Allan J S, Ray P, Broussard S, Whitehead E, Hubbard G, Butler T, Brasky K, Luciw P, Cheng-Mayer C, Levy J A
Department of Virology and Immunology, Southwest Foundation for Biomedical Research, San Antonio, TX 78228, USA.
J Acquir Immune Defic Syndr Hum Retrovirol. 1995 Aug 15;9(5):429-41.
Baboons were evaluated for their utility to serve as a model for testing envelope-based vaccines against human immunodeficiency virus type 1 (HIV-1). The ability of HIV-1 strains IIIB, RF, and SF2 to infect baboons was compared with that of simian/human immunodeficiency virus (SHIV) recombinant viruses comprised of either HXB2 or SF2 env, tat, rev, and vpu genes inserted into the SIVmac239 backbone. Both SHIV recombinants replicated in baboon PBMC in vitro, while no evidence of replication was noted for HIV-1 strains (MN, IIIB, SF2). Infection of baboons in vivo correlated with the restriction of infection in vitro. Virus was recovered by cocultivation methods early after SHIV (HXBc2) infection of two baboons with seroconversion profiles that parallel those observed in simian immunodeficiency virus (SIV)mac-infected rhesus monkeys. One of two baboons inoculated with SHIV(SF2) also seroconverted within 4 weeks; however, the kinetics of infection in a second animal appeared much later, with seroconversion to gp120 not evident until 20 weeks and no virus recovery during 32 weeks following infection. Viral DNA was detected in the lymph nodes of the SHIV-inoculated animals by nested polymerase chain reaction (PCR) amplification. Histopathologic changes were evident in lymph nodes, yet no overt clinical disease was observed. When HIV-1 strains (IIIB, RF, and SF2) were inoculated into baboons, virus was not recovered and no seroconversion to the major HIV-1 antigens was observed. However, viral DNA from the lymph nodes of four animals inoculated with HIV-1 strains could be detected by nested PCR, indicating a persistent but diminutive infection of HIV-1. The baboon thus represents a new animal model for testing HIV-1 envelope-based vaccines including the evaluation of new immunogens, dosages, routes, and adjuvants that act in eliciting protective responses.
对狒狒作为测试针对1型人类免疫缺陷病毒（HIV-1）的包膜疫苗的模型的实用性进行了评估。将HIV-1毒株IIIB、RF和SF2感染狒狒的能力与由插入SIVmac239主干的HXB2或SF2 env、tat、rev和vpu基因组成的猿猴/人类免疫缺陷病毒（SHIV）重组病毒的感染能力进行了比较。两种SHIV重组体在体外狒狒外周血单核细胞（PBMC）中均能复制，而未观察到HIV-1毒株（MN、IIIB、SF2）有复制迹象。狒狒体内感染情况与体外感染限制相关。在两只狒狒感染SHIV（HXBc2）后早期，通过共培养方法回收了病毒，其血清转化情况与感染猿猴免疫缺陷病毒（SIV）mac的恒河猴中观察到的情况相似。接种SHIV（SF2）的两只狒狒中有一只在4周内也发生了血清转化；然而，第二只动物的感染动力学出现得晚得多，直到20周才出现针对gp120的血清转化，感染后32周内未回收病毒。通过巢式聚合酶链反应（PCR）扩增在接种SHIV的动物淋巴结中检测到病毒DNA。淋巴结中有明显的组织病理学变化，但未观察到明显的临床疾病。当将HIV-1毒株（IIIB、RF和SF2）接种到狒狒体内时，未回收病毒，也未观察到针对主要HIV-1抗原的血清转化。然而，通过巢式PCR可以检测到接种HIV-1毒株的四只动物淋巴结中的病毒DNA，表明存在HIV-1的持续性但微弱的感染。因此，狒狒代表了一种新的动物模型，可用于测试基于HIV-1包膜的疫苗，包括评估新的免疫原、剂量、途径和在引发保护性反应中起作用的佐剂。
