Identification of broadly neutralizing antibody epitopes in the HIV-1 envelope glycoprotein using evolutionary models

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dc.contributor.authorLacerda, Miguelen_ZA
dc.contributor.authorMoore, Penny L.en_ZA
dc.contributor.authorNgandu, Nobubelo K.en_ZA
dc.contributor.authorSeaman, Michaelen_ZA
dc.contributor.authorGray, Elin S.en_ZA
dc.contributor.authorMurrell, Benen_ZA
dc.contributor.authorKrishnamoorthy, Mohanen_ZA
dc.contributor.authorNonyane, Molatien_ZA
dc.contributor.authorMadiga, Maphutien_ZA
dc.contributor.authorWibmer, Constantinos K.en_ZA
dc.contributor.authorSheward, Danielen_ZA
dc.contributor.authorBailer, Robert T.en_ZA
dc.contributor.authorGao, Hongmeien_ZA
dc.contributor.authorGreene, Kelli M.en_ZA
dc.contributor.authorKarim, Salim S. A.en_ZA
dc.contributor.authorMascola, John R.en_ZA
dc.contributor.authorKorber, Bette T. M.en_ZA
dc.contributor.authorMontefiori, David C.en_ZA
dc.contributor.authorMorris, Lynnen_ZA
dc.contributor.authorWilliamson, Carolynen_ZA
dc.contributor.authorSeoighe, Cathalen_ZA
dc.contributor.authorthe CAVD-NSDP Consortiumen_ZA
dc.date.accessioned2014-09-17T08:26:12Z
dc.date.available2014-09-17T08:26:12Z
dc.date.issued2013-12-02
dc.date.updated2014-04-05T15:21:57Z
dc.descriptionCITATION: Lacerda, M. et al. 2013. Identification of broadly neutralizing antibody epitopes in the HIV-1 envelope glycoprotein using evolutionary models. Virology Journal, 10:347: doi:10.1186/1743-422X-10-347.en_ZA
dc.descriptionThe original publication is available at http://www.virologyj.com/content/10/1/347en_ZA
dc.description.abstractBackground Identification of the epitopes targeted by antibodies that can neutralize diverse HIV-1 strains can provide important clues for the design of a preventative vaccine. Methods We have developed a computational approach that can identify key amino acids within the HIV-1 envelope glycoprotein that influence sensitivity to broadly cross-neutralizing antibodies. Given a sequence alignment and neutralization titers for a panel of viruses, the method works by fitting a phylogenetic model that allows the amino acid frequencies at each site to depend on neutralization sensitivities. Sites at which viral evolution influences neutralization sensitivity were identified using Bayes factors (BFs) to compare the fit of this model to that of a null model in which sequences evolved independently of antibody sensitivity. Conformational epitopes were identified with a Metropolis algorithm that searched for a cluster of sites with large Bayes factors on the tertiary structure of the viral envelope. Results We applied our method to ID50 neutralization data generated from seven HIV-1 subtype C serum samples with neutralization breadth that had been tested against a multi-clade panel of 225 pseudoviruses for which envelope sequences were also available. For each sample, between two and four sites were identified that were strongly associated with neutralization sensitivity (2ln(BF) > 6), a subset of which were experimentally confirmed using site-directed mutagenesis. Conclusions Our results provide strong support for the use of evolutionary models applied to cross-sectional viral neutralization data to identify the epitopes of serum antibodies that confer neutralization breadth.en_ZA
dc.description.versionPublishers' versionen_ZA
dc.identifier.citationLacerda, M. et al. 2013. Identification of broadly neutralizing antibody epitopes in the HIV-1 envelope glycoprotein using evolutionary models. Virology Journal, 10:347: doi:10.1186/1743-422X-10-347.en_ZA
dc.identifier.issn1743-422X (online)
dc.identifier.otherdoi:10.1186/1743-422X-10-347
dc.identifier.urihttp://dx.doi.org/10.1186/1743-422X-10-347
dc.identifier.urihttp://hdl.handle.net/10019.1/95581
dc.language.isoen_ZAen_ZA
dc.publisherBioMed Centralen_ZA
dc.rights.holderMiguel Lacerda et al.; licensee BioMed Central Ltd.en_ZA
dc.subjectHIV infections -- Preventionen_ZA
dc.subjectHIV (Viruses) -- Computer simulationen_ZA
dc.subjectAIDS vaccinesen_ZA
dc.subjectViral antibodiesen_ZA
dc.subjectAntigenic determinants (epitopes)en_ZA
dc.subjectNeutralization (Chemistry)en_ZA
dc.titleIdentification of broadly neutralizing antibody epitopes in the HIV-1 envelope glycoprotein using evolutionary modelsen_ZA
dc.typeArticleen_ZA
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