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

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

doi:10.1038/nm.4105

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

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

Research output: Contribution to journal › Article › peer-review

167 Scopus citations

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.

Original language	English (US)
Pages (from-to)	762-70
Number of pages	9
Journal	Nature Medicine
Volume	22
Issue number	7
DOIs	https://doi.org/10.1038/nm.4105
State	Published - Jul 2016
Externally published	Yes

Keywords

Adaptive Immunity/immunology
Adjuvants, Immunologic/therapeutic use
Alum Compounds/therapeutic use
Animals
Immunity, Innate/immunology
Immunity, Mucosal
Immunogenicity, Vaccine
Immunoglobulin G/immunology
Interleukin-17/immunology
Lymphocytes
Macaca mulatta
Membrane Glycoproteins/immunology
Random Allocation
SAIDS Vaccines/therapeutic use
Signal Transduction
Simian Acquired Immunodeficiency Syndrome/immunology
Simian Immunodeficiency Virus/immunology
Transcriptome
Viral Envelope Proteins/immunology
Viral Vaccines/therapeutic use
ras Proteins/immunology

PubMed: MeSH publication types

Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Intramural
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, N.I.H., Extramural

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/nm.4105

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Vaccari, M., Gordon, S. N., Fourati, S., Schifanella, L., Liyanage, N. P. M., Cameron, M., Keele, B. F., Shen, X., Tomaras, G. D., Billings, E., Rao, M., Chung, A. W., Dowell, K. G., Bailey-Kellogg, C., Brown, E. P., Ackerman, M. E., Vargas-Inchaustegui, D. A., Whitney, S., Doster, M. N., ... Franchini, G. (2016). Adjuvant-dependent innate and adaptive immune signatures of risk of SIVmac251 acquisition. Nature Medicine, 22(7), 762-70. https://doi.org/10.1038/nm.4105

Vaccari, M, Gordon, SN, Fourati, S, Schifanella, L, Liyanage, NPM, Cameron, M, Keele, BF, Shen, X, Tomaras, GD, Billings, E, Rao, M, Chung, AW, Dowell, KG, Bailey-Kellogg, C, Brown, EP, Ackerman, ME, Vargas-Inchaustegui, DA, Whitney, S, Doster, MN, Binello, N, Pegu, P, Montefiori, DC, Foulds, K, Quinn, DS, Donaldson, M, Liang, F, Loré, K, Roederer, M, Koup, RA, McDermott, A, Ma, Z-M, Miller, CJ, Phan, TB, Forthal, DN, Blackburn, M, Caccuri, F, Bissa, M, Ferrari, G, Kalyanaraman, V, Ferrari, MG, Thompson, D, Robert-Guroff, M, Ratto-Kim, S, Kim, JH, Michael, NL, Phogat, S, Barnett, SW, Tartaglia, J, Venzon, D, Stablein, DM, Alter, G, Sekaly, R-P & Franchini, G 2016, 'Adjuvant-dependent innate and adaptive immune signatures of risk of SIVmac251 acquisition', Nature Medicine, vol. 22, no. 7, pp. 762-70. https://doi.org/10.1038/nm.4105

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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.",

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

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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, DeVon

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

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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.

KW - Adaptive Immunity/immunology

KW - Adjuvants, Immunologic/therapeutic use

KW - Alum Compounds/therapeutic use

KW - Animals

KW - Immunity, Innate/immunology

KW - Immunity, Mucosal

KW - Immunogenicity, Vaccine

KW - Immunoglobulin G/immunology

KW - Interleukin-17/immunology

KW - Lymphocytes

KW - Macaca mulatta

KW - Membrane Glycoproteins/immunology

KW - Random Allocation

KW - SAIDS Vaccines/therapeutic use

KW - Signal Transduction

KW - Simian Acquired Immunodeficiency Syndrome/immunology

KW - Simian Immunodeficiency Virus/immunology

KW - Transcriptome

KW - Viral Envelope Proteins/immunology

KW - Viral Vaccines/therapeutic use

KW - ras Proteins/immunology

U2 - 10.1038/nm.4105

DO - 10.1038/nm.4105

M3 - Article

C2 - 27239761

SN - 1078-8956

VL - 22

SP - 762

EP - 770

JO - Nature Medicine

JF - Nature Medicine

IS - 7

ER -

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

Abstract

Keywords

PubMed: MeSH publication types

UN SDGs

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