Innate anti-viral immunity is associated with the protection elicited by the simian immunodeficiency virus (SIV) live attenuated virus vaccine in cynomolgus monkeys.
BACKGROUND
The Delta-nef live attenuated virus vaccine approach offered in the SIV-macaque model the opportunity to identify humoral and cell-mediated immune responses associated with protection against viral infections. In addition, soluble factors different from those related to specific immune responses appear to correlate with the establishment and maintenance of the protective status.


METHODS
Investigated were: 1) the ability of CD8+ T cells from cynomolgus monkeys vaccinated with SIV Delta-nef and long-term protected against sequential SIVs and SHIV challenges to inhibit in vitro SHIV replication in an acute infection cell system, 2) the ability of cell-free supernatants from CD8+ T cell cultures to inhibit replication of HIV in chronically infected cells, and 3) whether the antiviral activity of CD8+ T cells correlated with IFNgamma production.


RESULTS
Soluble factor(s) secreted by CD8+ T cells from Delta-nef vaccinated monkeys significantly inhibited SHIV replication in an autologous cell system. This effect was not dependent on beta-chemokine secretion and correlated with an increased IFNgamma production. In addition, since supernatants from CD8+ T cells inhibited HIV production in chronically infected monocytic cells, the suppressive activity was not related to the viral strain.


CONCLUSIONS
Vaccination with the live attenuated virus induces both a CD8+ T cell-dependent antiviral activity and IFNgamma responses potentially responsible for the protection from challenge with heterologous highly pathogenic SHIV89.6P. It is conceivable that boosting the "natural" along with the antigen-specific immunity is a desirable outcome to improve the protective efficacy of any vaccine approach.
Goletti
Delia
D
2nd Division of the Health Department, National Institute of Infectious Disease, L. Spallanzani, Rome, Italy.
Macchia
Iole
I
Leone
Pasqualina
P
Pace
Monica
M
Sernicola
Leonardo
L
Pavone-Cossut
Maria Rosaria
MR
Maggiorella
Maria Teresa
MT
Cafaro
Aurelio
A
Ensoli
Barbara
B
Titti
Fausto
F
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002474:Cell-Free System; D002478:Cells, Cultured; D015693:Gene Products, nef / Q000235:genetics / Q000276:immunology; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000096:biosynthesis; D008252:Macaca fascicularis; D008297:Male; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity / Q000502:physiology; D013997:Time Factors; D014611:Vaccination; D014613:Vaccines, Attenuated / Q000008:administration & dosage*; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology*; D014779:Virus Replication / Q000276:immunology
D015693:Gene Products, nef; D014613:Vaccines, Attenuated; D014765:Viral Vaccines; D007371:Interferon-gamma