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Journal of Virology, October 2005, p. 12311-12320, Vol. 79, No. 19
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.19.12311-12320.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Kinetic Rates of Antibody Binding Correlate with Neutralization Sensitivity of Variant Simian Immunodeficiency Virus Strains{dagger}

Jonathan D. Steckbeck,1 Irina Orlov,3 Andrew Chow,3 Heather Grieser,1 Kenneth Miller,3 JoAnne Bruno,3 James E. Robinson,4 Ronald C. Montelaro,2 and Kelly Stefano Cole1*

Department of Medicine, Infectious Diseases Division,1 Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261,2 Biacore, Inc., Piscataway, New Jersey 08854,3 Department of Pediatrics, Tulane Medical Center, New Orleans, Louisiana 701124

Received 22 October 2004/ Accepted 28 May 2005

Increasing evidence suggests that an effective AIDS vaccine will need to elicit both broadly reactive humoral 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.

* Corresponding author. Mailing address: University of Pittsburgh School of Medicine, Department of Medicine, Infectious Diseases Division, 3550 Terrace Street, Scaife Hall, Suite 867, Pittsburgh, PA 15261. Phone: (412) 648-8583. Fax: (412) 648-8455. E-mail: stefcole{at}pitt.edu.

{dagger} Supplemental material for this article may be found at http://jvi.asm.org/.

Journal of Virology, October 2005, p. 12311-12320, Vol. 79, No. 19
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.19.12311-12320.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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