Research ArticleHIV

Polyfunctional Fc-Effector Profiles Mediated by IgG Subclass Selection Distinguish RV144 and VAX003 Vaccines

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Science Translational Medicine  19 Mar 2014:
Vol. 6, Issue 228, pp. 228ra38
DOI: 10.1126/scitranslmed.3007736

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More Is Better for Protection Against HIV

Recently, results from the first protective HIV phase 2B RV144 vaccine trial pointed to an unexpected signature of protection, not associated with the traditional mechanisms of vaccine-induced immunity, namely, neutralizing antibodies and killer T cell immunity. Instead, protection was associated with specific subpopulations of antibodies that were able to direct killing of HIV-infected cells. However, little is known about the properties of these killer antibodies or their biophysical features. In a new study, Chung et al. functionally profiled antibodies raised by the protective RV144 vaccine trial and its nonprotective predecessor, the VAX003 vaccine trial, both conducted in Thailand. RV144 vaccination uniquely induced antibodies capable of directing several different antiviral functions in a coordinated manner. In contrast, VAX003 vaccination predominantly induced single or uncoordinated antiviral responses. Functional coordination was regulated by the selection of antibody responses directed at vulnerable regions on the HIV envelope that were specifically tuned to enhanced functionality through the selection of a specific antibody subclass, IgG3, known to harbor strong antiviral activity. Collectively, these data suggest that vaccines able to induce broader antibody functional profiles, through the selection of more potent antibody subclasses, which target vulnerable regions of the virus, may represent a new means by which to achieve protection from HIV infection in the absence of neutralization.

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