Eslamizar Leila, Petrovas Constantinos, Leggat David J, Furr Kathryn, Lifton Michelle L, Levine Gail, Ma Steven, Fletez-Brant Christopher, Hoyland Wesley, Prabhakaran Madhu, Narpala Sandeep, Boswell Kristin, Yamamoto Takuya, Liao Hua-Xin, Pickup David, Ramsburg Elizabeth, Sutherland Laura, McDermott Adrian, Roederer Mario, Montefiori David, Koup Richard A, Haynes Barton F, Letvin Norman L, Santra Sampa
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Integrative Toxicology, Nonclinical Drug Safety, Boehringer Ingelheim Pharmaceuticals, Inc., 175 Briar Ridge Road, Ridgefield, CT, 06877, USA.
NPJ Vaccines. 2021 Jan 25;6(1):15. doi: 10.1038/s41541-020-00277-1.
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 (PNA) B cells, higher frequencies of antigen-specific B-cell responses as well as an increased frequency of the highly differentiated (ICOSCD150) Tfh-cell subset.
RV144 HIV-1疫苗试验是迄今为止唯一一项显示出一定程度疗效的临床试验，且与疫苗诱导的HIV-1包膜特异性结合抗体及CD4+ T细胞反应的存在相关。该试验还表明，载体初免-蛋白加强联合疫苗策略比单独使用时效果更好。在此，我们研究了三种不同的初免载体——质粒DNA、重组痘苗病毒 Ankara（MVA）和重组水疱性口炎病毒（VSV），它们均编码C亚型传播/奠基Env 1086 C gp140，分别对三组，每组六只非人灵长类动物进行初免，随后用佐剂化的1086 C gp120蛋白进行蛋白加强免疫。我们的数据表明，与其他载体相比，MVA初免更有利于产生更高的抗体结合滴度和中和活性。对引流淋巴结的分析显示，MVA初免诱导生发中心反应性增强，其特征为生发中心（PNA）B细胞频率更高、抗原特异性B细胞反应频率更高以及高分化（ICOSCD150）滤泡辅助性T细胞亚群频率增加。
