Wee Edmund G, Moyo Nathifa A, Saunders Kevin O, LaBranche Celia, Donati Filippo, Capucci Silvia, Parks Robert, Borthwick Nicola, Hannoun Zara, Montefiori David C, Haynes Barton F, Hanke Tomáš
The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7DQ, UK.
Department of Surgery, Duke University School of Medicine, Durham, NC 27710, USA.
Mol Ther Methods Clin Dev. 2019 Jun 29;14:148-160. doi: 10.1016/j.omtm.2019.06.003. eCollection 2019 Sep 13.
The aim of this work was to start collecting information on rational combination of antibody (Ab) and T cell vaccines into single regimens. Two promising candidate HIV-1 vaccine strategies, sequential isolates of CH505 virus Envs developed for initiation of broadly neutralizing antibody lineages and conserved-mosaic tHIVconsvX immunogens aiming to induce effective cross-clade T cell responses, were combined to assess vaccine interactions. These immunogens were delivered in heterologous vector/modality regimens consisting of non-replicating simian (chimpanzee) adenovirus ChAdOx1 (C), non-replicating poxvirus MVA (M), and adjuvanted protein (P). Outbred CD1-SWISS mice were vaccinated intramuscularly using either parallel CM8M (tHIVconsvX)/CPPP (CH505) or sequential CM16M (tHIVconsvX)/CPPP (CH505) protocols, the latter of which delivered T cell CM prior to the CH505 Env. CM8M (tHIVconsvX) and CPPP or CMMP (CH505) vaccinations alone were included as comparators. The vaccine-elicited HIV-1-specific trimer-binding and neutralizing Abs and CD8/CD4 T cell responses induced by the combined and comparator regimens were not statistically separable among regimens. The Ab-lineage immunogen strategy was particularly suited for combined regimens for its likely less potent induction of Env-specific T cell responses relative to homologous epitope-based vaccine strategies. These results inform design of the first rationally combined Ab and T cell vaccine regimens in human volunteers.
这项工作的目的是开始收集关于将抗体（Ab）和T细胞疫苗合理组合成单一方案的信息。将两种有前景的候选HIV-1疫苗策略相结合以评估疫苗相互作用，这两种策略分别是：为启动广泛中和抗体谱系而开发的CH505病毒Env的连续分离株，以及旨在诱导有效的跨亚型T细胞反应的保守镶嵌tHIVconsvX免疫原。这些免疫原通过由非复制型猿猴（黑猩猩）腺病毒ChAdOx1（C）、非复制型痘病毒MVA（M）和佐剂蛋白（P）组成的异源载体/剂型方案进行递送。使用平行的CM8M（tHIVconsvX）/CPPP（CH505）或序贯的CM16M（tHIVconsvX）/CPPP（CH505）方案对远交系CD1-SWISS小鼠进行肌肉注射，后者在CH505 Env之前递送T细胞CM。单独的CM8M（tHIVconsvX）和CPPP或CMMP（CH505）疫苗接种作为对照。联合方案和对照方案诱导的疫苗引发的HIV-1特异性三聚体结合和中和抗体以及CD8/CD4 T细胞反应在各方案之间没有统计学上的差异。相对于基于同源表位的疫苗策略，抗体谱系免疫原策略可能对Env特异性T细胞反应的诱导作用较弱，因此特别适合联合方案。这些结果为人类志愿者中首个合理组合的抗体和T细胞疫苗方案的设计提供了依据。
