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144 Protection Against Heterologous SHIV Challenge Afforded by Immunization of Rhesus Macaques With a Subunit Immunogen that Mimics a Transition State HIV Envelope Structure

Fouts, T1; Lewis, G2; Pal, R3; Gallo, R2; DeVico, Anthony2

JAIDS Journal of Acquired Immune Deficiency Syndromes: April 2011 - Volume 56 - Issue - p 59
doi: 10.1097/01.qai.0000397330.72363.4a

1Profectus BioSciences, Baltimore, MD; 2Institute of Human Virology, Baltimore, MD; and 3Advanced BioSciences Laboratory, Rockville, MD

The coreceptor binding site of HIV-1 gp120 comprises some of the most conserved and functionally important residues on the viral envelope. Therefore, antibody responses to these epitopes should be highly cross-reactive and potentially useful for HIV vaccine development. To address this possibility, we have vaccinated rhesus macaques with various formulations of a subunit immunogen designed to raise humoral responses against conserved gp120 epitopes (rhesus full-length single-chain; rhFLSC). In heterologous high dose rectal challenge models, rhesus macaques were immunized with rhFLSC formulated in QS-21 or GPI-0100 adjuvants. Immunized animals challenged with heterologous SHIV162P3 exhibited vaccine dose-dependent nonsterilizing immunity; defined as accelerated clearance of plasma viremia and decreased tissue viral load compared with unvaccinated control animals. Such control correlated with stronger responses to a variety of conserved epitopes (including CD4-induced or CD4i) in rhFLSC-vaccinated animals. The control of infection was not associated with anti-CD4 responses or with neutralizing activity measured in conventional assays. In a different study, macaques were immunized with rhFLSC formulated in either Iscomatrix or RC-529 adjuvants and subjected to repeat dose challenges with SHIV162P3. Evidence of temporary sterilizing protection was seen in the RC-529/rhFLSC formulation, which was distinguished by high titer antibody responses to conserved CD4i epitopes in the absence of cellular responses. Protection was not associated with conventional neutralizing activity. Reminiscent of the RV144 clinical trial in humans, macaques that became infected upon challenge did not control viremia. Collectively, these data indicate that a single subunit vaccine has the capacity to prevent or control heterologous mucosal infection as a function of humoral immunity.

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