title: Vaccine-induced T cells provide partial protection against high-dose rectal SIVmac239 challenge of rhesus macaques.
abstract: Despite enormous efforts by the scientific community, an effective HIV vaccine remains elusive. To further address to what degree T cells in absence of antibodies may protect against simian immunodeficiency virus (SIV) disease progression, rhesus macaques were vaccinated intramuscularly with a chimpanzee-derived Ad vector (AdC) serotype 6 and then boosted intramuscularly with a serologically distinct AdC vector of serotype 7 both expressing Gag of SIVmac239. Animals were subsequently boosted intramuscularly with a modified vaccinia Ankara (MVA) virus expressing Gag and Tat of the homologous SIV before mucosal challenge with a high dose of SIVmac239 given rectally. Whereas vaccinated animals showed only a modest reduction of viral loads, their overall survival was improved, in association with a substantial protection from the loss of CD4(+) T cells. In addition, the two vaccinated Mamu-A*01(+) macaques controlled viral loads to levels below detection within weeks after challenge. These data strongly suggest that T cells, while unable to affect SIV acquisition upon high-dose rectal infection, can reduce disease progression. Induction of potent T-cell responses should thus remain a component of our efforts to develop an efficacious vaccine to HIV-1.
authors.affiliation: The Wistar Institute, Philadelphia, PA, USA.
authors.forename: Marcio O
authors.initials: MO
authors.lastname: Lasaro
authors.forename: Larissa H
authors.initials: LH
authors.lastname: Haut
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Zhou
authors.forename: Zhiquan
authors.initials: Z
authors.lastname: Xiang
authors.forename: Dongming
authors.initials: D
authors.lastname: Zhou
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Wynetta
authors.initials: W
authors.lastname: Giles-Davis
authors.forename: Hua
authors.initials: H
authors.lastname: Li
authors.forename: Jessica C
authors.initials: JC
authors.lastname: Engram
authors.forename: Lauren J
authors.initials: LJ
authors.lastname: Dimenna
authors.forename: Ang
authors.initials: A
authors.lastname: Bian
authors.forename: Marina
authors.initials: M
authors.lastname: Sazanovich
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Parzych
authors.forename: Raj
authors.initials: R
authors.lastname: Kurupati
authors.forename: Juliana C
authors.initials: JC
authors.lastname: Small
authors.forename: Te-Lang
authors.initials: TL
authors.lastname: Wu
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Leskowitz
authors.forename: Nicole R
authors.initials: NR
authors.lastname: Klatt
authors.forename: Jason M
authors.initials: JM
authors.lastname: Brenchley
authors.forename: David A
authors.initials: DA
authors.lastname: Garber
authors.forename: Mark
authors.initials: M
authors.lastname: Lewis
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Ratcliffe
authors.forename: Michael R
authors.initials: MR
authors.lastname: Betts
authors.forename: Guido
authors.initials: G
authors.lastname: Silvestri
authors.forename: Hildegund C
authors.initials: HC
authors.lastname: Ertl
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D008253:Macaca mulatta / Q000276:immunology* / Q000821:virology*; D008297:Male; D018449:SAIDS Vaccines / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology* / Q000472:pathogenicity*
chemical_list: D018449:SAIDS Vaccines