Adjuvant-dependent innate and adaptive immune signatures of risk of SIVmac251 acquisition

Monica Vaccari, Shari N. Gordon, Slim Fourati, Luca Schifanella, Namal P M Liyanage, Mark Cameron, Brandon F. Keele, Xiaoying Shen, Georgia D. Tomaras, Erik Billings, Mangala Rao, Amy W. Chung, Karen G. Dowell, Chris Bailey-Kellogg, Eric P. Brown, Margaret E. Ackerman, Diego A. Vargas-Inchaustegui, Stephen Whitney, Melvin N. Doster, Nicolo BinelloPoonam Pegu, David C. Montefiori, Kathryn Foulds, David S. Quinn, Mitzi Donaldson, Frank Liang, Karin Loré, Mario Roederer, Richard A. Koup, Adrian McDermott, Zhong Min Ma, Chris J Miller, Tran B. Phan, Donald N. Forthal, Matthew Blackburn, Francesca Caccuri, Massimiliano Bissa, Guido Ferrari, Vaniambadi Kalyanaraman, Maria G. Ferrari, De Von Thompson, Marjorie Robert-Guroff, Silvia Ratto-Kim, Jerome H. Kim, Nelson L. Michael, Sanjay Phogat, Susan W. Barnett, Jim Tartaglia, David Venzon, Donald M. Stablein, Galit Alter, Rafick Pierre Sekaly, Genoveffa Franchini

Research output: Contribution to journalArticlepeer-review

101 Scopus citations

Abstract

A recombinant vaccine containing Aventis Pasteur's canarypox vector (ALVAC)-HIV and gp120 alum decreased the risk of HIV acquisition in the RV144 vaccine trial. The substitution of alum with the more immunogenic MF59 adjuvant is under consideration for the next efficacy human trial. We found here that an ALVAC-simian immunodeficiency virus (SIV) and gp120 alum (ALVAC-SIV + gp120) equivalent vaccine, but not an ALVAC-SIV + gp120 MF59 vaccine, was efficacious in delaying the onset of SIVmac251 in rhesus macaques, despite the higher immunogenicity of the latter adjuvant. Vaccine efficacy was associated with alum-induced, but not with MF59-induced, envelope (Env)-dependent mucosal innate lymphoid cells (ILCs) that produce interleukin (IL)-17, as well as with mucosal IgG to the gp120 variable region 2 (V2) and the expression of 12 genes, ten of which are part of the RAS pathway. The association between RAS activation and vaccine efficacy was also observed in an independent efficacious SIV-vaccine approach. Whether RAS activation, mucosal ILCs and antibodies to V2 are also important hallmarks of HIV-vaccine efficacy in humans will require further studies.

Original languageEnglish (US)
Pages (from-to)762-770
Number of pages9
JournalNature Medicine
Volume22
Issue number7
DOIs
StatePublished - Jul 1 2016

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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