Neutralizing Antibodies Protect against Oral Transmission of Lymphocryptovirus
Summary: Epstein-Barr virus (EBV) is a cancer-associated pathogen for which there is no vaccine. Successful anti-viral vaccines elicit antibodies that neutralize infectivity; however, it is unknown whether neutralizing antibodies prevent EBV acquisition. Here we assessed whether passively delivered...
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doaj-5a07c5ee5e3746b3b84e49969e6834a52020-11-25T04:00:15ZengElsevierCell Reports Medicine2666-37912020-06-0113100033Neutralizing Antibodies Protect against Oral Transmission of LymphocryptovirusSwati Singh0Leah J. Homad1Nicholas R. Akins2Claire M. Stoffers3Stefan Lackhar4Harman Malhi5Yu-Hsin Wan6David J. Rawlings7Andrew T. McGuire8Center for Immunity and Immunotherapies and Program for Cell and Gene Therapy, Seattle Children’s Research Institute, Seattle, WA 98101, USAVaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USAVaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USACenter for Immunity and Immunotherapies and Program for Cell and Gene Therapy, Seattle Children’s Research Institute, Seattle, WA 98101, USACenter for Immunity and Immunotherapies and Program for Cell and Gene Therapy, Seattle Children’s Research Institute, Seattle, WA 98101, USAVaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USAVaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USACenter for Immunity and Immunotherapies and Program for Cell and Gene Therapy, Seattle Children’s Research Institute, Seattle, WA 98101, USA; Departments of Pediatrics and Immunology, University of Washington, Seattle, WA 98101, USA; Corresponding authorVaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Department of Global Health, University of Washington, Seattle, WA 98195, USA; Corresponding authorSummary: Epstein-Barr virus (EBV) is a cancer-associated pathogen for which there is no vaccine. Successful anti-viral vaccines elicit antibodies that neutralize infectivity; however, it is unknown whether neutralizing antibodies prevent EBV acquisition. Here we assessed whether passively delivered AMMO1, a monoclonal antibody that neutralizes EBV in a cell-type-independent manner, could protect against experimental EBV challenge in two animal infection models. When present prior to a high-dose intravenous EBV challenge, AMMO1 prevented viremia and reduced viral loads to nearly undetectable levels in humanized mice. AMMO1 conferred sterilizing immunity to three of four macaques challenged orally with rhesus lymphocryptovirus, the EBV ortholog that infects rhesus macaques. The infected macaque had lower plasma neutralizing activity than the protected animals. These results indicate that a vaccine capable of eliciting adequate titers of neutralizing antibodies targeting the AMMO1 epitope may protect against EBV acquisition and are therefore highly relevant to the design of an effective EBV vaccine.http://www.sciencedirect.com/science/article/pii/S2666379120300458 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Swati Singh Leah J. Homad Nicholas R. Akins Claire M. Stoffers Stefan Lackhar Harman Malhi Yu-Hsin Wan David J. Rawlings Andrew T. McGuire |
spellingShingle |
Swati Singh Leah J. Homad Nicholas R. Akins Claire M. Stoffers Stefan Lackhar Harman Malhi Yu-Hsin Wan David J. Rawlings Andrew T. McGuire Neutralizing Antibodies Protect against Oral Transmission of Lymphocryptovirus Cell Reports Medicine |
author_facet |
Swati Singh Leah J. Homad Nicholas R. Akins Claire M. Stoffers Stefan Lackhar Harman Malhi Yu-Hsin Wan David J. Rawlings Andrew T. McGuire |
author_sort |
Swati Singh |
title |
Neutralizing Antibodies Protect against Oral Transmission of Lymphocryptovirus |
title_short |
Neutralizing Antibodies Protect against Oral Transmission of Lymphocryptovirus |
title_full |
Neutralizing Antibodies Protect against Oral Transmission of Lymphocryptovirus |
title_fullStr |
Neutralizing Antibodies Protect against Oral Transmission of Lymphocryptovirus |
title_full_unstemmed |
Neutralizing Antibodies Protect against Oral Transmission of Lymphocryptovirus |
title_sort |
neutralizing antibodies protect against oral transmission of lymphocryptovirus |
publisher |
Elsevier |
series |
Cell Reports Medicine |
issn |
2666-3791 |
publishDate |
2020-06-01 |
description |
Summary: Epstein-Barr virus (EBV) is a cancer-associated pathogen for which there is no vaccine. Successful anti-viral vaccines elicit antibodies that neutralize infectivity; however, it is unknown whether neutralizing antibodies prevent EBV acquisition. Here we assessed whether passively delivered AMMO1, a monoclonal antibody that neutralizes EBV in a cell-type-independent manner, could protect against experimental EBV challenge in two animal infection models. When present prior to a high-dose intravenous EBV challenge, AMMO1 prevented viremia and reduced viral loads to nearly undetectable levels in humanized mice. AMMO1 conferred sterilizing immunity to three of four macaques challenged orally with rhesus lymphocryptovirus, the EBV ortholog that infects rhesus macaques. The infected macaque had lower plasma neutralizing activity than the protected animals. These results indicate that a vaccine capable of eliciting adequate titers of neutralizing antibodies targeting the AMMO1 epitope may protect against EBV acquisition and are therefore highly relevant to the design of an effective EBV vaccine. |
url |
http://www.sciencedirect.com/science/article/pii/S2666379120300458 |
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