Vaccine plus microbicide effective in preventing vaginal SIV transmission in macaques

M. A. Rahman; M. Bissa; I. Silva de Castro; S. Helmold Hait; J. D. Stamos; F. Bhuyan; R. Hunegnaw; S. Sarkis; A. Gutowska; M. N. Doster; R. Moles; T. Hoang; L. M. Miller Jenkins; E. Appella; D. J. Venzon; H. Choo-Wosoba; T. Cardozo; M. M. Baum; D. H. Appella; M. Robert-Guroff; G. Franchini

doi:10.1038/s41564-023-01353-7

Vaccine plus microbicide effective in preventing vaginal SIV transmission in macaques

M. A. Rahman, M. Bissa, I. Silva de Castro, S. Helmold Hait, J. D. Stamos, F. Bhuyan, R. Hunegnaw, S. Sarkis, A. Gutowska, M. N. Doster, R. Moles, T. Hoang, L. M. Miller Jenkins, E. Appella, D. J. Venzon, H. Choo-Wosoba, T. Cardozo, M. M. Baum, D. H. Appella, M. Robert-GuroffG. Franchini

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

5 Scopus citations

Abstract

The human immunodeficiency virus epidemic continues in sub-Saharan Africa, and particularly affects adolescent girls and women who have limited access to antiretroviral therapy. Here we report that the risk of vaginal simian immunodeficiency virus (SIV)_mac251 acquisition is reduced by more than 90% using a combination of a vaccine comprising V1-deleted (V2 enhanced) SIV envelope immunogens with topical treatment of the zinc-finger inhibitor SAMT-247. Following 14 weekly intravaginal exposures to the highly pathogenic SIV_mac251, 80% of a cohort of 20 macaques vaccinated and treated with SAMT-247 remained uninfected. In an arm of 18 vaccinated-only animals without microbicide, 40% of macaques remained uninfected. The combined SAMT-247/vaccine regimen was significantly more effective than vaccination alone. By analysing immune correlates of protection, we show that, by increasing zinc availability, SAMT-247 increases natural killer cytotoxicity and monocyte efferocytosis, and decreases T-cell activation to augment vaccine-induced protection.

Original language	English
Pages (from-to)	905-918
Number of pages	14
Journal	Nature Microbiology
Volume	8
Issue number	5
DOIs	https://doi.org/10.1038/s41564-023-01353-7
State	Published - May 2023
Externally published	Yes

Scopus Subject Areas

Microbiology
Immunology
Applied Microbiology and Biotechnology
Genetics
Microbiology (medical)
Cell Biology

UN SDGs

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

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Rahman, M. A., Bissa, M., Silva de Castro, I., Helmold Hait, S., Stamos, J. D., Bhuyan, F., Hunegnaw, R., Sarkis, S., Gutowska, A., Doster, M. N., Moles, R., Hoang, T., Miller Jenkins, L. M., Appella, E., Venzon, D. J., Choo-Wosoba, H., Cardozo, T., Baum, M. M., Appella, D. H., ... Franchini, G. (2023). Vaccine plus microbicide effective in preventing vaginal SIV transmission in macaques. Nature Microbiology, 8(5), 905-918. https://doi.org/10.1038/s41564-023-01353-7

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title = "Vaccine plus microbicide effective in preventing vaginal SIV transmission in macaques",

abstract = "The human immunodeficiency virus epidemic continues in sub-Saharan Africa, and particularly affects adolescent girls and women who have limited access to antiretroviral therapy. Here we report that the risk of vaginal simian immunodeficiency virus (SIV)mac251 acquisition is reduced by more than 90% using a combination of a vaccine comprising V1-deleted (V2 enhanced) SIV envelope immunogens with topical treatment of the zinc-finger inhibitor SAMT-247. Following 14 weekly intravaginal exposures to the highly pathogenic SIVmac251, 80% of a cohort of 20 macaques vaccinated and treated with SAMT-247 remained uninfected. In an arm of 18 vaccinated-only animals without microbicide, 40% of macaques remained uninfected. The combined SAMT-247/vaccine regimen was significantly more effective than vaccination alone. By analysing immune correlates of protection, we show that, by increasing zinc availability, SAMT-247 increases natural killer cytotoxicity and monocyte efferocytosis, and decreases T-cell activation to augment vaccine-induced protection.",

author = "Rahman, {M. A.} and M. Bissa and {Silva de Castro}, I. and {Helmold Hait}, S. and Stamos, {J. D.} and F. Bhuyan and R. Hunegnaw and S. Sarkis and A. Gutowska and Doster, {M. N.} and R. Moles and T. Hoang and {Miller Jenkins}, {L. M.} and E. Appella and Venzon, {D. J.} and H. Choo-Wosoba and T. Cardozo and Baum, {M. M.} and Appella, {D. H.} and M. Robert-Guroff and G. Franchini",

note = "Publisher Copyright: {\textcopyright} 2023, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.",

year = "2023",

month = may,

doi = "10.1038/s41564-023-01353-7",

language = "English",

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Rahman, MA, Bissa, M, Silva de Castro, I, Helmold Hait, S, Stamos, JD, Bhuyan, F, Hunegnaw, R, Sarkis, S, Gutowska, A, Doster, MN, Moles, R, Hoang, T, Miller Jenkins, LM, Appella, E, Venzon, DJ, Choo-Wosoba, H, Cardozo, T, Baum, MM, Appella, DH, Robert-Guroff, M & Franchini, G 2023, 'Vaccine plus microbicide effective in preventing vaginal SIV transmission in macaques', Nature Microbiology, vol. 8, no. 5, pp. 905-918. https://doi.org/10.1038/s41564-023-01353-7

TY - JOUR

T1 - Vaccine plus microbicide effective in preventing vaginal SIV transmission in macaques

AU - Rahman, M. A.

AU - Bissa, M.

AU - Silva de Castro, I.

AU - Helmold Hait, S.

AU - Stamos, J. D.

AU - Bhuyan, F.

AU - Hunegnaw, R.

AU - Sarkis, S.

AU - Gutowska, A.

AU - Doster, M. N.

AU - Moles, R.

AU - Hoang, T.

AU - Miller Jenkins, L. M.

AU - Appella, E.

AU - Venzon, D. J.

AU - Choo-Wosoba, H.

AU - Cardozo, T.

AU - Baum, M. M.

AU - Appella, D. H.

AU - Robert-Guroff, M.

AU - Franchini, G.

PY - 2023/5

Y1 - 2023/5

N2 - The human immunodeficiency virus epidemic continues in sub-Saharan Africa, and particularly affects adolescent girls and women who have limited access to antiretroviral therapy. Here we report that the risk of vaginal simian immunodeficiency virus (SIV)mac251 acquisition is reduced by more than 90% using a combination of a vaccine comprising V1-deleted (V2 enhanced) SIV envelope immunogens with topical treatment of the zinc-finger inhibitor SAMT-247. Following 14 weekly intravaginal exposures to the highly pathogenic SIVmac251, 80% of a cohort of 20 macaques vaccinated and treated with SAMT-247 remained uninfected. In an arm of 18 vaccinated-only animals without microbicide, 40% of macaques remained uninfected. The combined SAMT-247/vaccine regimen was significantly more effective than vaccination alone. By analysing immune correlates of protection, we show that, by increasing zinc availability, SAMT-247 increases natural killer cytotoxicity and monocyte efferocytosis, and decreases T-cell activation to augment vaccine-induced protection.

AB - The human immunodeficiency virus epidemic continues in sub-Saharan Africa, and particularly affects adolescent girls and women who have limited access to antiretroviral therapy. Here we report that the risk of vaginal simian immunodeficiency virus (SIV)mac251 acquisition is reduced by more than 90% using a combination of a vaccine comprising V1-deleted (V2 enhanced) SIV envelope immunogens with topical treatment of the zinc-finger inhibitor SAMT-247. Following 14 weekly intravaginal exposures to the highly pathogenic SIVmac251, 80% of a cohort of 20 macaques vaccinated and treated with SAMT-247 remained uninfected. In an arm of 18 vaccinated-only animals without microbicide, 40% of macaques remained uninfected. The combined SAMT-247/vaccine regimen was significantly more effective than vaccination alone. By analysing immune correlates of protection, we show that, by increasing zinc availability, SAMT-247 increases natural killer cytotoxicity and monocyte efferocytosis, and decreases T-cell activation to augment vaccine-induced protection.

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DO - 10.1038/s41564-023-01353-7

M3 - Article

C2 - 37024617

AN - SCOPUS:85151733622

SN - 2058-5276

VL - 8

SP - 905

EP - 918

JO - Nature Microbiology

JF - Nature Microbiology

IS - 5

ER -

Vaccine plus microbicide effective in preventing vaginal SIV transmission in macaques

Abstract

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UN SDGs

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