title: Lymph node T cell responses predict the efficacy of live attenuated SIV vaccines.
abstract: Live attenuated simian immunodeficiency virus (SIV) vaccines (LAVs) remain the most efficacious of all vaccines in nonhuman primate models of HIV and AIDS, yet the basis of their robust protection remains poorly understood. Here we show that the degree of LAV-mediated protection against intravenous wild-type SIVmac239 challenge strongly correlates with the magnitude and function of SIV-specific, effector-differentiated T cells in the lymph node but not with the responses of such T cells in the blood or with other cellular, humoral and innate immune parameters. We found that maintenance of protective T cell responses is associated with persistent LAV replication in the lymph node, which occurs almost exclusively in follicular helper T cells. Thus, effective LAVs maintain lymphoid tissue-based, effector-differentiated, SIV-specific T cells that intercept and suppress early wild-type SIV amplification and, if present in sufficient frequencies, can completely control and perhaps clear infection, an observation that provides a rationale for the development of safe, persistent vectors that can elicit and maintain such responses.
authors.affiliation: Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR, USA.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Fukazawa
authors.forename: Haesun
authors.initials: H
authors.lastname: Park
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Cameron
authors.forename: Francois
authors.initials: F
authors.lastname: Lefebvre
authors.forename: Richard
authors.initials: R
authors.lastname: Lum
authors.forename: Noel
authors.initials: N
authors.lastname: Coombes
authors.forename: Eisa
authors.initials: E
authors.lastname: Mahyari
authors.forename: Shoko I
authors.initials: SI
authors.lastname: Hagen
authors.forename: Jin Young
authors.initials: JY
authors.lastname: Bae
authors.forename: Marcelo Delos
authors.initials: MD
authors.lastname: Reyes
authors.forename: Tonya
authors.initials: T
authors.lastname: Swanson
authors.forename: Alfred W
authors.initials: AW
authors.lastname: Legasse
authors.forename: Andrew
authors.initials: A
authors.lastname: Sylwester
authors.forename: Scott G
authors.initials: SG
authors.lastname: Hansen
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Smith
authors.forename: Petra
authors.initials: P
authors.lastname: Stafova
authors.forename: Rebecca
authors.initials: R
authors.lastname: Shoemaker
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.forename: Kelli
authors.initials: K
authors.lastname: Oswald
authors.forename: Michael K
authors.initials: MK
authors.lastname: Axthelm
authors.forename: Adrian
authors.initials: A
authors.lastname: McDermott
authors.forename: Guido
authors.initials: G
authors.lastname: Ferrari
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.forename: Paul T
authors.initials: PT
authors.lastname: Edlefsen
authors.forename: Michael
authors.initials: M
authors.lastname: Piatak
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Lifson
authors.forename: Rafick P
authors.initials: RP
authors.lastname: Sékaly
authors.forename: Louis J
authors.initials: LJ
authors.lastname: Picker
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008253:Macaca mulatta / Q000276:immunology / Q000821:virology; D008297:Male; D018449:SAIDS Vaccines / Q000008:administration & dosage / Q000276:immunology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000276:immunology / Q000472:pathogenicity; D014018:Tissue Distribution; D014613:Vaccines, Attenuated / Q000276:immunology; D014779:Virus Replication / Q000235:genetics
chemical_list: D018449:SAIDS Vaccines; D014613:Vaccines, Attenuated