携带SIV gp140蛋白的Ad26/MVA疫苗及维沙托利莫德在接受抗逆转录病毒治疗的恒河猴中的治疗效果

Therapeutic efficacy of an Ad26/MVA vaccine with SIV gp140 protein and vesatolimod in ART-suppressed rhesus macaques.

作者信息

Ventura John D, Nkolola Joseph P, Chandrashekar Abishek, Borducchi Erica N, Liu Jinyan, Mercado Noe B, Hope David L, Giffin Victoria M, McMahan Katherine, Geleziunas Romas, Murry Jeffrey P, Yang Yunling, Lewis Mark G, Pau Maria G, Wegmann Frank, Schuitemaker Hanneke, Fray Emily J, Kumar Mithra R, Siliciano Janet D, Siliciano Robert F, Robb Merlin L, Michael Nelson L, Barouch Dan H

机构信息

Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA.

Gilead Sciences, Foster City, CA, 94404, USA.

出版信息

NPJ Vaccines. 2022 May 18;7(1):53. doi: 10.1038/s41541-022-00477-x.

Developing an intervention that results in virologic control following discontinuation of antiretroviral therapy (ART) is a major objective of HIV-1 cure research. In this study, we investigated the therapeutic efficacy of a vaccine consisting of adenovirus serotype 26 (Ad26) and modified vaccinia Ankara (MVA) with or without an SIV Envelope (Env) gp140 protein with alum adjuvant in combination with the TLR7 agonist vesatolimod (GS-9620) in 36 ART-suppressed, SIVmac251-infected rhesus macaques. Ad26/MVA therapeutic vaccination led to robust humoral and cellular immune responses, and the Env protein boost increased antibody responses. Following discontinuation of ART, virologic control was observed in 5/12 animals in each vaccine group, compared with 0/12 animals in the sham control group. These data demonstrate therapeutic efficacy of Ad26/MVA vaccination with vesatolimod but no clear additional benefit of adding an Env protein boost. SIV-specific cellular immune responses correlated with virologic control. Our findings show partial efficacy of therapeutic vaccination following ART discontinuation in SIV-infected rhesus macaques.

开发一种在抗逆转录病毒疗法（ART）中断后能实现病毒学控制的干预措施是HIV-1治愈研究的主要目标。在本研究中，我们调查了一种由26型腺病毒（Ad26）和安卡拉痘苗病毒（MVA）组成的疫苗的治疗效果，该疫苗含有或不含SIV包膜（Env）gp140蛋白并添加明矾佐剂，同时联合Toll样受体7激动剂维沙托利莫德（GS-9620），用于36只接受ART抑制、感染SIVmac251的恒河猴。Ad26/MVA治疗性疫苗接种引发了强烈的体液和细胞免疫反应，而Env蛋白加强免疫增强了抗体反应。在ART中断后，每个疫苗组中有5/12只动物实现了病毒学控制，相比之下，假手术对照组中为0/12只动物。这些数据证明了Ad26/MVA联合维沙托利莫德疫苗接种的治疗效果，但添加Env蛋白加强免疫没有明显的额外益处。SIV特异性细胞免疫反应与病毒学控制相关。我们的研究结果表明，在感染SIV的恒河猴中，ART中断后的治疗性疫苗接种具有部分疗效。