Mechanisms of protection induced by attenuated simian immunodeficiency virus. I. Protection cannot be transferred with immune serum.

Abstract

To evaluate its role in protection, immune serum was collected from four macaques which were chronically infected with live attenuated simian immunodeficiency virus (SIVmacC8) and had resisted challenge with wild-type SIVmacJ5. The immune serum was transferred to two naı$ ve cynomolgus macaques by intraperitoneal injection (11 ml/kg). Four control macaques received an intraperitoneal injection of normal saline. One day later, all macaques were challenged with 10 MID 50 of the J5M challenge stock of SIV. After challenge, all macaques became infected as determined by virus co-culture and diagnostic PCR. Virus loads in PBMC at 2 weeks post-challenge were indistinguishable between the two groups of macaques. Thus, the failure of passive immunization to transfer protection indicates that serum components alone are not sufficient to mediate the potent protection obtained using live attenuated vaccines. This is the first time that serum has been transferred from animals known to be protected against superinfection.

Resistance to superinfection by a vigorously replicating, uncloned stock of simian immunodeficiency virus (SIVmac251) stimulates replication of a live attenuated virus vaccine (SIVmacC8)

“…Our previous reports have not identified a central role for adaptive immunity in the protection conferred by SIVmacC8 (Stebbings et al, 2005;Almond et al, 1997). In this study, neutralizing antibody responses were poor and did not correlate with protection.…”

“…The ability for live attenuated SIV to protect against wild-type virus challenge and the parameters governing this protection are of crucial importance in unravelling which responses might be required to develop a successful AIDS vaccine. A role for antiviral antibodies is unlikely, since vaccination with live attenuated SIV confers protection against challenge with chimeric simian-human immunodeficiency viruses (SHIVs) expressing human immunodeficiency virus (HIV)-1 envelope which is not cross-neutralized in vitro (Bogers et al, 1995;Dunn et al, 1997;Wyand et al, 1999) and since transfer of immune serum has not transferred protection (Almond et al, 1997). Live attenuated SIV elicits potent, long-lived CD4 + responses (Gauduin et al, 1999;Sarkar et al, 2002) and CD8…”

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

“…This study is part of a series that has characterized the early protection against superinfection conferred by inoculation with live nef-attenuated SIVmacC8 (3,5,48,(50)(51)(52). Previously, we showed that protection against acute superinfection with pathogenic, wild-type SIVmacJ5 can be obtained within 21 days of inoculation with live attenuated SIVmacC8, at a time when neutralizing antibodies were not present and limited CD8 ϩ T lymphocyte responses were detected (51).…”

Killing Kinetics of Simian Immunodeficiency Virus-Specific CD8+ T Cells: Implications for HIV Vaccine Strategies

“…Protection afforded by LAV vaccines using SIV could not be transferred with passive Abs (25). Effective T cell immune responses may be preprimed to kill infected cells and control viremia in animals inoculated with live-attenuated SIV vaccines.…”