Early suppression of SIV replication by CD8+ nef-specific cytotoxic T cells in vaccinated macaques.
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.
Gallimore
A
A
Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK.
Cranage
M
M
Cook
N
N
Almond
N
N
Bootman
J
J
Rud
E
E
Silvera
P
P
Dennis
M
M
Corcoran
T
T
Stott
J
J
D000818:Animals; D002478:Cells, Cultured; D004279:DNA, Viral / Q000097:blood; D015683:Gene Products, gag / Q000097:blood; D015693:Gene Products, nef / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000821:virology; D008252:Macaca fascicularis; D016133:Polymerase Chain Reaction; D011533:Proviruses / Q000235:genetics; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000502:physiology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014611:Vaccination; D014614:Vaccines, Synthetic; D014765:Viral Vaccines / Q000276:immunology*; D014766:Viremia / Q000517:prevention & control; D014779:Virus Replication
D004279:DNA, Viral; C066594:Gag protein p27, Simian immunodeficiency virus; D015683:Gene Products, gag; D015693:Gene Products, nef; D014614:Vaccines, Synthetic; D014765:Viral Vaccines