Partial Protection of SHIV-Infected Chinese Rhesus Macaques Against Super-Infection with Heterologous SHIV Isolate

Yue      Li; Qiang      Liu; Zhenwu      Luo; Yanmeng      Feng; Zhe      Li; Qiang      Wei; Yiming      Shao

Abstract

Background: Many studies have revealed a protective effect of infection with simian immunodeficiency virus (SIV) or simian-human immunodeficiency virus (SHIV) against subsequent infection by a related immunodeficiency virus. However, whether a protective response can be induced by an infection with an immunodeficiency virus is still currently debated in the HIV-1 vaccine field. The aim of this study was to evaluate the protection against SHIV challenge in Chinese macaques that had been inoculated with SHIVs containing different HIV-1 envelops.

Methods: Eleven adult Chinese rhesus monkeys were inoculated with SHIV-KB9, SHIV-1157ipd3N4 or SHIV-CN97001. After 30 weeks, the animals were exposed to SHIV-KB9 or SHIV-CN97001, which carried a heterologous envelope protein relative to the first challenge strain. Infection was monitored by measuring viral load and antibody response, as well as viral genome sequence analyses.

Results: After first challenge, all the monkeys demonstrated high viral loads and specific antibody responses. Protection from super-infection was statistically significant in all the animals inoculated with SHIV-KB9 or SHIV-1157ipd3N4. However, animals inoculated with SHIV-CN97001 and challenged with SHIV-KB9 showed new infections. The susceptibility to super-infection was not correlated with neutralizing antibodies present at the time of exposure to the second virus.

Conclusions: These findings indicate that different SHIV infection may confer different levels of protection against a second SHIV infection in Chinese monkeys. Understanding this protective response in SHIV infected macaques may shed a new light on HIV-1 vaccine development.

Keywords: SHIV, Chinese rhesus macaque, super-infection, protection, SHIV-KB9, SHIV-CN97001, CD4+, HIV, antibodies, 293T cells