Recombinant MVA-prime elicits neutralizing antibody responses by inducing antigen-specific B cells in the germinal center

Abstract The RV144 HIV-1 vaccine trial has been the only clinical trial to date that has shown any degree of efficacy and associated with the presence of vaccine-elicited HIV-1 envelope-specific binding antibody and CD4+ T-cell responses. This trial also showed that a vector-prime protein boost comb...

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Autores principales: Leila Eslamizar, Constantinos Petrovas, David J. Leggat, Kathryn Furr, Michelle L. Lifton, Gail Levine, Steven Ma, Christopher Fletez-Brant, Wesley Hoyland, Madhu Prabhakaran, Sandeep Narpala, Kristin Boswell, Takuya Yamamoto, Hua-Xin Liao, David Pickup, Elizabeth Ramsburg, Laura Sutherland, Adrian McDermott, Mario Roederer, David Montefiori, Richard A. Koup, Barton F. Haynes, Norman L. Letvin, Sampa Santra
Formato: article
Lenguaje:EN
Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/63b38173c836479fba679161167f0413
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Sumario:Abstract The RV144 HIV-1 vaccine trial has been the only clinical trial to date that has shown any degree of efficacy and associated with the presence of vaccine-elicited HIV-1 envelope-specific binding antibody and CD4+ T-cell responses. This trial also showed that a vector-prime protein boost combined vaccine strategy was better than when used alone. Here we have studied three different priming vectors—plasmid DNA, recombinant MVA, and recombinant VSV, all encoding clade C transmitted/founder Env 1086 C gp140, for priming three groups of six non-human primates each, followed by a protein boost with adjuvanted 1086 C gp120 protein. Our data showed that MVA-priming favors the development of higher antibody binding titers and neutralizing activity compared with other vectors. Analyses of the draining lymph nodes revealed that MVA-prime induced increased germinal center reactivity characterized by higher frequencies of germinal center (PNAhi) B cells, higher frequencies of antigen-specific B-cell responses as well as an increased frequency of the highly differentiated (ICOShiCD150lo) Tfh-cell subset.