Induction of pluripotent protective immunity following immunisation with a chimeric vaccine against human cytomegalovirus.

Based on the life-time cost to the health care system, the Institute of Medicine has assigned the highest priority for a vaccine to control human cytomegalovirus (HCMV) disease in transplant patients and new born babies. In spite of numerous attempts successful licensure of a HCMV vaccine formulatio...

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Main Authors: Jie Zhong, Michael Rist, Leanne Cooper, Corey Smith, Rajiv Khanna
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2008-09-01
Series:PLoS ONE
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18806877/?tool=EBI
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spelling doaj-4a50801b19ab478e87c03c2daf9fd5782021-06-19T05:06:51ZengPublic Library of Science (PLoS)PLoS ONE1932-62032008-09-0139e325610.1371/journal.pone.0003256Induction of pluripotent protective immunity following immunisation with a chimeric vaccine against human cytomegalovirus.Jie ZhongMichael RistLeanne CooperCorey SmithRajiv KhannaBased on the life-time cost to the health care system, the Institute of Medicine has assigned the highest priority for a vaccine to control human cytomegalovirus (HCMV) disease in transplant patients and new born babies. In spite of numerous attempts successful licensure of a HCMV vaccine formulation remains elusive. Here we have developed a novel chimeric vaccine strategy based on a replication-deficient adenovirus which encodes the extracellular domain of gB protein and multiple HLA class I & II-restricted CTL epitopes from HCMV as a contiguous polypeptide. Immunisation with this chimeric vaccine consistently generated strong HCMV-specific CD8(+) and CD4(+) T-cells which co-expressed IFN-gamma and TNF-alpha, while the humoral response induced by this vaccine showed strong virus neutralizing capacity. More importantly, immunization with adenoviral chimeric vaccine also afforded protection against challenge with recombinant vaccinia virus encoding HCMV antigens and this protection was associated with the induction of a pluripotent antigen-specific cellular and antibody response. Furthermore, in vitro stimulation with this adenoviral chimeric vaccine rapidly expanded multiple antigen-specific human CD8(+) and CD4(+) T-cells from healthy virus carriers. These studies demonstrate that the adenovirus chimeric HCMV vaccine provides an excellent platform for reconstituting protective immunity to prevent HCMV diseases in different clinical settings.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18806877/?tool=EBI
collection DOAJ
language English
format Article
sources DOAJ
author Jie Zhong
Michael Rist
Leanne Cooper
Corey Smith
Rajiv Khanna
spellingShingle Jie Zhong
Michael Rist
Leanne Cooper
Corey Smith
Rajiv Khanna
Induction of pluripotent protective immunity following immunisation with a chimeric vaccine against human cytomegalovirus.
PLoS ONE
author_facet Jie Zhong
Michael Rist
Leanne Cooper
Corey Smith
Rajiv Khanna
author_sort Jie Zhong
title Induction of pluripotent protective immunity following immunisation with a chimeric vaccine against human cytomegalovirus.
title_short Induction of pluripotent protective immunity following immunisation with a chimeric vaccine against human cytomegalovirus.
title_full Induction of pluripotent protective immunity following immunisation with a chimeric vaccine against human cytomegalovirus.
title_fullStr Induction of pluripotent protective immunity following immunisation with a chimeric vaccine against human cytomegalovirus.
title_full_unstemmed Induction of pluripotent protective immunity following immunisation with a chimeric vaccine against human cytomegalovirus.
title_sort induction of pluripotent protective immunity following immunisation with a chimeric vaccine against human cytomegalovirus.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2008-09-01
description Based on the life-time cost to the health care system, the Institute of Medicine has assigned the highest priority for a vaccine to control human cytomegalovirus (HCMV) disease in transplant patients and new born babies. In spite of numerous attempts successful licensure of a HCMV vaccine formulation remains elusive. Here we have developed a novel chimeric vaccine strategy based on a replication-deficient adenovirus which encodes the extracellular domain of gB protein and multiple HLA class I & II-restricted CTL epitopes from HCMV as a contiguous polypeptide. Immunisation with this chimeric vaccine consistently generated strong HCMV-specific CD8(+) and CD4(+) T-cells which co-expressed IFN-gamma and TNF-alpha, while the humoral response induced by this vaccine showed strong virus neutralizing capacity. More importantly, immunization with adenoviral chimeric vaccine also afforded protection against challenge with recombinant vaccinia virus encoding HCMV antigens and this protection was associated with the induction of a pluripotent antigen-specific cellular and antibody response. Furthermore, in vitro stimulation with this adenoviral chimeric vaccine rapidly expanded multiple antigen-specific human CD8(+) and CD4(+) T-cells from healthy virus carriers. These studies demonstrate that the adenovirus chimeric HCMV vaccine provides an excellent platform for reconstituting protective immunity to prevent HCMV diseases in different clinical settings.
url https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18806877/?tool=EBI
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