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dc.contributor.authorSholukh, Anton Men_US
dc.contributor.authorByrareddy, Siddappa Nen_US
dc.contributor.authorShanmuganathan, Vivekanandanen_US
dc.contributor.authorHemashettar, Girishen_US
dc.contributor.authorLakhashe, Samir Ken_US
dc.contributor.authorRasmussen, Robert Aen_US
dc.contributor.authorWatkins, Jennifer Den_US
dc.contributor.authorVyas, Hemant Ken_US
dc.contributor.authorThorat, Swatien_US
dc.contributor.authorBrandstoetter, Taniaen_US
dc.contributor.authorMukhtar, Muhammad Men_US
dc.contributor.authorYoon, John Ken_US
dc.contributor.authorNovembre, Francis Jen_US
dc.contributor.authorVillinger, Francoisen_US
dc.contributor.authorLanducci, Garyen_US
dc.contributor.authorForthal, Donald Nen_US
dc.contributor.authorRatcliffe, Sarahen_US
dc.contributor.authorTuero, Iskraen_US
dc.contributor.authorRobert-Guroff, Marjorieen_US
dc.contributor.authorPolonis, Victoria Ren_US
dc.contributor.authorBilska, Miroslawaen_US
dc.contributor.authorMontefiori, David Cen_US
dc.contributor.authorJohnson, Welkin Een_US
dc.contributor.authorErtl, Hildegund Cen_US
dc.contributor.authorRuprecht, Ruth Men_US
dc.date.accessioned2014-03-11T13:27:29Z
dc.date.issued2014en_US
dc.identifier.citationSholukh, A. M., S. N. Byrareddy, V. Shanmuganathan, G. Hemashettar, S. K. Lakhashe, R. A. Rasmussen, J. D. Watkins, et al. 2014. “Passive immunization of macaques with polyclonal anti-SHIV IgG against a heterologous tier 2 SHIV: outcome depends on IgG dose.” Retrovirology 11 (1): 8. doi:10.1186/1742-4690-11-8. http://dx.doi.org/10.1186/1742-4690-11-8.en
dc.identifier.issn1742-4690en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:11879668
dc.description.abstractBackground: A key goal for HIV-1 envelope immunogen design is the induction of cross-reactive neutralizing antibodies (nAbs). As AIDS vaccine recipients will not be exposed to strains exactly matching any immunogens due to multiple HIV-1 quasispecies circulating in the human population worldwide, heterologous SHIV challenges are essential for realistic vaccine efficacy testing in primates. We assessed whether polyclonal IgG, isolated from rhesus monkeys (RMs) with high-titer nAbs (termed SHIVIG), could protect RMs against the R5-tropic tier-2 SHIV-2873Nip, which was heterologous to the viruses or HIV-1 envelopes that had elicited SHIVIG. Results: SHIVIG demonstrated binding to HIV Gag, Tat, and Env of different clades and competed with the broadly neutralizing antibodies b12, VRC01, 4E10, and 17b. SHIVIG neutralized tier 1 and tier 2 viruses, including SHIV-2873Nip. NK-cell depletion decreased the neutralizing activity of SHIVIG 20-fold in PBMC assays. Although SHIVIG neutralized SHIV-2873Nip in vitro, this polyclonal IgG preparation failed to prevent acquisition after repeated intrarectal low-dose virus challenges, but at a dose of 400 mg/kg, it significantly lowered peak viremia (P = 0.001). Unexpectedly, single-genome analysis revealed a higher number of transmitted variants at the low dose of 25 mg/kg, implying increased acquisition at low SHIVIG levels. In vitro, SHIVIG demonstrated complement-mediated Ab-dependent enhancement of infection (C’-ADE) at concentrations similar to those observed in plasmas of RMs treated with 25 mg/kg of SHIVIG. Conclusion: Our primate model data suggest a dual role for polyclonal anti-HIV-1 Abs depending on plasma levels upon virus encounter.en
dc.language.isoen_USen
dc.publisherBioMed Centralen
dc.relation.isversionofdoi:10.1186/1742-4690-11-8en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3905655/pdf/en
dash.licenseLAAen_US
dc.subjectMacaque modelen
dc.subjectHeterologous R5 SHIV clade C challengeen
dc.subjectSHIVIGen
dc.subjectPassive immunizationen
dc.subjectEnhancement of infectionen
dc.subjectNon-human primate modelen
dc.titlePassive immunization of macaques with polyclonal anti-SHIV IgG against a heterologous tier 2 SHIV: outcome depends on IgG doseen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalRetrovirologyen
dash.depositing.authorSholukh, Anton Men_US
dc.date.available2014-03-11T13:27:29Z
dc.identifier.doi10.1186/1742-4690-11-8*
dash.authorsorderedfalse
dash.contributor.affiliatedRuprecht, Ruth Margrit
dash.contributor.affiliatedVyas, Hemant Kumar
dash.contributor.affiliatedThorat, Swati
dash.contributor.affiliatedWatkins, Jennifer D.
dash.contributor.affiliatedLakhashe, Samir
dash.contributor.affiliatedSholukh, Anton M.


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