开发一种1级R5 C亚型猿猴-人类免疫缺陷病毒作为测试基于中和抗体的免疫预防的工具。
Development of a tier 1 R5 clade C simian-human immunodeficiency virus as a tool to test neutralizing antibody-based immunoprophylaxis.
作者信息
Siddappa Nagadenahalli B, Hemashettar Girish, Wong Yin Ling, Lakhashe Samir, Rasmussen Robert A, Watkins Jennifer D, Novembre Francis J, Villinger François, Else James G, Montefiori David C, Ruprecht Ruth M
机构信息
Dana-Farber Cancer Institute, Boston, MA 02115, USA.
出版信息
J Med Primatol. 2011 Apr;40(2):120-8. doi: 10.1111/j.1600-0684.2010.00454.x. Epub 2010 Nov 2.
Abstract
BACKGROUND
While some recently transmitted HIV clade C (HIV-C) strains exhibited tier 1 neutralization phenotypes, most were tier 2 strains (J Virol 2010; 84:1439). Because induction of neutralizing antibodies (nAbs) through vaccination against tier 2 viruses has proven difficult, we have generated a tier 1, clade C simian-human immunodeficiency virus (SHIV-C) to permit efficacy testing of candidate AIDS vaccines against tier 1 viruses.
METHODS
SHIV-1157ipEL was created by swapping env of a late-stage virus with that of a tier 1, early form.
RESULTS
After adaptation to rhesus macaques (RM), passaged SHIV-1157ipEL-p replicated vigorously in vitro and in vivo while maintaining R5 tropism. The virus was reproducibly transmissible intrarectally. Phylogenetically, SHIV-1157ipEL-p Env clustered with HIV-C sequences. All RM chronically infected with SHIV-1157ipEL-p developed high nAb titers against autologous as well as heterologous tier 1 strains.
CONCLUSIONS
SHIV-1157ipEL-p was reproducibly transmitted in RM, induced cross-clade nAbs, and represents a tool to evaluate anti-HIV-C nAb responses in primates.
摘要
背景
虽然一些近期传播的HIV C亚型（HIV-C）毒株表现出1级中和表型，但大多数是2级毒株（《病毒学杂志》2010年；84:1439）。由于通过接种疫苗诱导针对2级病毒的中和抗体（nAbs）已被证明很困难，我们构建了一种1级C亚型猿猴 - 人免疫缺陷病毒（SHIV-C），以允许对候选艾滋病疫苗针对1级病毒进行功效测试。
方法
通过将晚期病毒的env与1级早期形式的env进行交换，构建了SHIV-1157ipEL。
结果
在适应恒河猴（RM）后，传代的SHIV-1157ipEL-p在体外和体内均能旺盛复制，同时保持R5嗜性。该病毒可经直肠反复传播。在系统发育上，SHIV-1157ipEL-p Env与HIV-C序列聚类。所有长期感染SHIV-1157ipEL-p的恒河猴均产生了针对自体以及异源1级毒株的高nAb滴度。
结论
SHIV-1157ipEL-p在恒河猴中可反复传播，诱导跨亚型nAbs，代表了一种在灵长类动物中评估抗HIV-C nAb反应的工具。
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