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: Yongjun Sui, Susan Gagnon, Amiran Dzutsev, Qing Zhu, Huifeng Yu, Alison Hogg, Yichuan Wang, Zheng Xia, Igor M Belyakov, David Venzon, Dennis Klinman, Warren Strober, Brian Kelsall, Genoveffa Franchini, Jay A Berzofsky
• Journal: Vaccine (Vaccine) Vol. 30 Issue 1 Pg. 59-68 (Dec 09 2011) ISSN: 1873-2518 [Electronic] Netherlands
• PMID: 22041305 (Publication Type: Journal Article, Research Support, N.I.H., Intramural)
• Copyright: Published by Elsevier Ltd.

Chemical References

• Adjuvants, Immunologic
• Antigens, Viral
• Interleukin-15
• SAIDS Vaccines
• Toll-Like Receptors

Topics

• Adjuvants, Immunologic (metabolism)
• Administration, Mucosal
• Animals
• Antigens, Viral (immunology)
• CD4-Positive T-Lymphocytes (immunology)
• CD8-Positive T-Lymphocytes (immunology)
• Gastrointestinal Tract (immunology)
• Immunologic Memory
• Interleukin-15 (metabolism)
• Macaca mulatta
• SAIDS Vaccines (administration & dosage, immunology)
• Toll-Like Receptors (agonists)