Live attenuated simian immunodeficiency virus prevents super-infection by cloned SIVmac251 in cynomolgus monkeys.

Abstract

The ability of a live attenuated simian immunodeficiency virus (SIV) to protect against challenge with cloned SIVmac251/BK28 was evaluated in four cynomolgus macaques. The intravenous infection of the C8 variant of the SIVmac251/32H virus, carrying an in-frame 12 bp deletion in the nef gene, did not affect the CD4 M and CD8 M cell counts, and a persistent infection associated with an extremely low virus burden in peripheral blood mononuclear cells (PBMCs) was established. After 40 weeks, these monkeys were challenged intravenously with a 50 MID 50 dose of SIVmac251/BK28 virus grown on macaque cells. Four naive monkeys were infected as controls. Monkeys were monitored for 62 weeks following challenge. Attempts to rescue virus from either PBMCs or bone marrow from the C8-vaccinated monkeys were unsuccessful, but in two cases virus was re-isolated from lymph node cells. The

Persistence of Pathogenic Challenge Virus in Macaques Protected by Simian Immunodeficiency Virus SIVmacΔ nef

“…Currently, the most successful vaccines tested in the macaque model use a live attenuated SIV. The first demonstration of protection provided by an attenuated virus against challenge with a pathogenic virus (15) has been confirmed and extended by many authors (3,14,47,63,67,71). Protection is inversely correlated with the level of attenuation of the vaccine virus and requires several months to establish (39,71).…”

Long-term protection against SHIV89.6P replication in HIV-1 Tat vaccinated cynomolgus monkeys

“…Hybridization was performed according to established procedures [46] utilizing the FORN1/REVN1 PCR product as probe.…”

Extralymphoid CD8 + T Cells Resident in Tissue from Simian Immunodeficiency Virus SIVmac239Δnef-Vaccinated Macaques Suppress SIVmac239 Replication Ex Vivo

“…Macaques infected with live-attenuated SIV, like SIVmac239⌬nef, exhibit robust protection from pathogenic SIV infection (8,10,20,25,29,35,40,44,49,53). While previous studies have included considerable heterogeneity in the strain of attenuated SIV, challenge strain, and macaque species used, they demonstrate collectively the broad spectrum of attenuated SIVs that effectively protect macaques against pathogenic challenge.…”