TY - JOUR
T1 - Adjuvant-dependent innate and adaptive immune signatures of risk of SIVmac251 acquisition
AU - Vaccari, Monica
AU - Gordon, Shari N.
AU - Fourati, Slim
AU - Schifanella, Luca
AU - Liyanage, Namal P.M.
AU - Cameron, Mark
AU - Keele, Brandon F.
AU - Shen, Xiaoying
AU - Tomaras, Georgia D.
AU - Billings, Erik
AU - Rao, Mangala
AU - Chung, Amy W.
AU - Dowell, Karen G.
AU - Bailey-Kellogg, Chris
AU - Brown, Eric P.
AU - Ackerman, Margaret E.
AU - Vargas-Inchaustegui, Diego A.
AU - Whitney, Stephen
AU - Doster, Melvin N.
AU - Binello, Nicolo
AU - Pegu, Poonam
AU - Montefiori, David C.
AU - Foulds, Kathryn
AU - Quinn, David S.
AU - Donaldson, Mitzi
AU - Liang, Frank
AU - Loré, Karin
AU - Roederer, Mario
AU - Koup, Richard A.
AU - McDermott, Adrian
AU - Ma, Zhong Min
AU - Miller, Christopher J.
AU - Phan, Tran B.
AU - Forthal, Donald N.
AU - Blackburn, Matthew
AU - Caccuri, Francesca
AU - Bissa, Massimiliano
AU - Ferrari, Guido
AU - Kalyanaraman, Vaniambadi
AU - Ferrari, Maria G.
AU - Thompson, De Von
AU - Robert-Guroff, Marjorie
AU - Ratto-Kim, Silvia
AU - Kim, Jerome H.
AU - Michael, Nelson L.
AU - Phogat, Sanjay
AU - Barnett, Susan W.
AU - Tartaglia, Jim
AU - Venzon, David
AU - Stablein, Donald M.
AU - Alter, Galit
AU - Sekaly, Rafick Pierre
AU - Franchini, Genoveffa
N1 - Funding Information:
This work was supported by the intramural US National Cancer Institute (NCI) program and the extramural US National Institute of Allergy and Infectious Diseases (NIAID) program, together with the US Army Medical Research and Material Command (USAMRMC) (W81XWH-07-2-0067), the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., the US Department of Defense, the Collaboration for AIDS Vaccine Discovery (CAVD) grants OPP1032325 and OPP1032817 from the Bill and Melinda Gates Foundation, and in part, with federal funds from the NCI, US National Institutes of Health (NIH), under contract no. HHSN261200800001E (to the whole team). We would like to acknowledge the following institutions for the grants supporting the authors: NIH primate grant HHSN27201100016C (D.M.); Center for AIDS Research grant AI064518 (G.F.); Bill and Melinda Gates' Foundation grant OPP111572 (M.E.A., C.B.K., E.F.B., K.G.D.); NIH/NIAID grant 5R01AI102691 (M.E.A, E.F.B.); Intramural Research Program of the Vaccine Research Center, NIAID, NIH, and CAVD from the Bill and Melinda Gates Foundation grants OPP1032325 (R.A.K.), R01 AI118581 and R01 AI102715 (D.F.).
Funding Information:
We would like to thank T. Nolan and D. Abram for their editorial assistance, N. Miller and A. Shultz for their help in the study design, and J. Warren for support with systems biology and several antibody assays under Simian Vaccine Evaluation Unit (SVEU) contract number HHSN266200600005C, awarded to Advanced BioScience Laboratories, Inc. (ABL). This work was supported by the intramural US National Cancer Institute (NCI) program and the extramural US National Institute of Allergy and Infectious Diseases (NIAID) program, together with the US Army Medical Research and Material Command (USAMRMC) (W81XWH-07-2-0067), the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., the US Department of Defense, the Collaboration for AIDS Vaccine Discovery (CAVD) grants OPP1032325 and OPP1032817 from the Bill and Melinda Gates Foundation, and in part, with federal funds from the NCI, US National Institutes of Health (NIH), under contract no. HHSN261200800001E (to the whole team). We would like to acknowledge the following institutions for the grants supporting the authors: NIH primate grant HHSN27201100016C (D.M.); Center for AIDS Research grant AI064518 (G.F.); Bill and Melinda Gates’ Foundation grant OPP111572 (M.E.A., C.B.K., E.F.B., K.G.D.); NIH/NIAID grant 5R01AI102691 (M.E.A, E.F.B.); Intramural Research Program of the Vaccine Research Center, NIAID, NIH, and CAVD from the Bill and Melinda Gates Foundation grants OPP1032325 (R.A.K.), R01 AI118581 and R01 AI102715 (D.F.). The views expressed are those of the authors and should not be construed to represent the positions of the US Army, the Department of Defense or the Department of Health and Human Services. Mention of trade names, commercial products, or organizations do not imply endorsement by the US Government. The following reagent was obtained through the NIH AIDS Reagent Program, Division of AIDS, NIAID, NIH: CEM.NKR CCR5+by P. Creswell. The anti-α4β7 in APC was kindly provided by A. A. Ansari (cat. #11718, 1:50 dilution) through the NIH AIDS Reagent Program, Division of AIDS, NIAID.
Publisher Copyright:
© 2016 Nature America, Inc. All rights reserved.
PY - 2016/7/1
Y1 - 2016/7/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84976622734&partnerID=8YFLogxK
U2 - 10.1038/nm.4105
DO - 10.1038/nm.4105
M3 - Article
C2 - 27239761
AN - SCOPUS:84976622734
SN - 1078-8956
VL - 22
SP - 762
EP - 770
JO - Nature Medicine
JF - Nature Medicine
IS - 7
ER -