a remarkable gold rush in interest in restriction factors,” said Jonathan Stoye, a virologist from the MRC National Institute for Medical Research in London, in his Keynote address on Wednesday. He said that in 2000, the Cold Spring Harbor Retrovirology meeting featured just two talks on such factors, whereas this year, more than a quarter of the talks were about restriction factors.
Monday night, the 37th annual meeting on retroviruses at Cold Spring Harbor Laboratory started with its first session. The meeting, which takes place here from May 21-26, covers all aspects of retrovirology, although most presentations are on HIV. With 120 talks and almost 200 posters in five days, the meeting is “an intense experience,” said Vineet KewalRamani of the National Cancer Institute in Frederick, Maryland, one of the co-organizers this year.
One of the intriguing questions raised by the RV144 AIDS vaccine trial in Thailand, which demonstrated historic though modest (31.2%) vaccine-induced protection from HIV, was whether the protective effect of the vaccine candidates waned over time. Data showed that vaccine efficacy was nearly 60% during the first year following vaccination, but because the trial was not designed to look at whether a certain number of injections were effective or if the protective responses waned with time, investigators were unable to draw any conclusions about this observation (see Raft of Results Energizes Researchers, IAVI Report, Sep.-Oct. 2009).
In his talk at the 15th Annual Conference on Vaccine Research about advances in vaccine discovery, David Weiner, chair of the gene therapy and vaccines program at the University of Pennsylvania, recalled that it has been about two decades since the “public coming out” of DNA-based vaccination in AIDS research.
The last two days of the conference saw promising news for eradication research. Yesterday, Sarah Palmer from the Karolinska Institute in Sweden reported that she and her colleagues compared single HIV RNA sequences from plasma taken from eight patients just days before they started HAART, with sequences of single integrated proviral HIV DNAs in T cells from the same patients’ blood and gut associated lymphoid tissue (GALT) taken between four and ten years later.
The HIV reservoir in latently HIV infected cells is considered one of the major remaining obstacles for eradication of HIV. Researchers hope to treat HIV infected patients who are receiving antiretroviral therapy (ART) with drugs that induce HIV expression in latently infected cells so that they can then try to remove or kill those cells.