Comparison of in vitro and in vivo infectivity of different clade B HIV-1 envelope chimeric Simian/Human immunodeficiency viruses in macaca mulatta

Abstract

The use of HIV-1 env/SIV(mac) chimeric viruses expressing divergent HIV-1 envelopes of clinical isolates, facilitates homologous and heterologous evaluation of various recombinant HIV-1 envelope vaccine candidates in lower primates. In this study we compare the in vitro and in vivo infectivity, via intravenous (IV) and intravaginal (IVAG) routes of infection, of stocks of chimeric viruses expressing env from four different clade B HIV-1 isolates. The TCID50/ml was 7.1 x 104, 1.0 x 104, 6.3 X 104, and 1.2 X 103 for SHIV(sf13) SHIV(Han2) SHIV(NM-3rn) and SHIV(W6.1D), respectively, with a MID50/ml upon IV inoculation of 3.2 X 103, 3.2 X 104, 3.2 X 104, and 3.2 X 103, respectively. The same SHIV(sf13) stock was infectious after IVAG administration, requiring a 300-fold higher virus dose. Plasma antigenemia and cell-associated viremia were generally highest at weeks 2 or 4 after infection and decreased to subdetectable levels after 8-12 weeks. All infected animals tested developed anti HIV-1 gp120 antibodies. Inoculated virus dose showed no (linear) quantitative correlation with cellular virus load, duration of viremia, plasma antigenemia, and anti-gp120 antibody titers. No significant changes in peripheral blood CD4 cell levels were observed and none of the animals has shown evidence of disease progression to date (i.e., 13 months postinfection). Four in vivo passages of cell-associated SHIV(W6.1D) did not result in increased virulence. Vaccine development studies in macaques monkeys have become feasible with the use of various clade B HIV-1 env SHIV chimeras.