Hunting for that Ounce of Protection

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.

Haynes, who has been working on AIDS vaccine research since 1985, said even with the robust HIV prevention toolbox now available, a vaccine is still urgently needed. “We are treating the problem as a global emergency,” said Haynes, who has led the virtual consortium Center for HIV/AIDS Vaccine Immunology (CHAVI) for the last seven years and is now heading up one of two centers dubbed CHAVI-ID because they will focus on immunogen design (see IAVI Report blog, CHAVI: The Sequel).
 
Haynes talked about what researchers have learned from a continuing correlates analysis of samples collected from the RV144 efficacy trial in Thailand—the only trial thus far to show even a hint of vaccine-induced protection from HIV. The studies identified two different antibody responses—one which correlated with a greater risk of protection and the other with a greater risk of infection—and said this information is now helping shape new studies in both animals and humans to learn more about why the vaccine works and, more importantly, try and improve its efficacy.
 
But most of Hayne’s 30-minute plenary address (see also VAX June 2012 article, Q and A with Barton Haynes) focused on the work being done to better characterize the small but powerful subset of broadly neutralizing antibodies (bNAbs) that target HIV. These are uniquely valuable for two main reasons: they are so broad that they can blanket many of HIV’s many diverse strains and they are potent, so they might—in theory—provide protection even if induced at relatively low levels. 

The discovery of dozens of these bNAbs in individuals with chronic HIV infection in recent years has energized the field. But Haynes said these relatively rare molecules all have several unusual traits that have kept most of them out of the immunogen design game.  

He said they have unusually long complementary determining regions where they bind to HIV, which is not tolerated well by humans. They also are heavily mutated. But some might be amenable to immunogen design, and Haynes said researchers are now trying to figure out how to induce antibodies like them through novel vaccination strategies. 

For instance, researchers are looking at the lineage of B cells—which make antibodies—to try and develop ways of driving antibody maturation with fewer mutations, and then design immunogens that can engage the bNAbs at different stages of the development. “The unusual traits of [these] antibodies are necessitating completely new strategies that have never been used before [in vaccinology],” said Haynes. 

Francis Collins, who directs the US National Institutes of Health and chaired a session yesterday on the future of genomics and HIV, gave a talk on rapid advances in DNA sequencing—which in the last decade has become faster and cheaper—and other genetic tools that are helping researchers probe the bNAb response.  

He too noted that new studies are bringing us closer to a vaccine, though he said the twisted journey that the typical bNAb takes to maturity has made designing such a regimen difficult.