title: TLR agonists and/or IL-15 adjuvanted mucosal SIV vaccine reduced gut CD4⁺ memory T cell loss in SIVmac251-challenged rhesus macaques.
abstract: Adjuvant plays an important role in increasing and directing vaccine-induced immune responses. In a previous study, we found that a mucosal SIV vaccine using a combination of IL-15 and TLR agonists as adjuvant mediated partial protection against SIVmac251 rectal challenge, whereas neither IL-15 nor TLR agonists alone as an adjuvant impacted the plasma viral loads. In this study, dissociation of CD4(+) T cell preservation with viral loads was observed in the animals vaccinated with adjuvants. Significantly higher levels of memory CD4(+) T cell numbers were preserved after SIVmac251 infection in the colons of the animals vaccinated with vaccine containing any of these adjuvants compared to no adjuvant. When we measured the viral-specific CD8(+) tetramer responses in the colon lamina propria, we found significantly higher levels of gag, tat, and pol epitope tetramer(+) T cell responses in these animals compared to ones without adjuvant, even if some of the animals had similarly high viral loads. Furthermore, this CD4(+) T preservation was positively correlated with increased levels of gag and Tat, but not pol tetramer(+) T cell responses, and inversely correlated with beta-chemokine expression. The pre-challenged APOBEC3G expression level, which has previously been shown inversely associated with viral loads, was further found positively correlated with CD4(+) T cell number preservation. Overall, these data highlight one unrecognized role of adjuvant in HIV vaccine development, and show that vaccines can produce a surprising discordance between CD4(+) T cell levels and SIV viral load.
authors: Vaccine Branch, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, United States. suiy@mail.nih.gov
authors: Yongjun
authors: Y
authors: Sui
authors: Susan
authors: S
authors: Gagnon
authors: Amiran
authors: A
authors: Dzutsev
authors: Qing
authors: Q
authors: Zhu
authors: Huifeng
authors: H
authors: Yu
authors: Alison
authors: A
authors: Hogg
authors: Yichuan
authors: Y
authors: Wang
authors: Zheng
authors: Z
authors: Xia
authors: Igor M
authors: IM
authors: Belyakov
authors: David
authors: D
authors: Venzon
authors: Dennis
authors: D
authors: Klinman
authors: Warren
authors: W
authors: Strober
authors: Brian
authors: B
authors: Kelsall
authors: Genoveffa
authors: G
authors: Franchini
authors: Jay A
authors: JA
authors: Berzofsky
mesh_terms: D000276:Adjuvants, Immunologic / Q000378:metabolism*; D058956:Administration, Mucosal; D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D041981:Gastrointestinal Tract / Q000276:immunology*; D007156:Immunologic Memory; D019409:Interleukin-15 / Q000378:metabolism*; D008253:Macaca mulatta; D018449:SAIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D051193:Toll-Like Receptors / Q000819:agonists*
chemical_list: D000276:Adjuvants, Immunologic; D000956:Antigens, Viral; D019409:Interleukin-15; D018449:SAIDS Vaccines; D051193:Toll-Like Receptors