title: Antibody-dependent cell-mediated viral inhibition emerges after simian immunodeficiency virus SIVmac251 infection of rhesus monkeys coincident with gp140-binding antibodies and is effective against neutralization-resistant viruses.
abstract: Antibody-dependent cell-mediated viral inhibition (ADCVI) is an attractive target for vaccination because it takes advantage of both the anamnestic properties of an adaptive immune response and the rapid early response characteristics of an innate immune response. Effective utilization of ADCVI in vaccine strategies will depend on an understanding of the natural history of ADCVI during acute and chronic human immunodeficiency virus type 1 (HIV-1) infection. We used the simian immunodeficiency virus (SIV)-infected rhesus monkey as a model to study the kinetics of ADCVI in early infection, the durability of ADCVI through the course of infection, and the effectiveness of ADCVI against viruses with envelope mutations that are known to confer escape from antibody neutralization. We demonstrate the development of ADCVI, capable of inhibiting viral replication 100-fold, within 3 weeks of infection, preceding the development of a comparable-titer neutralizing antibody response by weeks to months. The emergence of ADCVI was temporally associated with the emergence of gp140-binding antibodies, and in most animals, ADCVI persisted through the course of infection. Highly evolved viral envelopes from viruses isolated at late time points following infection that were resistant to plasma neutralization remained susceptible to ADCVI, suggesting that the epitope determinants of neutralization escape are not shared by antibodies that mediate ADCVI. These findings suggest that despite the ability of SIV to mutate and adapt to multiple immunologic pressures during the course of infection, SIV envelope may not escape the binding of autologous antibodies that mediate ADCVI.
authors: Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA. masmal@bidmc.harvard.edu
authors: Mohammed
authors: M
authors: Asmal
authors: Yue
authors: Y
authors: Sun
authors: Sophie
authors: S
authors: Lane
authors: Wendy
authors: W
authors: Yeh
authors: Stephen D
authors: SD
authors: Schmidt
authors: John R
authors: JR
authors: Mascola
authors: Norman L
authors: NL
authors: Letvin
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D000920:Antibody-Dependent Cell Cytotoxicity; D008253:Macaca mulatta; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D013997:Time Factors; D014759:Viral Envelope Proteins / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D014759:Viral Envelope Proteins