Rhesus macaques previously infected with simian/human immunodeficiency virus are protected from vaginal challenge with pathogenic SIVmac239

Abstract

A total of five rhesus macaques have each been infected by exposure to at least three intravaginal inoculations of SHIV 89.6. The SHIV 89.6 infection is characterized by a transient viremia that evokes humoral and cellular immune responses to HIV and SIV antigens, but disease does not develop in animals infected with SHIV 89.6. To determine if a previous infection with SHIV 89.6 by vaginal inoculation could protect animals from vaginal challenge with pathogenic SIV, all five animals were intravaginally inoculated twice with pathogenic SIV-mac239. After challenge, all of the SHIV-immunized animals had low or undetectable viral RNA levels in plasma compared to control animals. Three of the five of the SHIV-immunized animals remained virus isolation negative for more than 8 months, while two became virus isolation positive. The presence of SIV Gag-specific cytotoxic T lymphocytes in peripheral blood mononuclear cells and SIV-specific antibodies in cervicovaginal secretions at the time of challenge was associated with resistance to pathogenic SIV infection after vaginal challenge. These results suggest that protection from sexual transmission of HIV may be possible by effectively stimulating both humoral and cellular antiviral immunity in the systemic and genital mucosal immune compartments. MATERIALS AND METHODS Animals. All animals used in this study were captive-bred, mature, cycling female rhesus macaques (Macaca mulatta) from the California Regional Primate Research Center. Prior to their initial use, the animals were negative for antibodies to HIV-2, SIV, type D retrovirus, and simian T-cell leukemia virus type 1

Occult Systemic Infection and Persistent Simian Immunodeficiency Virus (SIV)-Specific CD4+-T-Cell Proliferative Responses in Rhesus Macaques That Were Transiently Viremic after Intravaginal Inoculation of SIV

“…This animal's sera were negative for SIV antibody in all other assays. Finally, the vaginal washes of 10 transiently viremic monkeys were tested for IgG and IgA antibodies to SIV by a sensitive ELISA technique (31), and all samples were negative at the low dilutions tested. Thus, there was no evidence for mucosal antiviral antibody production in these STV monkeys inoculated with SIV by the intravaginal route.…”

“…Detection of SIV by PCR amplification. Nested PCR was carried out on genomic DNA using gag-specific primer pairs in a DNA Thermal Cycler (Perkin-Elmer Cetus, Emeryville, Calif.), using a previously described technique (31). This PCR protocol was found to be more sensitive than the one used in the initial report of STV animals (30).…”

“…Western blotting of serum samples with SIV antigen was performed as described (45). Vaginal wash samples were collected and assayed for SIV-specific immunoglobulin G (IgG) and IgA as previously described (31). Vaginal washes consist of a mixture of cervical and vaginal secretions and were collected by vigorously infusing 6 ml of sterile phosphate-buffered saline into the vaginal canal and aspirating as much of the instilled volume as possible.…”

Depo‐Provera abrogates attenuated lentivirus‐induced protection in male rhesus macaques challenged intravenously with pathogenic SIVmac239

“…The pathogenic SIVmac239 stock used in the present study was produced in rhesus peripheral blood mononuclear cells (PBMC) as previously described [23] and contained approximately 105 TCID50/ml. The virus challenge of the monkeys consisted of a single IV inoculation with 1 ml of the SIVmac239 stock diluted 1:100 in sterile saline to produce an inoculum containing 103 TCID50.…”

Mucosal immunity and tolerance: relevance to vaccine development

“…Recent studies in this mode! have provided direct evidence that pCTLs occur in female macaque reproductive tis.sues, and that infection with SIV induces effector CTL responses in the vaginal mucosa (41), Interestingly, macaques vaginally infected with an SIY/HIV-l cliimeric virus (SHIV) displayed gag-specific CTLs in peripheral blood and resisted two challenges with virulent SIV (42).…”