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

2016; Nature Portfolio; Volume: 22; Issue: 7 Linguagem: Inglês

10.1038/nm.4105

1546-170X

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

Immunotherapy and Immune Responses

Vaccari et al. report that SIV vaccines formulated with two different adjuvants elicit distinct immune responses and effects on SIV acquisition in rhesus macaques. 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.