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

作者信息

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

机构信息

Animal Models and Vaccine Section, National Cancer Institute, Bethesda, Maryland, USA.

Department of Pathology, Case Western Reserve, Cleveland, Ohio, USA.

出版信息

Nat Med. 2016 Jul;22(7):762-70. doi: 10.1038/nm.4105. Epub 2016 May 30.

DOI:10.1038/nm.4105
PMID:27239761
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5916782/
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.

摘要

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本文引用的文献

[1]
Plasmacytoid dendritic cells promote HIV-1-induced group 3 innate lymphoid cell depletion.

J Clin Invest. 2015-9

[2]
Multiple low-dose challenges in a rhesus macaque AIDS vaccine trial result in an evolving host response that affects protective outcome.

Clin Vaccine Immunol. 2014-12

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AIDS. 2014-11-13

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MAbs. 2014

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PLoS One. 2014-4-11

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Antiretroviral therapy partly reverses the systemic and mucosal distribution of NK cell subsets that is altered by SIVmac₂₅₁ infection of macaques.

Virology. 2014-1-21

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Plasma IgG to linear epitopes in the V2 and V3 regions of HIV-1 gp120 correlate with a reduced risk of infection in the RV144 vaccine efficacy trial.

PLoS One. 2013-9-26

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Expert Rev Vaccines. 2013-7

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J Virol. 2013-7-10

[10]
CD160 activation by herpesvirus entry mediator augments inflammatory cytokine production and cytolytic function by NK cells.

J Immunol. 2013-6-12

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