In advance of today’s World AIDS Vaccine Day, a May 16 symposium sponsored by the New York Academy of Sciences (NYAS) provided an array of talks that largely focused on the progress and challenges in developing an AIDS vaccine. Michael Watson, who leads the global immunization policy group at Sanofi-Pasteur, noted during his opening that HIV scientists have made great strides in recent years, but that we “still don’t fully understand the enemy and how our bodies react to that enemy.”

Today I had a chance to talk to Mario Roederer, a T-cell immunologist at the Vaccine Research Center at the National Institute of Allergy and Infectious Diseases and a co-organizer of the “Protection from HIV” track at the Keystone meeting. He said the goal of the track was “to really expose the vaccine community to the microbicides people and vice versa because these approaches will have to be undertaken together in the future.” Roederer, who is married to microbicide researcher Laurel Lagenaur, said that as microbicides are becoming more specific, they are more similar to vaccines, which is why it is time that vaccinologists and microbicide researchers interact. 

In the last two years, several research groups have reported the isolation of a slew of new broadly neutralizing antibodies (bNAbs) that are more potent than the handful of such antibodies that had been known until then. Among them was VRC01, a bNAb isolated by researchers at the Vaccine Research Center (VRC) at the National Institute of Allergy and Infectious Diseases, which can neutralize over 90% of currently circulating HIV-1 strains (see Raft of Results Energizes Researchers, IAVI Report, Sep.-Oct. 2009). VRC01 and other HIV-specific bNAbs also have an unusually high degree of affinity maturation, which means that they are quite different from the germline version of the antibody that they are derived from (see Vaccines to Antibodies: Grow Up!, IAVI Report, July-Aug. 2010). 

Three years ago, the Center for HIV/AIDS Vaccine Immunology (CHAVI) began looking at a small cohort of hemophiliacs who had been exposed to HIV but remained uninfected despite receiving Factor VIII concentrates derived from large pools of blood plasma collected from donors, some of whom were infected with HIV (see Individual Armor Against HIV, IAVI Report, July-Aug. 2008).

Even when biomedical interventions against HIV work in clinical trials, as they have lately for several HIV prevention strategies, scientists don’t always know why. To borrow an analogy from the breathtaking backdrop of the annual Keystone conference this week, identifying the correlates of immune protection is a Nordic slog through the wilderness, not an Alpine run.

The antiretrovirals (ARVs) tenofovir and Truvada—a combination of tenofovir and emtricitabine—have received the lion’s share of attention lately for their role in preventing HIV infection, but researchers are experimenting with other ARVs that may also be effective topical pre-exposure prophylaxis (PrEP) agents.

At today's session on lentiviral diversity, Reuben Harris of the University of Minnesota gave an update on his studies of Apobec. In 2002, human Apobec3G was described as a host cell factor that inhibits HIV replication by introducing hypermutations, and HIV has evolved the Vif protein to inhibit Apobec3G by triggering its degradation. Apobec3G can therefore restrict replication of cells with HIV lacking Vif. By now, several additional Apobec3s have been described, but it has been unclear as to which ones contribute to HIV restriction. Harris presented evidence that four Apobec3s, Apobec3D, F, G and H all contribute to HIV restriction. “There is controversy surrounding every single Apobec except for Apobec3G,” Harris said. “So this work should, I hope, resolve that controversy. [We show that] those four are involved, the rest are not involved.”  

It’s probably a good sign when the keynote address on the opening night of a conference is interrupted by fireworks. That’s what happened to Ashley Haase of the University of Minnesota when he was close to the end of his address on HIV transmission on this opening night of the Keystone joint symposia on HIV Evolution, Genomics and Pathogenesis; and on Protection from HIV: Targeted Intervention Strategies, which is taking place from March 20-25 in Whistler, British Columbia. (The fireworks, I am told, take place every Sunday night as part of a “Fire & Ice Show” at the base of the Whistler Village Gondola.) 

Several speakers today discussed the development of new adjuvants, and Norman Baylor of the US Food and Drug Administration (FDA) gave an overview of the FDA’s safety and other regulatory requirements for adjuvants to be licensed for use in humans. “The biggest concern is safety,” he said. “That’s what we really need to demonstrate with these new adjuvants.” 

Today I had the chance to talk to Rino Rappuoli, one of the three scientific organizers of the Keystone Symposium on Immunological Mechanisms of Vaccination. Rappuoli, a vaccinologist, is the head of research at Novartis Vaccines and Diagnostics in Siena, Italy. Here is some of what he said. 

Systems biology was on the agenda today, and speakers described many projects that use this more holistic approach to study vaccination and infections. While there is a lot of promise in the approach, it also presents challenges. One challenge came up repeatedly today;  when researchers use microarrays to measure the expression of thousands of genes, the data of gene expression changes might just reflect changes in the abundance of certain cell types and not changes in gene expression in the same cell type. “This comes up again and again and again [that] you are getting these gene changes and much of what you are getting is simply the change in populations,” said Ron Germain of the National Institute of Allergy and Infectious Diseases, who mentioned the problem in his talk. 

Adjuvants were a much discussed topic on this second day of the conference, and it became clear that we are still far from understanding how they work. Take Alum, for example, which consists of insoluble aluminum salts. It is used in three quarters of all our childhood vaccines, according to Stephanie Eisenbarth of Yale University, one of the speakers today who studies Alum. 

"It does not rain in Seattle.” That’s what Shiu-Lok Hu of the Washington National Primate Research Center said just a few days ago in New Orleans when he announced that the next Annual Symposium on Nonhuman Primate Models for AIDS will be in Seattle next year. 

Genetics and genomics was the topic of most talks today, the last day of the conference. Jessica Satkoski Trask from the University of California, Davis said in her talk that when it comes to the availability of genetic tools, nonhuman primates (NHPs) have a long way to go compared with mice or fruit flies. “If you want a knock out mouse, you call the knock out mouse store and they send you the mice,” she said, referring to mice that have a gene knocked out. In contrast, “rhesus macaques and primates are not set up as a genetic model yet. There is going to be a need for a more and more diverse set of genetic tools.” 

Speakers today continued to discuss the development of nonhuman primate (NHP) models that can mimic different aspects of HIV infection and pathogenesis. Cristian Apetrei from the University of Pittsburgh described the development of an NHP model of elite controllers, HIV-infected individuals who control virus replication below detectable levels without treatment. Apetrei and colleagues infected rhesus macaques with simian immunodeficiency virus (SIV)agm, the SIV that naturally infects African green monkeys without causing disease. The rhesus macaques infected this way showed symptoms resembling human elite controllers. Apetrei said that having such a model is important because it makes it possible to study how elite control develops early after infection. 

“Food in New Orleans is more of a religion,” Andrew Lackner, director of the Tulane National Primate Research Center (TNPRC), said in the opening remarks at this year’s 28th Annual Symposium on Nonhuman Primate Models for AIDS, which is taking place from October 19-22 in New Orleans. It was therefore quite appropriate that the almost 200 conference participants were given a New Orleans cookbook, which features “fifty-seven classic Creole recipes that will enable everyone to enjoy the special cuisine of New Orleans.”