Single-dose bNAb cocktail or abbreviated ART post-exposure regimens achieve tight SHIV control without adaptive immunity

Mariya B. Shapiro; Tracy Cheever; Delphine C. Malherbe; Shilpi Pandey; Jason Reed; Eun Sung Yang; Keyun Wang; Amarendra Pegu; Xuejun Chen; Don Siess; David Burke; Heidi Henderson; Rebecca Lewinsohn; Miranda Fischer; Jeffrey J. Stanton; Michael K. Axthelm; Christoph Kahl; Byung Park; Anne D. Lewis; Jonah B. Sacha; John R. Mascola; Ann J. Hessell; Nancy L. Haigwood

doi:10.1038/s41467-019-13972-y

Single-dose bNAb cocktail or abbreviated ART post-exposure regimens achieve tight SHIV control without adaptive immunity

Mariya B. Shapiro, Tracy Cheever, Delphine C. Malherbe, Shilpi Pandey, Jason Reed, Eun Sung Yang, Keyun Wang, Amarendra Pegu, Xuejun Chen, Don Siess, David Burke, Heidi Henderson, Rebecca Lewinsohn, Miranda Fischer, Jeffrey J. Stanton, Michael K. Axthelm, Christoph Kahl, Byung Park, Anne D. Lewis, Jonah B. SachaJohn R. Mascola, Ann J. Hessell, Nancy L. Haigwood

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Abstract

Vertical transmission accounts for most human immunodeficiency virus (HIV) infection in children, and treatments for newborns are needed to abrogate infection or limit disease progression. We showed previously that short-term broadly neutralizing antibody (bNAb) therapy given 24 h after oral exposure cleared simian-human immunodeficiency virus (SHIV) in a macaque model of perinatal infection. Here, we report that all infants given either a single dose of bNAbs at 30 h, or a 21-day triple-drug ART regimen at 48 h, are aviremic with almost no virus in tissues. In contrast, bNAb treatment beginning at 48 h leads to tight control without adaptive immune responses in half of animals. We conclude that both bNAbs and ART mediate effective post-exposure prophylaxis in infant macaques within 30–48 h of oral SHIV exposure. Our findings suggest that optimizing the treatment regimen may extend the window of opportunity for preventing perinatal HIV infection when treatment is delayed.

Original language	English (US)
Article number	70
Journal	Nature communications
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-13972-y
State	Published - Dec 1 2020

ASJC Scopus subject areas

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

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Shapiro, M. B., Cheever, T., Malherbe, D. C., Pandey, S., Reed, J., Yang, E. S., Wang, K., Pegu, A., Chen, X., Siess, D., Burke, D., Henderson, H., Lewinsohn, R., Fischer, M., Stanton, J. J., Axthelm, M. K., Kahl, C., Park, B., Lewis, A. D., ... Haigwood, N. L. (2020). Single-dose bNAb cocktail or abbreviated ART post-exposure regimens achieve tight SHIV control without adaptive immunity. Nature communications, 11(1), Article 70. https://doi.org/10.1038/s41467-019-13972-y

Shapiro, MB, Cheever, T, Malherbe, DC, Pandey, S, Reed, J, Yang, ES, Wang, K, Pegu, A, Chen, X, Siess, D, Burke, D, Henderson, H, Lewinsohn, R, Fischer, M, Stanton, JJ , Axthelm, MK, Kahl, C, Park, B , Lewis, AD , Sacha, JB, Mascola, JR, Hessell, AJ & Haigwood, NL 2020, 'Single-dose bNAb cocktail or abbreviated ART post-exposure regimens achieve tight SHIV control without adaptive immunity', Nature communications, vol. 11, no. 1, 70. https://doi.org/10.1038/s41467-019-13972-y

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title = "Single-dose bNAb cocktail or abbreviated ART post-exposure regimens achieve tight SHIV control without adaptive immunity",

abstract = "Vertical transmission accounts for most human immunodeficiency virus (HIV) infection in children, and treatments for newborns are needed to abrogate infection or limit disease progression. We showed previously that short-term broadly neutralizing antibody (bNAb) therapy given 24 h after oral exposure cleared simian-human immunodeficiency virus (SHIV) in a macaque model of perinatal infection. Here, we report that all infants given either a single dose of bNAbs at 30 h, or a 21-day triple-drug ART regimen at 48 h, are aviremic with almost no virus in tissues. In contrast, bNAb treatment beginning at 48 h leads to tight control without adaptive immune responses in half of animals. We conclude that both bNAbs and ART mediate effective post-exposure prophylaxis in infant macaques within 30–48 h of oral SHIV exposure. Our findings suggest that optimizing the treatment regimen may extend the window of opportunity for preventing perinatal HIV infection when treatment is delayed.",

author = "Shapiro, {Mariya B.} and Tracy Cheever and Malherbe, {Delphine C.} and Shilpi Pandey and Jason Reed and Yang, {Eun Sung} and Keyun Wang and Amarendra Pegu and Xuejun Chen and Don Siess and David Burke and Heidi Henderson and Rebecca Lewinsohn and Miranda Fischer and Stanton, {Jeffrey J.} and Axthelm, {Michael K.} and Christoph Kahl and Byung Park and Lewis, {Anne D.} and Sacha, {Jonah B.} and Mascola, {John R.} and Hessell, {Ann J.} and Haigwood, {Nancy L.}",

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AU - Cheever, Tracy

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AU - Pandey, Shilpi

AU - Reed, Jason

AU - Yang, Eun Sung

AU - Wang, Keyun

AU - Pegu, Amarendra

AU - Chen, Xuejun

AU - Siess, Don

AU - Burke, David

AU - Henderson, Heidi

AU - Lewinsohn, Rebecca

AU - Fischer, Miranda

AU - Stanton, Jeffrey J.

AU - Axthelm, Michael K.

AU - Kahl, Christoph

AU - Park, Byung

AU - Lewis, Anne D.

AU - Sacha, Jonah B.

AU - Mascola, John R.

AU - Hessell, Ann J.

AU - Haigwood, Nancy L.

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N2 - Vertical transmission accounts for most human immunodeficiency virus (HIV) infection in children, and treatments for newborns are needed to abrogate infection or limit disease progression. We showed previously that short-term broadly neutralizing antibody (bNAb) therapy given 24 h after oral exposure cleared simian-human immunodeficiency virus (SHIV) in a macaque model of perinatal infection. Here, we report that all infants given either a single dose of bNAbs at 30 h, or a 21-day triple-drug ART regimen at 48 h, are aviremic with almost no virus in tissues. In contrast, bNAb treatment beginning at 48 h leads to tight control without adaptive immune responses in half of animals. We conclude that both bNAbs and ART mediate effective post-exposure prophylaxis in infant macaques within 30–48 h of oral SHIV exposure. Our findings suggest that optimizing the treatment regimen may extend the window of opportunity for preventing perinatal HIV infection when treatment is delayed.

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Single-dose bNAb cocktail or abbreviated ART post-exposure regimens achieve tight SHIV control without adaptive immunity

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