Early short-term treatment with neutralizing human monoclonal antibodies halts SHIV infection in infant macaques

Ann J. Hessell; J. Pablo Jaworski; Erin Epson; Kenta Matsuda; Shilpi Pandey; Christoph Kahl; Jason Reed; William F. Sutton; Katherine B. Hammond; Tracy A. Cheever; Philip T. Barnette; Alfred W. Legasse; Shannon Planer; Jeffrey J. Stanton; Amarendra Pegu; Xuejun Chen; Keyun Wang; Don Siess; David Burke; Byung S. Park; Michael K. Axthelm; Anne Lewis; Vanessa M. Hirsch; Barney S. Graham; John R. Mascola; Jonah B. Sacha; Nancy L. Haigwood

doi:10.1038/nm.4063

Early short-term treatment with neutralizing human monoclonal antibodies halts SHIV infection in infant macaques

Ann J. Hessell, J. Pablo Jaworski, Erin Epson, Kenta Matsuda, Shilpi Pandey, Christoph Kahl, Jason Reed, William F. Sutton, Katherine B. Hammond, Tracy A. Cheever, Philip T. Barnette, Alfred W. Legasse, Shannon Planer, Jeffrey J. Stanton, Amarendra Pegu, Xuejun Chen, Keyun Wang, Don Siess, David Burke, Byung S. ParkMichael K. Axthelm, Anne Lewis, Vanessa M. Hirsch, Barney S. Graham, John R. Mascola, Jonah B. Sacha, Nancy L. Haigwood

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

143 Scopus citations

Abstract

Prevention of mother-to-child transmission (MTCT) of HIV remains a major objective where antenatal care is not readily accessible. We tested HIV-1-specific human neutralizing monoclonal antibodies (NmAbs) as a post-exposure therapy in an infant macaque model for intrapartum MTCT. One-month-old rhesus macaques were inoculated orally with the simian-human immunodeficiency virus SHIV SF162P3. On days 1, 4, 7 and 10 after virus exposure, we injected animals subcutaneously with NmAbs and quantified systemic distribution of NmAbs in multiple tissues within 24 h after antibody administration. Replicating virus was found in multiple tissues by day 1 in animals that were not treated. All NmAb-treated macaques were free of virus in blood and tissues at 6 months after exposure. We detected no anti-SHIV T cell responses in blood or tissues at necropsy, and no virus emerged after CD8 + T cell depletion. These results suggest that early passive immunotherapy can eliminate early viral foci and thereby prevent the establishment of viral reservoirs.

Original language	English (US)
Pages (from-to)	362-368
Number of pages	7
Journal	Nature medicine
Volume	22
Issue number	4
DOIs	https://doi.org/10.1038/nm.4063
State	Published - Apr 1 2016

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

Access to Document

10.1038/nm.4063

Cite this

Hessell, A. J., Jaworski, J. P., Epson, E., Matsuda, K., Pandey, S., Kahl, C., Reed, J., Sutton, W. F., Hammond, K. B., Cheever, T. A., Barnette, P. T., Legasse, A. W., Planer, S., Stanton, J. J., Pegu, A., Chen, X., Wang, K., Siess, D., Burke, D., ... Haigwood, N. L. (2016). Early short-term treatment with neutralizing human monoclonal antibodies halts SHIV infection in infant macaques. Nature medicine, 22(4), 362-368. https://doi.org/10.1038/nm.4063

Hessell, AJ, Jaworski, JP, Epson, E, Matsuda, K, Pandey, S, Kahl, C, Reed, J, Sutton, WF, Hammond, KB, Cheever, TA, Barnette, PT, Legasse, AW, Planer, S, Stanton, JJ, Pegu, A, Chen, X, Wang, K, Siess, D, Burke, D, Park, BS , Axthelm, MK , Lewis, A, Hirsch, VM, Graham, BS, Mascola, JR, Sacha, JB & Haigwood, NL 2016, 'Early short-term treatment with neutralizing human monoclonal antibodies halts SHIV infection in infant macaques', Nature medicine, vol. 22, no. 4, pp. 362-368. https://doi.org/10.1038/nm.4063

@article{d5f311134b414294a980163cdf4a38b7,

title = "Early short-term treatment with neutralizing human monoclonal antibodies halts SHIV infection in infant macaques",

abstract = "Prevention of mother-to-child transmission (MTCT) of HIV remains a major objective where antenatal care is not readily accessible. We tested HIV-1-specific human neutralizing monoclonal antibodies (NmAbs) as a post-exposure therapy in an infant macaque model for intrapartum MTCT. One-month-old rhesus macaques were inoculated orally with the simian-human immunodeficiency virus SHIV SF162P3. On days 1, 4, 7 and 10 after virus exposure, we injected animals subcutaneously with NmAbs and quantified systemic distribution of NmAbs in multiple tissues within 24 h after antibody administration. Replicating virus was found in multiple tissues by day 1 in animals that were not treated. All NmAb-treated macaques were free of virus in blood and tissues at 6 months after exposure. We detected no anti-SHIV T cell responses in blood or tissues at necropsy, and no virus emerged after CD8 + T cell depletion. These results suggest that early passive immunotherapy can eliminate early viral foci and thereby prevent the establishment of viral reservoirs.",

author = "Hessell, {Ann J.} and Jaworski, {J. Pablo} and Erin Epson and Kenta Matsuda and Shilpi Pandey and Christoph Kahl and Jason Reed and Sutton, {William F.} and Hammond, {Katherine B.} and Cheever, {Tracy A.} and Barnette, {Philip T.} and Legasse, {Alfred W.} and Shannon Planer and Stanton, {Jeffrey J.} and Amarendra Pegu and Xuejun Chen and Keyun Wang and Don Siess and David Burke and Park, {Byung S.} and Axthelm, {Michael K.} and Anne Lewis and Hirsch, {Vanessa M.} and Graham, {Barney S.} and Mascola, {John R.} and Sacha, {Jonah B.} and Haigwood, {Nancy L.}",

year = "2016",

month = apr,

day = "1",

doi = "10.1038/nm.4063",

language = "English (US)",

volume = "22",

pages = "362--368",

journal = "Nature medicine",

issn = "1078-8956",

publisher = "Nature Publishing Group",

number = "4",

}

TY - JOUR

T1 - Early short-term treatment with neutralizing human monoclonal antibodies halts SHIV infection in infant macaques

AU - Hessell, Ann J.

AU - Jaworski, J. Pablo

AU - Epson, Erin

AU - Matsuda, Kenta

AU - Pandey, Shilpi

AU - Kahl, Christoph

AU - Reed, Jason

AU - Sutton, William F.

AU - Hammond, Katherine B.

AU - Cheever, Tracy A.

AU - Barnette, Philip T.

AU - Legasse, Alfred W.

AU - Planer, Shannon

AU - Stanton, Jeffrey J.

AU - Pegu, Amarendra

AU - Chen, Xuejun

AU - Wang, Keyun

AU - Siess, Don

AU - Burke, David

AU - Park, Byung S.

AU - Axthelm, Michael K.

AU - Lewis, Anne

AU - Hirsch, Vanessa M.

AU - Graham, Barney S.

AU - Mascola, John R.

AU - Sacha, Jonah B.

AU - Haigwood, Nancy L.

PY - 2016/4/1

Y1 - 2016/4/1

N2 - Prevention of mother-to-child transmission (MTCT) of HIV remains a major objective where antenatal care is not readily accessible. We tested HIV-1-specific human neutralizing monoclonal antibodies (NmAbs) as a post-exposure therapy in an infant macaque model for intrapartum MTCT. One-month-old rhesus macaques were inoculated orally with the simian-human immunodeficiency virus SHIV SF162P3. On days 1, 4, 7 and 10 after virus exposure, we injected animals subcutaneously with NmAbs and quantified systemic distribution of NmAbs in multiple tissues within 24 h after antibody administration. Replicating virus was found in multiple tissues by day 1 in animals that were not treated. All NmAb-treated macaques were free of virus in blood and tissues at 6 months after exposure. We detected no anti-SHIV T cell responses in blood or tissues at necropsy, and no virus emerged after CD8 + T cell depletion. These results suggest that early passive immunotherapy can eliminate early viral foci and thereby prevent the establishment of viral reservoirs.

AB - Prevention of mother-to-child transmission (MTCT) of HIV remains a major objective where antenatal care is not readily accessible. We tested HIV-1-specific human neutralizing monoclonal antibodies (NmAbs) as a post-exposure therapy in an infant macaque model for intrapartum MTCT. One-month-old rhesus macaques were inoculated orally with the simian-human immunodeficiency virus SHIV SF162P3. On days 1, 4, 7 and 10 after virus exposure, we injected animals subcutaneously with NmAbs and quantified systemic distribution of NmAbs in multiple tissues within 24 h after antibody administration. Replicating virus was found in multiple tissues by day 1 in animals that were not treated. All NmAb-treated macaques were free of virus in blood and tissues at 6 months after exposure. We detected no anti-SHIV T cell responses in blood or tissues at necropsy, and no virus emerged after CD8 + T cell depletion. These results suggest that early passive immunotherapy can eliminate early viral foci and thereby prevent the establishment of viral reservoirs.

UR - http://www.scopus.com/inward/record.url?scp=84961392349&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84961392349&partnerID=8YFLogxK

U2 - 10.1038/nm.4063

DO - 10.1038/nm.4063

M3 - Article

C2 - 26998834

AN - SCOPUS:84961392349

SN - 1078-8956

VL - 22

SP - 362

EP - 368

JO - Nature medicine

JF - Nature medicine

IS - 4

ER -

Early short-term treatment with neutralizing human monoclonal antibodies halts SHIV infection in infant macaques

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this