NPJ Vaccines. 2021 Jan 25; 6(1):15.

PubMed ID: 33495459

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

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

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.