Presence of circulating CTL induced by infection with wild‐type or attenuated SIV and their correlation with protection from pathogenic SHIV challenge

Abstract

The aim of this study was to evaluate the role of CTLs in the protection from challenge with pathogenic SHIV in macaques vaccinated with attenuated virus. More specifically, we have analyzed the CTL response in cynomolgus macaques vaccinated/infected with the attenuated SIVmacC8 or the wild-type SIVmacJ5 and correlated these responses to the protection from SHIV89.6P challenge. SIVmacC8-vaccinated monkeys demonstrated a broader CTL response than the SIVmacJ5-infected animals. Nevertheless, CTL against some proteins in SIVmacC8-vaccinated monkeys became progressively more difficult to detect through the day of challenge. In regards to protection from superinfection with SHIV89.6P, neither the presence of circulating CTL nor the CTL precursor frequency against any of the tested proteins correlated with the outcome of the challenge when SIVmacJ5- and SIVmacC8-infected animals were analyzed together. By analyzing the SIVmacC8-vaccinated animals separately, only the protected animal had detectable CTL precursors with moderate frequencies against all three tested proteins at the day of challenge.

Brain Microbial Populations in HIV/AIDS: α-Proteobacteria Predominate Independent of Host Immune Status

“…In addition, cerebral tissues were harvested from feline immunodeficiency virus-infected cats (12 weeks old) [44] and RAG1 −/− mice (>52 weeks of age) [47], housed under SPF conditions, from which RNA was prepared as described above. Brain tissues from simian (SIV; n = 10) [48] or simian-human immunodeficiency virus-infected (SHIV; n = 3) [49] or FIV-challenged adult cynomolgus macaques (n = 2) [50] were analyzed by initial preparation of RNA followed by RT-PCR amplification of cDNA and sequencing.…”

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

“…In addition, an inverse correlation has been reported between the precursor frequency of SIV-specific CD8 ϩ CTL responses elicited by certain vaccine approaches and virus load following challenge (20,55). Although several groups have reported a correlation between SIV-specific CD8 ϩ CTL responses in live attenuated SIV vaccinees and protection against superinfection with wild-type SIV (24)(25)(26)56), other groups have failed to corroborate such observations and dispute a role for SIVspecific CD8 ϩ CTL in mediating protection (1,32,44,50,52).…”

“…Inoculation with live attenuated SIV generates significant SIV-specific CD8 ϩ CTL responses (16,25,32,56). The appearance of SIV-specific CD8 ϩ CTL responses during primary SIV infection coincides with clearance of plasma viremia and suppression of viral replication (41).…”

Immunization of Rhesus Macaques with a DNA Prime/Modified Vaccinia Virus Ankara Boost Regimen Induces Broad Simian Immunodeficiency Virus (SIV)-Specific T-Cell Responses and Reduces Initial Viral Replication but Does Not Prevent Disease Progression following Challenge with Pathogenic SIVmac239

“…Therefore, the use of attenuated retroviruses as an AIDS vaccine is controversial (66,84). So far, the mechanism of protection induced by attenuated viruses is still unknown (6,8,69,94,98). The degree of protection achieved with attenuated viruses is variable and depends on the degree of attenuation of the vaccine virus (44), the time point of challenge (25), and the challenge virus chosen (102); all of these factors make determining the mechanism of protection very difficult.…”