Show simple item record

dc.contributor.authorBachler, Barbara Cen_US
dc.contributor.authorHumbert, Michaelen_US
dc.contributor.authorLakhashe, Samir Ken_US
dc.contributor.authorRasmussen, Robert Aen_US
dc.contributor.authorRuprecht, Ruth Men_US
dc.date.accessioned2014-02-13T19:01:55Z
dc.date.issued2013en_US
dc.identifier.citationBachler, Barbara C, Michael Humbert, Samir K Lakhashe, Robert A Rasmussen, and Ruth M Ruprecht. 2013. “Live-virus exposure of vaccine-protected macaques alters the anti-HIV-1 antibody repertoire in the absence of viremia.” Retrovirology 10 (1): 63. doi:10.1186/1742-4690-10-63. http://dx.doi.org/10.1186/1742-4690-10-63.en
dc.identifier.issn1742-4690en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:11708643
dc.description.abstractBackground: We addressed the question whether live-virus challenges could alter vaccine-induced antibody (Ab) responses in vaccinated rhesus macaques (RMs) that completely resisted repeated exposures to R5-tropic simian-human immunodeficiency viruses encoding heterologous HIV clade C envelopes (SHIV-Cs). Results: We examined the Ab responses in aviremic RMs that had been immunized with a multi-component protein vaccine (multimeric HIV-1 gp160, HIV-1 Tat and SIV Gag-Pol particles) and compared anti-Env plasma Ab titers before and after repeated live-virus exposures. Although no viremia was ever detected in these animals, they showed significant increases in anti-gp140 Ab titers after they had encountered live SHIVs. When we investigated the dynamics of anti-Env Ab titers during the immunization and challenge phases further, we detected the expected, vaccine-induced increases of Ab responses about two weeks after the last protein immunization. Remarkably, these titers kept rising during the repeated virus challenges, although no viremia resulted. In contrast, in vaccinated RMs that were not exposed to virus, anti-gp140 Ab titers declined after the peak seen two weeks after the last immunization. These data suggest boosting of pre-existing, vaccine-induced Ab responses as a consequence of repeated live-virus exposures. Next, we screened polyclonal plasma samples from two of the completely protected vaccinees by peptide phage display and designed a strategy that selects for recombinant phages recognized only by Abs present after – but not before – any SHIV challenge. With this “subtractive biopanning” approach, we isolated V3 mimotopes that were only recognized after the animals had been exposed to live virus. By detailed epitope mapping of such anti-V3 Ab responses, we showed that the challenges not only boosted pre-existing binding and neutralizing Ab titers, but also induced Abs targeting neo-antigens presented by the heterologous challenge virus. Conclusions: Anti-Env Ab responses induced by recombinant protein vaccination were altered by the multiple, live SHIV challenges in vaccinees that had no detectable viral loads. These data may have implications for the interpretation of “vaccine only” responses in clinical vaccine trials.en
dc.language.isoen_USen
dc.publisherBioMed Centralen
dc.relation.isversionofdoi:10.1186/1742-4690-10-63en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3695773/pdf/en
dash.licenseLAAen_US
dc.subjectMacaque modelen
dc.subjectRecombinant protein vaccineen
dc.subjectHeterologous R5 SHIV clade C challengeen
dc.subjectComplete protectionen
dc.subjectSubtractive peptide phage displayen
dc.subjectV3 crownen
dc.subjectBoosting of vaccine-induced Ab titers after multiple challengesen
dc.subjectNeo-antigen reactivityen
dc.titleLive-virus exposure of vaccine-protected macaques alters the anti-HIV-1 antibody repertoire in the absence of viremiaen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalRetrovirologyen
dash.depositing.authorHumbert, Michaelen_US
dc.date.available2014-02-13T19:01:55Z
dc.identifier.doi10.1186/1742-4690-10-63*
dash.contributor.affiliatedHumbert, Michael
dash.contributor.affiliatedRuprecht, Ruth Margrit


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record