Simian-Human Immunodeficiency Virus SHIV89.6-Induced Protection against Intravaginal Challenge with Pathogenic SIVmac239 Is Independent of the Route of Immunization and Is Associated with a Combination of Cytotoxic T-Lymphocyte and Alpha Interferon Responses

High Beta-Chemokine Expression Levels in Lymphoid Tissues of Simian/Human Immunodeficiency Virus 89.6-Vaccinated Rhesus Macaques Are Associated with Uncontrolled Replication of Simian Immunodeficiency Virus Challenge Inoculum

“…All animals were negative for antibodies to HIV type 2, SIV, type D retrovirus, and simian T-cell lymphotropic virus type 1 at the time the study was initiated. The rhesus monkeys used for this study were part of a previously published vaccine study (1). A randomly selected subgroup of 31 monkeys from the original group of 42 was included in this study.…”

“…SHIV89.6-immunized or unvaccinated monkeys were challenged with at least two intravaginal inoculations of SIVmac239 (1 ml at 10 5 50% tissue culture infective doses/ml). This virus stock was produced in rhesus PBMC and was described previously (1).…”

“…However, live attenuated vaccines have consistently provided the most effective protection against a challenge with virulent SIV and they stimulate a broad range of antiviral immune responses in rhesus macaques (1,21). Many studies have found an association between the in vitro secretion of beta-chemokines by peripheral blood mononuclear cells (PBMC) and vaccine-mediated protection from SIV or SHIV challenge (3,5,24,29,30).…”

“…In an earlier study, members of our laboratory showed that approximately 60% of rhesus monkeys inoculated with attenuated SHIV89.6 were protected from uncontrolled viral replication and disease after an intravaginal challenge with pathogenic SIVmac239 (1,34). Strong antiviral CTL responses and alpha interferon expression in PBMC during the acute postchallenge period were associated with protection.…”

CD8 + Lymphocytes Do Not Mediate Protection against Acute Superinfection 20 Days after Vaccination with a Live Attenuated Simian Immunodeficiency Virus

“…An unambiguous correlate of protection against superinfection has so far evaded identification. Cytotoxic T lymphocytes (CTL), virus neutralizing antibodies, innate immunity, and retroviral interference have all been reported as potential mechanisms of protection against superinfection conferred by inoculation with live attenuated SIV (2,24,32,37,50,54,59). Here we have evaluated the role of CD8 ϩ lymphocytes and, thereby, CD8 ϩ CTL in mediating protection against acute superinfection conferred by inoculation with live attenuated SIV.…”