Mechanisms of protection induced by attenuated simian immunodeficiency virus.
To determine whether attenuated simian immunodeficiency virus (SIV) vaccines confer protection against superinfection via secondary cellular immune responses, we searched for markers of immune activation following rechallenge. Productive infection with either attenuated SIVmacC8 or wild-type SIVmacJ5 resulted in a transient increase in T-lymphocyte CD25 and Mafa-DR expression. A pronounced increase in the frequency of FAS+ CD8+ lymphocytes was observed following SIVmacJ5 infection only. A transient increase in lymphocytes positive for intracellular IFN-gamma and IL-4 was observed following primary infection with either virus. In contrast, lymphocytes positive for intracellular IL-2 were reduced. Following SIVmacJ5 challenge of SIVmacC8-infected vaccinees, no evidence of detectable superinfection was obtained. Rechallenge of vaccinees did not alter the frequency of activated peripheral T-lymphocytes, perturb cytokine profiles, or generate an anamnestic antibody response. These data do not support the hypothesis that protection conferred by live attenuated SIV is mediated by the induction of vigorous T-cell responses upon rechallenge.
Stebbings
Richard J
RJ
Division of Immunobiology, Division of Retrovirology, National Institute for Biological Standards and Control, Blanche Lane, South Mimms, Potters Bar, Hertfordshire, United Kingdom. rstebbings@nibsc.ac.uk
Almond
Neil M
NM
Stott
E Jim
EJ
Berry
Neil
N
Wade-Evans
Alison M
AM
Hull
Robin
R
Lines
Jenny
J
Silvera
Peter
P
Sangster
Rebecca
R
Corcoran
Terry
T
Rose
Jane
J
Walker
K Barry
KB
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D007376:Interleukin-2 / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000096:biosynthesis*; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology / Q000821:virology; D008252:Macaca fascicularis; D008297:Male; D018449:SAIDS Vaccines / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology; D014613:Vaccines, Attenuated / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology*
D007376:Interleukin-2; D018449:SAIDS Vaccines; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic; D015847:Interleukin-4; D007371:Interferon-gamma