Early suppression of SIV replication by CD8+ nef-specific cytotoxic T cells in vaccinated macaques

Abstract

In order to develop a successful subunit vaccine against infection with the human immunodeficiency virus (HIV), protective immune effector functions must be identified. Until now, there has been only indirect evidence that HIV-specific cytotoxic T lymphocytes (CTLs) fulfill this role. Using the macaque simian immunodeficiency virus (SIV) model, the protective potential of nef-specific CTLs, stimulated by vaccination, was examined in animals challenged with a high intravenous dose of the pathogenic simian immunodeficiency virus, SIVmac251(32H)(pJ5). An inverse correlation was found between the vaccine-induced nef-specific CTL precursor frequency and virus load measured after challenge. In addition, the early decline in viraemia, observed in both vaccinated and unvaccinated control animals was associated with the development of virus-specific CTL activity and not with the presence of virus-specific neutralizing antibodies. The results imply that vaccines that stimulate strong CTL responses could protect against HIV infection.

Engineering RENTA, a DNA prime-MVA boost HIV vaccine tailored for Eastern and Central Africa

“…[24][25][26][27] In vivo, vaccineinduced CTL against early proteins provided a degree of protection against pathogenic virus challenges. [28][29][30] However, the protective role of Tat alone has been controversial. Despite initial successful reports, 31,32 subsequent studies failed to demonstrate protective efficacy of Tat-specific CTL only.…”

In vivo resistance to simian immunodeficiency virus superinfection depends on attenuated virus dose.

“…Ficoll-Hypaque isolated PBMC were stimulated in vitro with autologous SIV-infected PHA blasts (Gallimore et al, 1995). One-fifth of the isolated PBMC were prepared for use as stimulator cells while the remaining cells were maintained overnight at 37 mC.…”

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

“…Furthermore, the importance of CD8 ϩ lymphocytes for control of pathogenic or attenuated SIV infection has been demonstrated in several studies that report a dramatic rise in plasma viremia following anti-CD8 monoclonal antibody (MAb) treatment to deplete CD8 ϩ CTL, with control of virus replication being temporally associated with recovery of CD8 ϩ lymphocytes (23,28,30,41). 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).…”