Vaccine-Elicited Antibodies Mediate Antibody-Dependent Cellular Cytotoxicity Correlated with Significantly Reduced Acute Viremia in Rhesus Macaques Challenged with SIVmac251

Román, Raúl Gómez; Patterson, L. Jean; Venzon, David; Liewehr, David J.; Aldrich, Kris; Florese, Ruth H.; Robert-Guroff, Marjorie

doi:10.4049/jimmunol.174.4.2185

Cited by 260 publications

(238 citation statements)

References 41 publications

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“…Our experiments were not designed to elucidate an immunological mechanism for immunity by anti-CD4i epitope antibodies. However, likely possibilities include direct binding/neutralization of virions, complement-dependent cell lysis, and/or antibodydependent cellular cytotoxicity of infected cells, which have been correlated with the control of viremia (6). The abilities of human mAbs to anti-CD4i epitopes to bind envelope trimers before and after CD4 engagement (12,15,17,19,21,(31)(32)(33) and to recognize gp120 on the surface of freshly infected cells (19) are consistent with these possibilities.…”

Section: Discussionmentioning

confidence: 51%

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Antibodies to CD4-induced sites in HIV gp120 correlate with the control of SHIV challenge in macaques vaccinated with subunit immunogens

DeVico

Fouts

Lewis

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

109

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Epitopes located in and around the coreceptor binding site of HIV-1 envelope glycoprotein (gp120) exhibit enhanced exposure after attachment to the CD4 receptor and comprise some of the most conserved and functionally important residues on the viral envelope. Therefore, antibody responses to these epitopes [designated as CD4-induced (CD4i)] should be highly cross-reactive and potentially useful for HIV vaccine development. To address this question, rhesus macaques were vaccinated with subunit immunogens designed to raise humoral responses against CD4i epitopes and challenged rectally with SHIV 162P3, which encodes a heterologous envelope versus the immunogen. We found that animals vaccinated with a rhesus full-length single-chain (rhFLSC) complex exhibited significantly accelerated clearance of plasma viremia and an absence of long-term tissue viremia compared with unvaccinated control animals. Such control of infection correlated with stronger responses to CD4i epitopes in the rhFLSC-vaccinated animals, compared with macaques immunized with gp120, crosslinked gp120 -CD4 complexes, or soluble CD4 alone. These responses were strongly boosted in the rhFLSC-vaccinated animals by SHIV 162P3 infection. The control of infection was not associated with anti-CD4 responses, overall anti-gp120-binding titers, or neutralizing activity measured in conventional assays. Vaccine-naive animals also developed anti-CD4i epitope responses after simian/ human immunodeficiency virus (SHIV) challenge, which appeared later than the overall anti-gp120 responses and in concert with the decline of viremia to a low set point. Collectively, these data suggest that antibodies to CD4i epitopes may play a role in controlling SHIV infection and provide insights for HIV vaccine development.vaccine ͉ infection ͉ immunity

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Section: Discussionmentioning

confidence: 51%

“…Moreover, certain vaccine strategies are more effective in suppressing infection in nonhuman primate models when viral envelope is included in the vaccine (4,5). Recent evidence indicates that anti-envelope antibody-dependent cellular cytotoxicity activity correlates with protection against HIV challenge (6).…”

mentioning

confidence: 99%

Antibodies to CD4-induced sites in HIV gp120 correlate with the control of SHIV challenge in macaques vaccinated with subunit immunogens

DeVico

Fouts

Lewis

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

109

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“…Nonneutralizing anti-SIV-Ab that prevents infection of neonatal macaques after oral SIV mac251 challenge has potent ADCVI activity (13); in the absence of other Ab functions, it is likely that ADCVI accounted for this protection. Recently, a vaccine-induced reduction in acute SIV viremia was shown to correlate with the ADCC Ab response to the vaccine (32). Death of infected target cells by ADCC is one of the mechanisms by which ADCVI inhibits HIV-1 (11).…”

Section: Discussionmentioning

confidence: 99%

Recombinant gp120 Vaccine-Induced Antibodies Inhibit Clinical Strains of HIV-1 in the Presence of Fc Receptor-Bearing Effector Cells and Correlate Inversely with HIV Infection Rate

Forthal

Gilbert

Landucci

et al. 2007

The Journal of Immunology

163

159

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Nonneutralizing Abs may play a role in protecting animals and humans from lentiviral infections. We explored the Ab-dependent, cell-mediated virus inhibition (ADCVI) Ab response to recombinant gp120 (rgp120) vaccination in sera from 530 participants in the Vax 004 trial. Serum ADCVI activity was measured against a clinical R5 strain of HIV-1 using peripheral blood mononuclear effector cells from healthy donors. The level of vaccine-induced ADCVI activity correlated inversely with the rate of acquiring HIV infection following vaccination, such that for every 10% increase in ADCVI activity, there was a 6.3% decrease in the hazard rate of infection (p = 0.019). Some vaccinated individuals also mounted an ADCVI response against two other clinical R5 strains of HIV-1. However, ADCVI activity correlated poorly with neutralizing or CD4-gp120-blocking Ab activity measured against laboratory strains. Finally, the degree to which the ADCVI Ab response predicted the rate of infection was influenced by polymorphisms at the FcγRIIa and FcγRIIIa gene loci. These data indicate that rgp120 vaccination can elicit Abs with antiviral activity against clinical strains of HIV-1. However, such activity requires the presence of FcR-bearing effector cells. Our results provide further evidence that ADCVI may play a role in preventing HIV infection.

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“…3). Macaque simian immunodeficiency virus (SIV) vaccine studies and passive antibody transfer studies in recent years strongly suggest a role for ADCC in assisting protective immunity (4)(5)(6).…”

mentioning

confidence: 99%

Immune escape from HIV-specific antibody-dependent cellular cytotoxicity (ADCC) pressure

Chung

Isitman

Navis

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

131

132

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Effective immunity to HIV is poorly understood. In particular, a role for antibody-dependent cellular cytotoxicity (ADCC) in controlling HIV is controversial. We hypothesized that significant pressure from HIV-specific ADCC would result in immune-escape variants. A series of ADCC epitopes in HIV-infected subjects to specific consensus strain HIV peptides were mapped using a flow cytometric assay for natural killer cell activation. We then compared the ADCC responses to the same peptide epitope derived from the concurrent HIV sequence(s) expressed in circulating virus. In 9 of 13 epitopes studied, ADCC antibodies were unable to recognize the concurrent HIV sequence. Our studies suggest ADCC responses apply significant immune pressure on the virus. This result has implications for the induction of ADCC responses by HIV vaccines.natural killer cells | viral evolution | neutralizing antibody

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Vaccine-Elicited Antibodies Mediate Antibody-Dependent Cellular Cytotoxicity Correlated with Significantly Reduced Acute Viremia in Rhesus Macaques Challenged with SIVmac251

Cited by 260 publications

References 41 publications

Antibodies to CD4-induced sites in HIV gp120 correlate with the control of SHIV challenge in macaques vaccinated with subunit immunogens

Antibodies to CD4-induced sites in HIV gp120 correlate with the control of SHIV challenge in macaques vaccinated with subunit immunogens

Recombinant gp120 Vaccine-Induced Antibodies Inhibit Clinical Strains of HIV-1 in the Presence of Fc Receptor-Bearing Effector Cells and Correlate Inversely with HIV Infection Rate

Immune escape from HIV-specific antibody-dependent cellular cytotoxicity (ADCC) pressure

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