Therapeutic efficacy of an Ad26/MVA vaccine with SIV gp140 protein and vesatolimod in ART-suppressed rhesus macaques

John D. Ventura; Joseph P. Nkolola; Abishek Chandrashekar; Erica N. Borducchi; Jinyan Liu; Noe B. Mercado; David L. Hope; Victoria M. Giffin; Katherine McMahan; Romas Geleziunas; Jeffrey P. Murry; Yunling Yang; Mark G. Lewis; Maria G. Pau; Frank Wegmann; Hanneke Schuitemaker; Emily J. Fray; Mithra R. Kumar; Janet D. Siliciano; Robert F. Siliciano; Merlin L. Robb; Nelson L. Michael; Dan H. Barouch

doi:10.1038/s41541-022-00477-x

Therapeutic efficacy of an Ad26/MVA vaccine with SIV gp140 protein and vesatolimod in ART-suppressed rhesus macaques

John D. Ventura, Joseph P. Nkolola, Abishek Chandrashekar, Erica N. Borducchi, Jinyan Liu, Noe B. Mercado, David L. Hope, Victoria M. Giffin, Katherine McMahan, Romas Geleziunas, Jeffrey P. Murry, Yunling Yang, Mark G. Lewis, Maria G. Pau, Frank Wegmann, Hanneke Schuitemaker, Emily J. Fray, Mithra R. Kumar, Janet D. Siliciano, Robert F. SilicianoMerlin L. Robb, Nelson L. Michael, Dan H. Barouch^*

^*Corresponding author for this work

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

7 Scopus citations

Abstract

Developing an intervention that results in virologic control following discontinuation of antiretroviral therapy (ART) is a major objective of HIV-1 cure research. In this study, we investigated the therapeutic efficacy of a vaccine consisting of adenovirus serotype 26 (Ad26) and modified vaccinia Ankara (MVA) with or without an SIV Envelope (Env) gp140 protein with alum adjuvant in combination with the TLR7 agonist vesatolimod (GS-9620) in 36 ART-suppressed, SIVmac251-infected rhesus macaques. Ad26/MVA therapeutic vaccination led to robust humoral and cellular immune responses, and the Env protein boost increased antibody responses. Following discontinuation of ART, virologic control was observed in 5/12 animals in each vaccine group, compared with 0/12 animals in the sham control group. These data demonstrate therapeutic efficacy of Ad26/MVA vaccination with vesatolimod but no clear additional benefit of adding an Env protein boost. SIV-specific cellular immune responses correlated with virologic control. Our findings show partial efficacy of therapeutic vaccination following ART discontinuation in SIV-infected rhesus macaques.

Original language	English
Article number	53
Journal	npj Vaccines
Volume	7
Issue number	1
DOIs	https://doi.org/10.1038/s41541-022-00477-x
State	Published - Dec 2022
Externally published	Yes

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Ventura, J. D., Nkolola, J. P., Chandrashekar, A., Borducchi, E. N., Liu, J., Mercado, N. B., Hope, D. L., Giffin, V. M., McMahan, K., Geleziunas, R., Murry, J. P., Yang, Y., Lewis, M. G., Pau, M. G., Wegmann, F., Schuitemaker, H., Fray, E. J., Kumar, M. R., Siliciano, J. D., ... Barouch, D. H. (2022). Therapeutic efficacy of an Ad26/MVA vaccine with SIV gp140 protein and vesatolimod in ART-suppressed rhesus macaques. npj Vaccines, 7(1), Article 53. https://doi.org/10.1038/s41541-022-00477-x

@article{2b5f586517b74c76933d602ba56496fe,

title = "Therapeutic efficacy of an Ad26/MVA vaccine with SIV gp140 protein and vesatolimod in ART-suppressed rhesus macaques",

abstract = "Developing an intervention that results in virologic control following discontinuation of antiretroviral therapy (ART) is a major objective of HIV-1 cure research. In this study, we investigated the therapeutic efficacy of a vaccine consisting of adenovirus serotype 26 (Ad26) and modified vaccinia Ankara (MVA) with or without an SIV Envelope (Env) gp140 protein with alum adjuvant in combination with the TLR7 agonist vesatolimod (GS-9620) in 36 ART-suppressed, SIVmac251-infected rhesus macaques. Ad26/MVA therapeutic vaccination led to robust humoral and cellular immune responses, and the Env protein boost increased antibody responses. Following discontinuation of ART, virologic control was observed in 5/12 animals in each vaccine group, compared with 0/12 animals in the sham control group. These data demonstrate therapeutic efficacy of Ad26/MVA vaccination with vesatolimod but no clear additional benefit of adding an Env protein boost. SIV-specific cellular immune responses correlated with virologic control. Our findings show partial efficacy of therapeutic vaccination following ART discontinuation in SIV-infected rhesus macaques.",

author = "Ventura, {John D.} and Nkolola, {Joseph P.} and Abishek Chandrashekar and Borducchi, {Erica N.} and Jinyan Liu and Mercado, {Noe B.} and Hope, {David L.} and Giffin, {Victoria M.} and Katherine McMahan and Romas Geleziunas and Murry, {Jeffrey P.} and Yunling Yang and Lewis, {Mark G.} and Pau, {Maria G.} and Frank Wegmann and Hanneke Schuitemaker and Fray, {Emily J.} and Kumar, {Mithra R.} and Siliciano, {Janet D.} and Siliciano, {Robert F.} and Robb, {Merlin L.} and Michael, {Nelson L.} and Barouch, {Dan H.}",

note = "Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = dec,

doi = "10.1038/s41541-022-00477-x",

language = "English",

volume = "7",

journal = "npj Vaccines",

issn = "2059-0105",

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Ventura, JD, Nkolola, JP, Chandrashekar, A, Borducchi, EN, Liu, J, Mercado, NB, Hope, DL, Giffin, VM, McMahan, K, Geleziunas, R, Murry, JP, Yang, Y, Lewis, MG, Pau, MG, Wegmann, F, Schuitemaker, H, Fray, EJ, Kumar, MR, Siliciano, JD, Siliciano, RF, Robb, ML, Michael, NL & Barouch, DH 2022, 'Therapeutic efficacy of an Ad26/MVA vaccine with SIV gp140 protein and vesatolimod in ART-suppressed rhesus macaques', npj Vaccines, vol. 7, no. 1, 53. https://doi.org/10.1038/s41541-022-00477-x

TY - JOUR

T1 - Therapeutic efficacy of an Ad26/MVA vaccine with SIV gp140 protein and vesatolimod in ART-suppressed rhesus macaques

AU - Ventura, John D.

AU - Nkolola, Joseph P.

AU - Chandrashekar, Abishek

AU - Borducchi, Erica N.

AU - Liu, Jinyan

AU - Mercado, Noe B.

AU - Hope, David L.

AU - Giffin, Victoria M.

AU - McMahan, Katherine

AU - Geleziunas, Romas

AU - Murry, Jeffrey P.

AU - Yang, Yunling

AU - Lewis, Mark G.

AU - Pau, Maria G.

AU - Wegmann, Frank

AU - Schuitemaker, Hanneke

AU - Fray, Emily J.

AU - Kumar, Mithra R.

AU - Siliciano, Janet D.

AU - Siliciano, Robert F.

AU - Robb, Merlin L.

AU - Michael, Nelson L.

AU - Barouch, Dan H.

PY - 2022/12

Y1 - 2022/12

N2 - Developing an intervention that results in virologic control following discontinuation of antiretroviral therapy (ART) is a major objective of HIV-1 cure research. In this study, we investigated the therapeutic efficacy of a vaccine consisting of adenovirus serotype 26 (Ad26) and modified vaccinia Ankara (MVA) with or without an SIV Envelope (Env) gp140 protein with alum adjuvant in combination with the TLR7 agonist vesatolimod (GS-9620) in 36 ART-suppressed, SIVmac251-infected rhesus macaques. Ad26/MVA therapeutic vaccination led to robust humoral and cellular immune responses, and the Env protein boost increased antibody responses. Following discontinuation of ART, virologic control was observed in 5/12 animals in each vaccine group, compared with 0/12 animals in the sham control group. These data demonstrate therapeutic efficacy of Ad26/MVA vaccination with vesatolimod but no clear additional benefit of adding an Env protein boost. SIV-specific cellular immune responses correlated with virologic control. Our findings show partial efficacy of therapeutic vaccination following ART discontinuation in SIV-infected rhesus macaques.

AB - Developing an intervention that results in virologic control following discontinuation of antiretroviral therapy (ART) is a major objective of HIV-1 cure research. In this study, we investigated the therapeutic efficacy of a vaccine consisting of adenovirus serotype 26 (Ad26) and modified vaccinia Ankara (MVA) with or without an SIV Envelope (Env) gp140 protein with alum adjuvant in combination with the TLR7 agonist vesatolimod (GS-9620) in 36 ART-suppressed, SIVmac251-infected rhesus macaques. Ad26/MVA therapeutic vaccination led to robust humoral and cellular immune responses, and the Env protein boost increased antibody responses. Following discontinuation of ART, virologic control was observed in 5/12 animals in each vaccine group, compared with 0/12 animals in the sham control group. These data demonstrate therapeutic efficacy of Ad26/MVA vaccination with vesatolimod but no clear additional benefit of adding an Env protein boost. SIV-specific cellular immune responses correlated with virologic control. Our findings show partial efficacy of therapeutic vaccination following ART discontinuation in SIV-infected rhesus macaques.

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U2 - 10.1038/s41541-022-00477-x

DO - 10.1038/s41541-022-00477-x

M3 - Article

AN - SCOPUS:85130293060

SN - 2059-0105

VL - 7

JO - npj Vaccines

JF - npj Vaccines

IS - 1

M1 - 53

ER -

Therapeutic efficacy of an Ad26/MVA vaccine with SIV gp140 protein and vesatolimod in ART-suppressed rhesus macaques

Abstract

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