Recombinant MVA-prime elicits neutralizing antibody responses by inducing antigen-specific B cells in the germinal center
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.
Eslamizar, L; Petrovas, C; Leggat, DJ; Furr, K; Lifton, ML; Levine, G; Ma, S; Fletez-Brant, C; Hoyland, W; Prabhakaran, M; Narpala, S; Boswell, K; Yamamoto, T; Liao, HX; Pickup, D; Ramsburg, E; Sutherland, L; McDermott, A; Roederer, M; Montefiori, D; Koup, RA; Haynes, BF; Letvin, NL; Santra, S
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