| Literature DB >> 27239761 |
Monica Vaccari1, Shari N Gordon1, Slim Fourati2, Luca Schifanella1,3, Namal P M Liyanage1, Mark Cameron4, Brandon F Keele5, Xiaoying Shen6, Georgia D Tomaras6, Erik Billings7, Mangala Rao7, Amy W Chung8, Karen G Dowell9, Chris Bailey-Kellogg9, Eric P Brown10, Margaret E Ackerman10, Diego A Vargas-Inchaustegui11, Stephen Whitney12, Melvin N Doster1, Nicolo Binello1, Poonam Pegu1, David C Montefiori13, Kathryn Foulds14, David S Quinn14, Mitzi Donaldson14, Frank Liang15, Karin Loré15, Mario Roederer14, Richard A Koup14, Adrian McDermott14, Zhong-Min Ma16, Christopher J Miller16, Tran B Phan17, Donald N Forthal17, Matthew Blackburn1, Francesca Caccuri1, Massimiliano Bissa1, Guido Ferrari6, Vaniambadi Kalyanaraman12, Maria G Ferrari12, DeVon Thompson12, Marjorie Robert-Guroff11, Silvia Ratto-Kim7, Jerome H Kim7, Nelson L Michael7, Sanjay Phogat18, Susan W Barnett19, Jim Tartaglia18, David Venzon20, Donald M Stablein21, Galit Alter8, Rafick-Pierre Sekaly2, Genoveffa Franchini1.
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.Entities:
Mesh：
Substances：
Year: 2016 PMID： 27239761 PMCID： PMC5916782 DOI： 10.1038/nm.4105
Source DB: PubMed Journal: Nat Med ISSN： 1078-8956 Impact factor: 53.440