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A conditionally replication-defective cytomegalovirus vaccine elicits potent and diverse functional monoclonal antibodies in a phase I clinical trial

A conditionally replication-defective human cytomegalovirus (HCMV) vaccine, V160, was shown to be safe and immunogenic in a two-part, double-blind, randomized, placebo-controlled phase I clinical trial (NCT01986010). However, the specificities and functional properties of V160-elicited antibodies re...

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Autores principales: Li, Leike, Freed, Daniel C., Liu, Yaping, Li, Fengsheng, Barrett, Diane F., Xiong, Wei, Ye, Xiaohua, Adler, Stuart P., Rupp, Richard E., Wang, Dai, Zhang, Ningyan, Fu, Tong-Ming, An, Zhiqiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172929/
https://www.ncbi.nlm.nih.gov/pubmed/34078915
http://dx.doi.org/10.1038/s41541-021-00342-3
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author Li, Leike
Freed, Daniel C.
Liu, Yaping
Li, Fengsheng
Barrett, Diane F.
Xiong, Wei
Ye, Xiaohua
Adler, Stuart P.
Rupp, Richard E.
Wang, Dai
Zhang, Ningyan
Fu, Tong-Ming
An, Zhiqiang
author_facet Li, Leike
Freed, Daniel C.
Liu, Yaping
Li, Fengsheng
Barrett, Diane F.
Xiong, Wei
Ye, Xiaohua
Adler, Stuart P.
Rupp, Richard E.
Wang, Dai
Zhang, Ningyan
Fu, Tong-Ming
An, Zhiqiang
author_sort Li, Leike
collection PubMed
description A conditionally replication-defective human cytomegalovirus (HCMV) vaccine, V160, was shown to be safe and immunogenic in a two-part, double-blind, randomized, placebo-controlled phase I clinical trial (NCT01986010). However, the specificities and functional properties of V160-elicited antibodies remain undefined. Here, we characterized 272 monoclonal antibodies (mAbs) isolated from single memory B cells of six V160-vaccinated subjects. The mAbs bind to diverse HCMV antigens, including multiple components of the pentamer, gB, and tegument proteins. The most-potent neutralizing antibodies target the pentamer-UL subunits. The binding sites of the antibodies overlap with those of antibodies responding to natural HCMV infection. The majority of the neutralizing antibodies target the gHgL subunit. The non-neutralizing antibodies predominantly target the gB and pp65 proteins. Sequence analysis indicated that V160 induced a class of gHgL antibodies expressing the HV1-18/KV1-5 germline genes in multiple subjects. This study provides valuable insights into primary targets for anti-HCMV antibodies induced by V160 vaccination.
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spelling pubmed-81729292021-06-07 A conditionally replication-defective cytomegalovirus vaccine elicits potent and diverse functional monoclonal antibodies in a phase I clinical trial Li, Leike Freed, Daniel C. Liu, Yaping Li, Fengsheng Barrett, Diane F. Xiong, Wei Ye, Xiaohua Adler, Stuart P. Rupp, Richard E. Wang, Dai Zhang, Ningyan Fu, Tong-Ming An, Zhiqiang NPJ Vaccines Article A conditionally replication-defective human cytomegalovirus (HCMV) vaccine, V160, was shown to be safe and immunogenic in a two-part, double-blind, randomized, placebo-controlled phase I clinical trial (NCT01986010). However, the specificities and functional properties of V160-elicited antibodies remain undefined. Here, we characterized 272 monoclonal antibodies (mAbs) isolated from single memory B cells of six V160-vaccinated subjects. The mAbs bind to diverse HCMV antigens, including multiple components of the pentamer, gB, and tegument proteins. The most-potent neutralizing antibodies target the pentamer-UL subunits. The binding sites of the antibodies overlap with those of antibodies responding to natural HCMV infection. The majority of the neutralizing antibodies target the gHgL subunit. The non-neutralizing antibodies predominantly target the gB and pp65 proteins. Sequence analysis indicated that V160 induced a class of gHgL antibodies expressing the HV1-18/KV1-5 germline genes in multiple subjects. This study provides valuable insights into primary targets for anti-HCMV antibodies induced by V160 vaccination. Nature Publishing Group UK 2021-06-02 /pmc/articles/PMC8172929/ /pubmed/34078915 http://dx.doi.org/10.1038/s41541-021-00342-3 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Li, Leike
Freed, Daniel C.
Liu, Yaping
Li, Fengsheng
Barrett, Diane F.
Xiong, Wei
Ye, Xiaohua
Adler, Stuart P.
Rupp, Richard E.
Wang, Dai
Zhang, Ningyan
Fu, Tong-Ming
An, Zhiqiang
A conditionally replication-defective cytomegalovirus vaccine elicits potent and diverse functional monoclonal antibodies in a phase I clinical trial
title A conditionally replication-defective cytomegalovirus vaccine elicits potent and diverse functional monoclonal antibodies in a phase I clinical trial
title_full A conditionally replication-defective cytomegalovirus vaccine elicits potent and diverse functional monoclonal antibodies in a phase I clinical trial
title_fullStr A conditionally replication-defective cytomegalovirus vaccine elicits potent and diverse functional monoclonal antibodies in a phase I clinical trial
title_full_unstemmed A conditionally replication-defective cytomegalovirus vaccine elicits potent and diverse functional monoclonal antibodies in a phase I clinical trial
title_short A conditionally replication-defective cytomegalovirus vaccine elicits potent and diverse functional monoclonal antibodies in a phase I clinical trial
title_sort conditionally replication-defective cytomegalovirus vaccine elicits potent and diverse functional monoclonal antibodies in a phase i clinical trial
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172929/
https://www.ncbi.nlm.nih.gov/pubmed/34078915
http://dx.doi.org/10.1038/s41541-021-00342-3
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