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

Abstract 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 anti...

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Autores principales:	Leike Li, Daniel C. Freed, Yaping Liu, Fengsheng Li, Diane F. Barrett, Wei Xiong, Xiaohua Ye, Stuart P. Adler, Richard E. Rupp, Dai Wang, Ningyan Zhang, Tong-Ming Fu, Zhiqiang An
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/8407aee0085d434d8f8d2b457a78ae7d
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spelling	oai:doaj.org-article:8407aee0085d434d8f8d2b457a78ae7d2021-12-02T17:50:41ZA conditionally replication-defective cytomegalovirus vaccine elicits potent and diverse functional monoclonal antibodies in a phase I clinical trial10.1038/s41541-021-00342-32059-0105https://doaj.org/article/8407aee0085d434d8f8d2b457a78ae7d2021-06-01T00:00:00Zhttps://doi.org/10.1038/s41541-021-00342-3https://doaj.org/toc/2059-0105Abstract 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.Leike LiDaniel C. FreedYaping LiuFengsheng LiDiane F. BarrettWei XiongXiaohua YeStuart P. AdlerRichard E. RuppDai WangNingyan ZhangTong-Ming FuZhiqiang AnNature PortfolioarticleImmunologic diseases. AllergyRC581-607Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Vaccines, Vol 6, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Leike Li Daniel C. Freed Yaping Liu Fengsheng Li Diane F. Barrett Wei Xiong Xiaohua Ye Stuart P. Adler Richard E. Rupp Dai Wang Ningyan Zhang Tong-Ming Fu Zhiqiang An A conditionally replication-defective cytomegalovirus vaccine elicits potent and diverse functional monoclonal antibodies in a phase I clinical trial
description	Abstract 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.
format	article
author	Leike Li Daniel C. Freed Yaping Liu Fengsheng Li Diane F. Barrett Wei Xiong Xiaohua Ye Stuart P. Adler Richard E. Rupp Dai Wang Ningyan Zhang Tong-Ming Fu Zhiqiang An
author_facet	Leike Li Daniel C. Freed Yaping Liu Fengsheng Li Diane F. Barrett Wei Xiong Xiaohua Ye Stuart P. Adler Richard E. Rupp Dai Wang Ningyan Zhang Tong-Ming Fu Zhiqiang An
author_sort	Leike Li
title	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_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_sort	conditionally replication-defective cytomegalovirus vaccine elicits potent and diverse functional monoclonal antibodies in a phase i clinical trial
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/8407aee0085d434d8f8d2b457a78ae7d
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A conditionally replication-defective cytomegalovirus vaccine elicits potent and diverse functional monoclonal antibodies in a phase I clinical trial

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