Journal
VIROLOGY
Volume 475, Issue -, Pages 37-45Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2014.10.032
Keywords
SHIV; HIV-1 Clade C; Transmitted/founder Env; Mucosal transmission
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Funding
- Center for HIV/AIDS Vaccine Immunology-Immunogen Design (CHAVI-ID) [UM1-AI00645]
- Bill and Melinda Gates Foundation [OPP1033104]
- NIH [HHSN272201100022C, HHSN2722013000013]
- Harvard University Center for AIDS Research grant NIH [P30-AI060354]
- New England Primate Research Center base grant NIH [OD011103]
- Bill and Melinda Gates Foundation [OPP1033104] Funding Source: Bill and Melinda Gates Foundation
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Simian-human immunodeficiency viruses (SHIVs) that mirror natural transmitted/founder (T/F) viruses in man are needed for evaluation of HIV-1 vaccine candidates in nonhuman primates. Currently available SHIVs contain HIV-1 any genes from chronically-infected individuals and do not reflect the characteristics of biologically relevant HIV-1 strains that mediate human transmission. We chose to develop clade C SHIVs, as clade C is the major infecting subtype of HIV-1 in the world. We constructed 10 clade C SHIVs expressing Env proteins from T/F viruses. Three of these ten clade C SHIVs (SHIV KB9 C3, SHIV KB9 C4 and SHIV KB9 C5) replicated in naive rhesus monkeys. These three SHIVs are mucosally transmissible and are neutralized by sCD4 and several HIV-1 broadly neutralizing antibodies. However, like natural T/F viruses, they exhibit low Env reactivity and a Tier 2 neutralization sensitivity. Of note, none of the clade C T/F SHIVs elicited detectable autologous neutralizing antibodies in the infected monkeys, even though antibodies that neutralized a heterologous Tier 1 HIV-1 were generated. Challenge with these three new clade C SHIVs will provide biologically relevant tests for vaccine protection in rhesus macaques. (C) 2014 Elsevier Inc. All rights reserved.
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