Impact of vaccine-induced mucosal high-avidity CD8+ CTLs in delay of AIDS viral dissemination from mucosa.
Natural HIV transmission occurs through mucosa, but it is debated whether mucosal cytotoxic T lymphocytes (CTLs) can prevent or reduce dissemination from the initial mucosal site to the systemic circulation. Also, the role of CTL avidity in mucosal AIDS viral transmission is unknown. To address these questions, we used delay in acute-phase peak viremia after intrarectal challenge as an indicator of systemic dissemination. We found that a peptide-prime/poxviral boost vaccine inducing high levels of high-avidity mucosal CTLs can have an impact on dissemination of intrarectally administered pathogenic SHIV-ku2 in macaques and that such protection correlates better with mucosal than with systemic CTLs and particularly with levels of high-avidity mucosal CTLs.
Belyakov
Igor M
IM
Vaccine Branch, National Cancer Institute, Bethesda, MD 20892, USA. belyakov@mail.nih.gov
Kuznetsov
Vladimir A
VA
Kelsall
Brian
B
Klinman
Dennis
D
Moniuszko
Marcin
M
Lemon
Michael
M
Markham
Phillip D
PD
Pal
Ranajit
R
Clements
John D
JD
Lewis
Mark G
MG
Strober
Warren
W
Franchini
Genoveffa
G
Berzofsky
Jay A
JA
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000628:therapy / Q000635:transmission; D000285:Administration, Rectal; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D018928:Immunity, Mucosal / Q000276:immunology*; D007413:Intestinal Mucosa / Q000276:immunology / Q000821:virology; D008253:Macaca mulatta; D011212:Poxviridae / Q000235:genetics / Q000276:immunology; D014611:Vaccination / Q000379:methods; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology*
D016915:AIDS Vaccines; D022223:Vaccines, Subunit