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Boosting of ALVAC-SIV Vaccine-Primed Macaques with the CD4-SIVgp120 Fusion Protein Elicits Antibodies to V2 Associated with a Decreased Risk of SIVmac251 Acquisition.


ABSTRACT: The recombinant ALVAC vaccine coupled with the monomeric gp120/alum protein have decreased the risk of HIV and SIV acquisition. Ab responses to the V1/V2 regions have correlated with a decreased risk of virus acquisition in both humans and macaques. We hypothesized that the breadth and functional profile of Abs induced by an ALVAC/envelope protein regimen could be improved by substituting the monomeric gp120 boost, with the full-length single-chain (FLSC) protein. FLSC is a CD4-gp120 fusion immunogen that exposes cryptic gp120 epitopes to the immune system. We compared the immunogenicity and relative efficiency of an ALVAC-SIV vaccine boosted either with bivalent FLSC proteins or with monomeric gp120 in alum. FLSC was superior to monomeric gp120 in directing Abs to the C3 ?2 helix, the V5 loop, and the V3 region that contains the putative CCR5 binding site. In addition, FLSC boosting elicited significantly higher binding Abs to V2 and increased both the Ab-dependent cellular cytotoxicity activity and the breadth of neutralizing Abs. However, the FLSC vaccine regimen demonstrated only a trend in vaccine efficacy, whereas the monomeric gp120 regimen significantly decreased the risk of SIVmac251 acquisition. In both vaccine regimens, anti-V2 Abs correlated with a decreased risk of virus acquisition but differed with regard to systemic or mucosal origin. In the FLSC regimen, serum Abs to V2 correlated, whereas in the monomeric gp120 regimen, V2 Abs in rectal secretions, the site of viral challenge, were associated with efficacy.

SUBMITTER: Gordon SN 

PROVIDER: S-EPMC5026031 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Boosting of ALVAC-SIV Vaccine-Primed Macaques with the CD4-SIVgp120 Fusion Protein Elicits Antibodies to V2 Associated with a Decreased Risk of SIVmac251 Acquisition.

Gordon Shari N SN   Liyanage Namal P M NP   Doster Melvin N MN   Vaccari Monica M   Vargas-Inchaustegui Diego A DA   Pegu Poonam P   Schifanella Luca L   Shen Xiaoying X   Tomaras Georgia D GD   Rao Mangala M   Billings Erik A EA   Schwartz Jennifer J   Prado Ilia I   Bobb Kathryn K   Zhang Wenlei W   Montefiori David C DC   Foulds Kathryn E KE   Ferrari Guido G   Robert-Guroff Marjorie M   Roederer Mario M   Phan Tran B TB   Forthal Donald N DN   Stablein Donald M DM   Phogat Sanjay S   Venzon David J DJ   Fouts Timothy T   Franchini Genoveffa G  

Journal of immunology (Baltimore, Md. : 1950) 20160902 7


The recombinant ALVAC vaccine coupled with the monomeric gp120/alum protein have decreased the risk of HIV and SIV acquisition. Ab responses to the V1/V2 regions have correlated with a decreased risk of virus acquisition in both humans and macaques. We hypothesized that the breadth and functional profile of Abs induced by an ALVAC/envelope protein regimen could be improved by substituting the monomeric gp120 boost, with the full-length single-chain (FLSC) protein. FLSC is a CD4-gp120 fusion immu  ...[more]

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