Science
12 December 2014 vol 346, issue 6215, pages 1261-1424
http://www.sciencemag.org/current.dtl

Perspective
HIV
Expanding the breadth of an HIV-1 vaccine
Gilad Ofek1, Ron Diskin2
Author Affiliations
1Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, MD, USA.
2Department of Structural Biology, Weizmann Institute of Science, Rehovot 76100, Israel.

One of the main problems encountered thus far in the quest for an effective HIV-1 vaccine has been that injected immunogens—virus-derived proteins against which an immune response is sought—generally only elicit antibodies with a narrow breadth of HIV-1 neutralization (1). During chronic infection, however, ∼10 to 30% of individuals naturally develop highly efficient antibodies that can neutralize multiple HIV-1 viral strains. These broadly neutralizing antibodies (bNAbs) have provided a template for the design of immunogens aimed at eliciting similar antibodies upon vaccination. On page 1380 of this issue, McGuire et al. (2) show that immunogens derived from the viral envelope glycoprotein of HIV-1 preferentially activate B cells that produce only narrow neutralizing antibodies (nNAbs). This supersedes the activation of B cells that produce the desired bNAbs, when both are present in the same pool of cells and are exposed to the same immunogen, possibly explaining the inability of previous vaccine candidates to achieve protective immune responses. By modifying the immunogen, McGuire et al. show that this preferential activation can be reversed in favor of the desired B cells, offering exciting new promise for vaccine design.