McKenna Philip M, Aye Pyone Pyone, Dietzschold Bernhard, Montefiori David C, Martin Louis N, Marx Preston A, Pomerantz Roger J, Lackner Andrew, Schnell Matthias J
Department of Microbiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA, USA.
J Virol. 2004 Dec;78(24):13455-9. doi: 10.1128/JVI.78.24.13455-13459.2004.
Rabies virus (RV) has recently been developed as a novel vaccine candidate for human immunodeficiency virus type 1 (HIV-1). The RV glycoprotein (G) can be functionally replaced by HIV-1 envelope glycoprotein (Env) if the gp160 cytoplasmic domain (CD) of HIV-1 Env is replaced by that of RV G. Here, we describe a pilot study of the in vivo replication and immunogenicity of an RV with a deletion of G (DeltaG) expressing a simian/human immunodeficiency virus SHIV(89.6P) Env ectodomain and transmembrane domain fused to the RV G CD (DeltaG-89.6P-RVG) in a rhesus macaque. An animal vaccinated with DeltaG-89.6P-RVG developed SHIV(89.6P) virus-neutralizing antibodies and SHIV(89.6P)-specific cellular immune responses after challenge with SHIV(89.6P). There was no evidence of CD4(+) T-cell loss, and plasma viremia was controlled to undetectable levels by 6 weeks postchallenge and has remained suppressed out to 22 weeks postchallenge.
狂犬病病毒(RV)最近已被开发成为一种用于1型人类免疫缺陷病毒(HIV-1)的新型候选疫苗。如果用RV G的gp160胞质结构域(CD)替换HIV-1 Env的gp160胞质结构域(CD),RV糖蛋白(G)在功能上可被HIV-1包膜糖蛋白(Env)取代。在此,我们描述了一项在恒河猴体内对缺失G(ΔG)并表达猿猴/人类免疫缺陷病毒SHIV(89.6P) Env胞外结构域和跨膜结构域且与RV G CD融合(ΔG-89.6P-RVG)的RV进行体内复制和免疫原性的初步研究。用ΔG-89.6P-RVG接种疫苗的动物在受到SHIV(89.6P)攻击后产生了SHIV(89.6P)病毒中和抗体和SHIV(89.6P)特异性细胞免疫反应。没有CD4(+) T细胞损失的证据,并且在攻击后6周时血浆病毒血症被控制在无法检测的水平,并且在攻击后22周一直保持被抑制状态。