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; De Von 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 SIV_mac251 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, De Von 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^*

^*Corresponding author for this work

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

173 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 SIV_mac251 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
Pages (from-to)	762-770
Number of pages	9
Journal	Nature Medicine
Volume	22
Issue number	7
DOIs	https://doi.org/10.1038/nm.4105
State	Published - 1 Jul 2016
Externally published	Yes

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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 SIV_mac251 acquisition. Nature Medicine, 22(7), 762-770. https://doi.org/10.1038/nm.4105

@article{34ca71883a78446f99530d870fa38d02,

title = "Adjuvant-dependent innate and adaptive immune signatures of risk of SIVmac251 acquisition",

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.",

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 Ma, {Zhong Min} 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 Thompson, {De Von} 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 Sekaly, {Rafick Pierre} and Genoveffa Franchini",

year = "2016",

month = jul,

day = "1",

doi = "10.1038/nm.4105",

language = "English",

volume = "22",

pages = "762--770",

journal = "Nature Medicine",

issn = "1078-8956",

number = "7",

}

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, ZM, Miller, CJ, Phan, TB, Forthal, DN, Blackburn, M, Caccuri, F, Bissa, M, Ferrari, G, Kalyanaraman, V, Ferrari, MG, Thompson, DV, Robert-Guroff, M, Ratto-Kim, S, Kim, JH, Michael, NL, Phogat, S, Barnett, SW, Tartaglia, J, Venzon, D, Stablein, DM, Alter, G, Sekaly, RP & Franchini, G 2016, 'Adjuvant-dependent innate and adaptive immune signatures of risk of SIV_mac251 acquisition', Nature Medicine, vol. 22, no. 7, pp. 762-770. https://doi.org/10.1038/nm.4105

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

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.

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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 -

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

Abstract

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Adjuvant-dependent innate and adaptive immune signatures of risk of SIV_mac251 acquisition