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...

Full description

Bibliographic Details
Main Authors: Swati Singh, Leah J. Homad, Nicholas R. Akins, Claire M. Stoffers, Stefan Lackhar, Harman Malhi, Yu-Hsin Wan, David J. Rawlings, Andrew T. McGuire
Format: Article
Language:English
Published: Elsevier 2020-06-01
Series:Cell Reports Medicine
Online Access:http://www.sciencedirect.com/science/article/pii/S2666379120300458
id doaj-5a07c5ee5e3746b3b84e49969e6834a5
record_format Article
spelling 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
work_keys_str_mv AT swatisingh neutralizingantibodiesprotectagainstoraltransmissionoflymphocryptovirus
AT leahjhomad neutralizingantibodiesprotectagainstoraltransmissionoflymphocryptovirus
AT nicholasrakins neutralizingantibodiesprotectagainstoraltransmissionoflymphocryptovirus
AT clairemstoffers neutralizingantibodiesprotectagainstoraltransmissionoflymphocryptovirus
AT stefanlackhar neutralizingantibodiesprotectagainstoraltransmissionoflymphocryptovirus
AT harmanmalhi neutralizingantibodiesprotectagainstoraltransmissionoflymphocryptovirus
AT yuhsinwan neutralizingantibodiesprotectagainstoraltransmissionoflymphocryptovirus
AT davidjrawlings neutralizingantibodiesprotectagainstoraltransmissionoflymphocryptovirus
AT andrewtmcguire neutralizingantibodiesprotectagainstoraltransmissionoflymphocryptovirus
_version_ 1724451590139543552