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

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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 (US)
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

ASJC Scopus subject areas

General
General Physics and Astronomy
General Chemistry
General Biochemistry, Genetics and Molecular Biology

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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

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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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.}",

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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

Y1 - 2022/12

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.

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

Abstract

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