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Antibody Frenzy

It wasn’t that long ago that the humoral immunity sessions at the annual AIDS Vaccine conference were more sparsely attended than the sessions focused on T cells. But at this year’s conference, antibodies seem to be the draw. The speculation by many researchers that the results of the RV144 trial in Thailand—the first to show vaccine-induced protection against HIV infection—were likely antibody related, along with the isolation of several new, and in some cases more potent, broadly neutralizing antibodies (more of which are expected to be described here this week) has catapulted these proteins back to prominence.

 

John Mascola of the Vaccine Research Center (VRC) at the US National Institute of Allergy and Infectious Diseases opened today’s plenary session with an update on some of the progress made recently in isolating several cross-reactive neutralizing antibodies that develop during the natural course of HIV infection. It is encouraging that the immune systems of HIV-infected individuals can make such antibodies, but there is still a long journey until this information can be used to design vaccine candidates. “This is a proof of concept,” said Mascola, “but the question is how does it help us? What insights do these antibodies provide for vaccine development?” He and others are now trying to answer these questions.

For the first time, Mascola reported on a broadly neutralizing antibody recently isolated at the VRC from samples collected from IAVI’s protocol G, a cohort of chronically HIV-infected individuals in Africa that also served as the source of the broadly neutralizing antibodies PG9 and PG16. This latest antibody, dubbed VRCPG04, was isolated using the same methods for plucking out antibodies that specifically target the CD4 binding site on gp120 that led to the discovery of VRC 01, 02, and 03, which were recently described (Science329, 811, 2010).

VRCPG04 can neutralize a high percentage of HV isolates and, like the other recently isolated broadly neutralizing antibodies, exhibits a high degree of affinity maturation, Mascola said. He and colleagues are now using genomic sequencing techniques to understand the genetic precursors of antibodies like VRC01 and how these germline antibodies evolve to attain the level of affinity maturation that allows them to neutralize HIV so well. Mascola said this work “may provide insights on how to design immunogens and which strategies to use for vaccination.” When that happens, the humoral immunity sessions will certainly be packed with people.