Optimal combinations of broadly neutralizing antibodies for prevention and treatment of HIV-1 Clade C infection

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dc.contributor.authorWagh, Kshitijen_ZA
dc.contributor.authorBhattacharya, Tanmoyen_ZA
dc.contributor.authorWilliamson, Carolynen_ZA
dc.contributor.authorRobles, Alexen_ZA
dc.contributor.authorBayne, Madeleineen_ZA
dc.contributor.authorGarrity, Jettaen_ZA
dc.contributor.authorRist, Michaelen_ZA
dc.contributor.authorRademeyer, Ceciliaen_ZA
dc.contributor.authorYoon, Hyejinen_ZA
dc.contributor.authorLapedes, Alanen_ZA
dc.contributor.authorGao, Hongmeien_ZA
dc.contributor.authorGreene, Kellien_ZA
dc.contributor.authorLouder, Mark Ken_ZA
dc.contributor.authorKong, Ruien_ZA
dc.contributor.authorKarim, Salim Abdoolen_ZA
dc.contributor.authorBurton, Dennis Ren_ZA
dc.contributor.authorBarouch, Dan Hen_ZA
dc.contributor.authorNussenzweig, Michel Cen_ZA
dc.contributor.authorMascola, John Ren_ZA
dc.contributor.authorMorris, Lynnen_ZA
dc.contributor.authorMontefiori, David Cen_ZA
dc.contributor.authorKorber, Betteen_ZA
dc.contributor.authorSeaman, Michael Sen_ZA
dc.date.accessioned2016-04-13T12:33:32Z
dc.date.available2016-04-13T12:33:32Z
dc.date.issued2016en_ZA
dc.description.abstractAuthor Summary In recent years, a new generation of monoclonal antibodies has been isolated from HIV-1 infected individuals that exhibit broad and potent neutralizing activity when tested against diverse strains of virus. There is a high level of interest in the field in determining if these antibodies can be used to prevent or treat HIV-1 infection. Because HIV-1 is adept at escaping from immune recognition, it is generally thought that combinations of multiple antibodies targeting different sites will be required for efficacy, much the same as seen for conventional antiretroviral drugs. How many and which antibodies to include in such combinations is not known. In this study, a new mathematical model was developed and used to accurately predict various measures of neutralizing activity for all possible combinations having a total of 2, 3, or 4 of the most promising antibodies. Through a systematic and comprehensive comparison, we identified optimal combinations of antibodies that best complement one another for enhanced anti-viral activity, and therefore may be most effective for the prevention or treatment of HIV-1 infection. These results provide important parameters that inform the selection of antibodies to develop for clinical use.en_ZA
dc.identifier.apacitationWagh, K., Bhattacharya, T., Williamson, C., Robles, A., Bayne, M., Garrity, J., ... Seaman, M. S. (2016). Optimal combinations of broadly neutralizing antibodies for prevention and treatment of HIV-1 Clade C infection. <i>PLoS One</i>, http://hdl.handle.net/11427/18849en_ZA
dc.identifier.chicagocitationWagh, Kshitij, Tanmoy Bhattacharya, Carolyn Williamson, Alex Robles, Madeleine Bayne, Jetta Garrity, Michael Rist, et al "Optimal combinations of broadly neutralizing antibodies for prevention and treatment of HIV-1 Clade C infection." <i>PLoS One</i> (2016) http://hdl.handle.net/11427/18849en_ZA
dc.identifier.citationWagh, K., Bhattacharya, T., Williamson, C., Robles, A., Bayne, M., Garrity, J., ... & Gao, H. (2016). Optimal combinations of broadly neutralizing antibodies for prevention and treatment of HIV-1 Clade C infection. PLoS Pathog, 12(3), e1005520. doi:10.1371/journal.ppat.1005520en_ZA
dc.identifier.ris TY - Journal Article AU - Wagh, Kshitij AU - Bhattacharya, Tanmoy AU - Williamson, Carolyn AU - Robles, Alex AU - Bayne, Madeleine AU - Garrity, Jetta AU - Rist, Michael AU - Rademeyer, Cecilia AU - Yoon, Hyejin AU - Lapedes, Alan AU - Gao, Hongmei AU - Greene, Kelli AU - Louder, Mark K AU - Kong, Rui AU - Karim, Salim Abdool AU - Burton, Dennis R AU - Barouch, Dan H AU - Nussenzweig, Michel C AU - Mascola, John R AU - Morris, Lynn AU - Montefiori, David C AU - Korber, Bette AU - Seaman, Michael S AB - Author Summary In recent years, a new generation of monoclonal antibodies has been isolated from HIV-1 infected individuals that exhibit broad and potent neutralizing activity when tested against diverse strains of virus. There is a high level of interest in the field in determining if these antibodies can be used to prevent or treat HIV-1 infection. Because HIV-1 is adept at escaping from immune recognition, it is generally thought that combinations of multiple antibodies targeting different sites will be required for efficacy, much the same as seen for conventional antiretroviral drugs. How many and which antibodies to include in such combinations is not known. In this study, a new mathematical model was developed and used to accurately predict various measures of neutralizing activity for all possible combinations having a total of 2, 3, or 4 of the most promising antibodies. Through a systematic and comprehensive comparison, we identified optimal combinations of antibodies that best complement one another for enhanced anti-viral activity, and therefore may be most effective for the prevention or treatment of HIV-1 infection. These results provide important parameters that inform the selection of antibodies to develop for clinical use. DA - 2016 DB - OpenUCT DO - 10.1371/journal.ppat.1005520 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2016 T1 - Optimal combinations of broadly neutralizing antibodies for prevention and treatment of HIV-1 Clade C infection TI - Optimal combinations of broadly neutralizing antibodies for prevention and treatment of HIV-1 Clade C infection UR - http://hdl.handle.net/11427/18849 ER - en_ZA
dc.identifier.urihttp://dx.doi.org/10.1371/journal.ppat.1005520en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/18849
dc.identifier.vancouvercitationWagh K, Bhattacharya T, Williamson C, Robles A, Bayne M, Garrity J, et al. Optimal combinations of broadly neutralizing antibodies for prevention and treatment of HIV-1 Clade C infection. PLoS One. 2016; http://hdl.handle.net/11427/18849.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentDivision of Virologyen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLoS Oneen_ZA
dc.source.urihttp://journals.plos.org/plospathogensen_ZA
dc.subject.otherHIV-1en_ZA
dc.subject.otherAntibodiesen_ZA
dc.subject.otherAntiretroviralsen_ZA
dc.subject.otherComplement systemen_ZA
dc.subject.otherImmunotherapyen_ZA
dc.subject.otherBlood plasmaen_ZA
dc.subject.otherMicrobial geneticsen_ZA
dc.subject.otherPharmacokineticsen_ZA
dc.titleOptimal combinations of broadly neutralizing antibodies for prevention and treatment of HIV-1 Clade C infectionen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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