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 and Nancy L. Haigwood ()
Additional contact information
Mariya B. Shapiro: Oregon Health & Science University
Tracy Cheever: Oregon Health & Science University
Delphine C. Malherbe: Oregon Health & Science University
Shilpi Pandey: Oregon Health & Science University
Jason Reed: Oregon Health & Science University
Eun Sung Yang: Vaccine Research Center, NIAID/NIH
Keyun Wang: Vaccine Research Center, NIAID/NIH
Amarendra Pegu: Vaccine Research Center, NIAID/NIH
Xuejun Chen: Vaccine Research Center, NIAID/NIH
Don Siess: Oregon Health & Science University
David Burke: Oregon Health & Science University
Heidi Henderson: Oregon Health & Science University
Rebecca Lewinsohn: Oregon Health & Science University
Miranda Fischer: Oregon Health & Science University
Jeffrey J. Stanton: Oregon Health & Science University
Michael K. Axthelm: Oregon Health & Science University
Christoph Kahl: Oregon Health & Science University
Byung Park: Oregon Health & Science University
Anne D. Lewis: Oregon Health & Science University
Jonah B. Sacha: Oregon Health & Science University
John R. Mascola: Vaccine Research Center, NIAID/NIH
Ann J. Hessell: Oregon Health & Science University
Nancy L. Haigwood: Oregon Health & Science University

Nature Communications, 2020, vol. 11, issue 1, 1-13

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-019-13972-y

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