title: Mechanisms of protection induced by attenuated simian immunodeficiency virus.
abstract: 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.
authors.affiliation: 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
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Stebbings
authors.forename: Neil M
authors.initials: NM
authors.lastname: Almond
authors.forename: E Jim
authors.initials: EJ
authors.lastname: Stott
authors.forename: Neil
authors.initials: N
authors.lastname: Berry
authors.forename: Alison M
authors.initials: AM
authors.lastname: Wade-Evans
authors.forename: Robin
authors.initials: R
authors.lastname: Hull
authors.forename: Jenny
authors.initials: J
authors.lastname: Lines
authors.forename: Peter
authors.initials: P
authors.lastname: Silvera
authors.forename: Rebecca
authors.initials: R
authors.lastname: Sangster
authors.forename: Terry
authors.initials: T
authors.lastname: Corcoran
authors.forename: Jane
authors.initials: J
authors.lastname: Rose
authors.forename: K Barry
authors.initials: KB
authors.lastname: Walker
mesh_terms: 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*
chemical_list: D007376:Interleukin-2; D018449:SAIDS Vaccines; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic; D015847:Interleukin-4; D007371:Interferon-gamma