Therapeutic efficacy of combined active and passive immunization in ART-suppressed, SHIV-infected rhesus macaques

Victoria E.K. Walker-Sperling; Noe B. Mercado; Abishek Chandrashekar; Erica N. Borducchi; Jinyan Liu; Joseph P. Nkolola; Mark Lewis; Jeffrey P. Murry; Yunling Yang; Romas Geleziunas; Merlin L. Robb; Nelson L. Michael; Maria G. Pau; Frank Wegmann; Hanneke Schuitemaker; Emily J. Fray; Mithra R. Kumar; Janet D. Siliciano; Robert F. Siliciano; Dan H. Barouch

doi:10.1038/s41467-022-31196-5

Therapeutic efficacy of combined active and passive immunization in ART-suppressed, SHIV-infected rhesus macaques

Victoria E.K. Walker-Sperling
, Noe B. Mercado
, Abishek Chandrashekar
, Erica N. Borducchi
, Jinyan Liu
, Joseph P. Nkolola
, Mark Lewis
, Jeffrey P. Murry
, Yunling Yang
, Romas Geleziunas
, Merlin L. Robb
, Nelson L. Michael
, Maria G. Pau
, Frank Wegmann
, Hanneke Schuitemaker
, Emily J. Fray
, Mithra R. Kumar
, Janet D. Siliciano
, Robert F. Siliciano
, Dan H. Barouch^*

^*Corresponding author for this work

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

28 Scopus citations

Abstract

The latent viral reservoir is the critical barrier for developing an HIV-1 cure. Previous studies have shown that therapeutic vaccination or broadly neutralizing antibody (bNAb) administration, together with a Toll-like receptor 7 (TLR7) agonist, enhanced virologic control or delayed viral rebound, respectively, following discontinuation of antiretroviral therapy (ART) in SIV- or SHIV-infected rhesus macaques. Here we show that the combination of active and passive immunization with vesatolimod may lead to higher rates of post-ART virologic control compared to either approach alone. Therapeutic Ad26/MVA vaccination and PGT121 administration together with TLR7 stimulation with vesatolimod resulted in 70% post-ART virologic control in SHIV-SF162P3-infected rhesus macaques. These data suggest the potential of combining active and passive immunization targeting different immunologic mechanisms as an HIV-1 cure strategy.

Original language	English
Article number	3463
Journal	Nature Communications
Volume	13
Issue number	1
DOIs	https://doi.org/10.1038/s41467-022-31196-5
State	Published - Dec 2022

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Walker-Sperling, V. E. K., Mercado, N. B., Chandrashekar, A., Borducchi, E. N., Liu, J., Nkolola, J. P., Lewis, M., Murry, J. P., Yang, Y., Geleziunas, R., Robb, M. L., Michael, N. L., Pau, M. G., Wegmann, F., Schuitemaker, H., Fray, E. J., Kumar, M. R., Siliciano, J. D., Siliciano, R. F., & Barouch, D. H. (2022). Therapeutic efficacy of combined active and passive immunization in ART-suppressed, SHIV-infected rhesus macaques. Nature Communications, 13(1), Article 3463. https://doi.org/10.1038/s41467-022-31196-5

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title = "Therapeutic efficacy of combined active and passive immunization in ART-suppressed, SHIV-infected rhesus macaques",

abstract = "The latent viral reservoir is the critical barrier for developing an HIV-1 cure. Previous studies have shown that therapeutic vaccination or broadly neutralizing antibody (bNAb) administration, together with a Toll-like receptor 7 (TLR7) agonist, enhanced virologic control or delayed viral rebound, respectively, following discontinuation of antiretroviral therapy (ART) in SIV- or SHIV-infected rhesus macaques. Here we show that the combination of active and passive immunization with vesatolimod may lead to higher rates of post-ART virologic control compared to either approach alone. Therapeutic Ad26/MVA vaccination and PGT121 administration together with TLR7 stimulation with vesatolimod resulted in 70\% post-ART virologic control in SHIV-SF162P3-infected rhesus macaques. These data suggest the potential of combining active and passive immunization targeting different immunologic mechanisms as an HIV-1 cure strategy.",

author = "Walker-Sperling, \{Victoria E.K.\} and Mercado, \{Noe B.\} and Abishek Chandrashekar and Borducchi, \{Erica N.\} and Jinyan Liu and Nkolola, \{Joseph P.\} and Mark Lewis and Murry, \{Jeffrey P.\} and Yunling Yang and Romas Geleziunas and Robb, \{Merlin L.\} and Michael, \{Nelson L.\} 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 Barouch, \{Dan H.\}",

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

year = "2022",

month = dec,

doi = "10.1038/s41467-022-31196-5",

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Walker-Sperling, VEK, Mercado, NB, Chandrashekar, A, Borducchi, EN, Liu, J, Nkolola, JP, Lewis, M, Murry, JP, Yang, Y, Geleziunas, R, Robb, ML , Michael, NL, Pau, MG, Wegmann, F, Schuitemaker, H, Fray, EJ, Kumar, MR, Siliciano, JD, Siliciano, RF & Barouch, DH 2022, 'Therapeutic efficacy of combined active and passive immunization in ART-suppressed, SHIV-infected rhesus macaques', Nature Communications, vol. 13, no. 1, 3463. https://doi.org/10.1038/s41467-022-31196-5

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AU - Walker-Sperling, Victoria E.K.

AU - Mercado, Noe B.

AU - Chandrashekar, Abishek

AU - Borducchi, Erica N.

AU - Liu, Jinyan

AU - Nkolola, Joseph P.

AU - Lewis, Mark

AU - Murry, Jeffrey P.

AU - Yang, Yunling

AU - Geleziunas, Romas

AU - Robb, Merlin L.

AU - Michael, Nelson L.

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 - Barouch, Dan H.

PY - 2022/12

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N2 - The latent viral reservoir is the critical barrier for developing an HIV-1 cure. Previous studies have shown that therapeutic vaccination or broadly neutralizing antibody (bNAb) administration, together with a Toll-like receptor 7 (TLR7) agonist, enhanced virologic control or delayed viral rebound, respectively, following discontinuation of antiretroviral therapy (ART) in SIV- or SHIV-infected rhesus macaques. Here we show that the combination of active and passive immunization with vesatolimod may lead to higher rates of post-ART virologic control compared to either approach alone. Therapeutic Ad26/MVA vaccination and PGT121 administration together with TLR7 stimulation with vesatolimod resulted in 70% post-ART virologic control in SHIV-SF162P3-infected rhesus macaques. These data suggest the potential of combining active and passive immunization targeting different immunologic mechanisms as an HIV-1 cure strategy.

AB - The latent viral reservoir is the critical barrier for developing an HIV-1 cure. Previous studies have shown that therapeutic vaccination or broadly neutralizing antibody (bNAb) administration, together with a Toll-like receptor 7 (TLR7) agonist, enhanced virologic control or delayed viral rebound, respectively, following discontinuation of antiretroviral therapy (ART) in SIV- or SHIV-infected rhesus macaques. Here we show that the combination of active and passive immunization with vesatolimod may lead to higher rates of post-ART virologic control compared to either approach alone. Therapeutic Ad26/MVA vaccination and PGT121 administration together with TLR7 stimulation with vesatolimod resulted in 70% post-ART virologic control in SHIV-SF162P3-infected rhesus macaques. These data suggest the potential of combining active and passive immunization targeting different immunologic mechanisms as an HIV-1 cure strategy.

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SN - 2041-1723

VL - 13

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 3463

ER -

Therapeutic efficacy of combined active and passive immunization in ART-suppressed, SHIV-infected rhesus macaques

Abstract

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