Comparison ofin Vitroandin VivoInfectivity of Different Clade B HIV-1 Envelope Chimeric Simian/Human Immunodeficiency Viruses inMacaca mulatta

Abstract

The use of HIV-1env/SIVmacchimeric 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 thein vitroandin vivoinfectivity, via intravenous (IV) and intravaginal (IVAG) routes of infection, of stocks of chimeric viruses expressingenvfrom four different clade B HIV-1 isolates. The TCID50/ml was 7.1 × 104, 1.0 × 104, 6.3 × 104, and 1.2 × 103for SHIVsf13, SHIVHan2, SHIVNM-3rn, and SHIVW6.1D, respectively, with a MID50/ml upon IV inoculation of 3.2 × 103, 3.2 × 104, 3.2 × 104, and 3.2 × 103, respectively. The same SHIVsf13stock 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). Fourin vivopassages of cell-associated SHIVW6.1Ddid not result in increased virulence. Vaccine development studies in macaques monkeys have become feasible with the use of various clade B HIV-1envSHIV chimeras.