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

重组 MVA-prime 通过诱导生发中心的抗原特异性 B 细胞来引发中和抗体反应

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作者: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, Adria

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.

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