Kinetic rates of antibody binding correlate with neutralization sensitivity of variant simian immunodeficiency virus strains

被引:44
作者
Steckbeck, JD
Orlov, I
Chow, A
Grieser, H
Miller, K
Bruno, J
Robinson, JE
Montelaro, RC
Cole, KS
机构
[1] Univ Pittsburgh, Sch Med, Dept Med, Div Infect Dis, Pittsburgh, PA 15261 USA
[2] Univ Pittsburgh, Sch Med, Dept Mol Genet & Biochem, Pittsburgh, PA 15261 USA
[3] Tulane Univ, Med Ctr, Dept Pediat, New Orleans, LA 70112 USA
关键词
D O I
10.1128/JVI.79.19.12311-12320.2005
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Increasing evidence suggests that an effective AIDS vaccine will need to elicit both broadly reactive Immoral and cellular immune responses. Potent and cross-reactive neutralization of simian immunodeficiency virus (SIV) and human immunodeficiency virus type 1 (HIV-1) by polyclonal and monoclonal antibodies is well documented. However, the mechanisms of antibody-mediated neutralization have not been defined. The current study was designed to determine whether the specificity and quantitative properties of antibody binding to SIV envelope proteins correlate with neutralization. Using a panel of rhesus monoclonal antibodies previously characterized for their ability to bind and neutralize variant SIVs, we compared the kinetic rates and affinity of antibody binding to soluble envelope trimers by using surface plasmon resonance. We identified significant differences in the kinetic rates but not the affinity of monoclonal antibody binding to the neutralization-sensitive SIV/17E-CL and neutralization-resistant SIVmac239 envelope proteins that correlated with the neutralization sensitivities of the corresponding virus strains. These results suggest for the first time that neutralization resistance may be related to quantitative differences in the rates but not the affinity of the antibody-envelope interaction and may provide one mechanism for the inherent resistance of SIVmac239 to neutralization in vitro. Further, we provide evidence that factors in addition to antibody binding, such as epitope specificity, contribute to the mechanisms of neutralization of SIV/17E-CL in vitro. This study will impact the method by which HIV/SIV vaccines are evaluated and will influence the design of candidate AIDS vaccines capable of eliciting effective neutralizing antibody responses.
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页码:12311 / 12320
页数:10
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