Adjuvant-dependent innate and adaptive immune signatures of risk of SIVmac251 acquisition.
Monica VaccariShari N GordonSlim FouratiLuca SchifanellaNamal P M LiyanageMark CameronBrandon F KeeleXiaoying ShenGeorgia D TomarasErik BillingsMangala RaoAmy W ChungKaren G DowellChris Bailey-KelloggEric P BrownMargaret E AckermanDiego A Vargas-InchausteguiStephen WhitneyMelvin N DosterNicolo BinelloPoonam PeguDavid C MontefioriKathryn FouldsDavid S QuinnMitzi DonaldsonFrank LiangKarin LoréMario RoedererRichard A KoupAdrian McDermottZhong-Min MaChristopher J MillerTran B PhanDonald N ForthalMatthew BlackburnFrancesca CaccuriMassimiliano BissaGuido FerrariVaniambadi KalyanaramanMaria G FerrariDeVon ThompsonMarjorie Robert-GuroffSilvia Ratto-KimJerome H KimNelson L MichaelSanjay PhogatSusan W BarnettJim TartagliaDavid J VenzonDonald M StableinGalit AlterRafick-Pierre SekalyGenoveffa FranchiniPublished in: Nature medicine (2016)
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.
Keyphrases
- antiretroviral therapy
- hiv positive
- hiv infected
- early stage
- human immunodeficiency virus
- hepatitis c virus
- hiv testing
- clinical trial
- hiv aids
- mycobacterium tuberculosis
- randomized controlled trial
- study protocol
- endothelial cells
- high glucose
- men who have sex with men
- genome wide
- oxidative stress
- phase ii
- south africa
- cell proliferation
- gene expression
- signaling pathway
- wild type
- diabetic rats
- double blind
- binding protein