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Comparison of homologous and heterologous prime-boost vaccine approaches using Modified Vaccinia Ankara and soluble protein to induce neutralizing antibodies by the human cytomegalovirus pentamer complex in mice

Chiuppesi, Flavia and Wussow, Felix and Scharf, Louise and Contreras, Heidi and Gao, Han and Meng, Zhuo and Nguyen, Jenny and Barry, Peter A. and Bjorkman, Pamela J. and Diamond, Don J. (2017) Comparison of homologous and heterologous prime-boost vaccine approaches using Modified Vaccinia Ankara and soluble protein to induce neutralizing antibodies by the human cytomegalovirus pentamer complex in mice. PLoS ONE, 12 (8). Art. No. e0183377. ISSN 1932-6203. PMCID PMC5558987. https://resolver.caltech.edu/CaltechAUTHORS:20170821-153942123

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Abstract

Since neutralizing antibodies (NAb) targeting the human cytomegalovirus (HCMV) pentamer complex (PC) potently block HCMV host cell entry, anti-PC NAb induction is thought to be important for a vaccine formulation to prevent HCMV infection. By developing a vaccine strategy based on soluble PC protein and using a previously generated Modified Vaccinia Ankara vector co-expressing all five PC subunits (MVA-PC), we compared HCMV NAb induction by homologous immunization using prime-boost vaccine regimen employing only PC protein or MVA-PC and heterologous immunization using prime-boost combinations of PC protein and MVA-PC. Utilizing a recently isolated anti-PC NAb, we produced highly pure soluble PC protein that displayed conformational and linear neutralizing epitopes, interfered with HCMV entry, and was recognized by antibodies induced by HCMV during natural infection. Mice vaccinated by different immunization routes with the purified PC protein in combination with a clinically approved adjuvant formulation elicited high-titer and durable HCMV NAb. While MVA-PC and soluble PC protein either alone or in combination elicited robust HCMV NAb, significantly different potencies of these vaccine approaches were observed in dependence on immunization schedule. Using only two immunizations, vaccination with MVA-PC alone or prime-boost combinations of MVA-PC and PC protein was significantly more effective in stimulating HCMV NAb than immunization with PC protein alone. In contrast, with three immunizations, NAb induced by soluble PC protein either alone or combined with two boosts of MVA-PC increased to levels that exceeded NAb titer stimulated by MVA-PC alone. These results provide insights into the potency of soluble protein and MVA to elicit NAb by the HCMV PC via homologous and heterologous prime-boost immunization, which may contribute to develop clinically deployable vaccine strategies to prevent HCMV infection.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1371/journal.pone.0183377DOIArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5558987/PubMed CentralArticle
ORCID:
AuthorORCID
Bjorkman, Pamela J.0000-0002-2277-3990
Additional Information:© 2017 Chiuppesi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Received: July 7, 2017; Accepted: August 2, 2017; Published: August 16, 2017. Data Availability Statement: All relevant data are within the paper. This research was funded by U.S. Public Health Service grant R01 AI103960 and AI063356 to DJD and PAB. DJD was partially supported by CA077544 and CA181045. The COH Cancer Center is supported by CA033572. The authors have declared that no competing interests exist. We thank Drs. Thomas Shenk and Eain Murphy (Stanford University) for providing HCMV TB40/Ewt-GFP BAC. We would like to thank Aline Matsuo for her help in the submission. This research was funded by U.S. Public Health Service grant R01 AI103960 and AI063356 to DJD and PAB. DJD was partially supported by CA077544 and CA181045. Research reported in this publication included work performed in the Light Microscopy Digital Imaging Core at City of Hope supported by the National Cancer Institute of the National Institutes of Health under award number P30CA033572. The content of this work is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Author Contributions: Investigation: Flavia Chiuppesi, Felix Wussow, Louise Scharf, Heidi Contreras, Peter A. Barry, Pamela J. Bjorkman, Don J. Diamond. Methodology: Han Gao, Zhuo Meng, Jenny Nguyen.
Funders:
Funding AgencyGrant Number
NIHR01 AI103960
NIHR01 AI063356
NIHCA077544
NIHCA181045
NIHCA033572
Issue or Number:8
PubMed Central ID:PMC5558987
Record Number:CaltechAUTHORS:20170821-153942123
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20170821-153942123
Official Citation:Chiuppesi F, Wussow F, Scharf L, Contreras H, Gao H, Meng Z, et al. (2017) Comparison of homologous and heterologous prime-boost vaccine approaches using Modified Vaccinia Ankara and soluble protein to induce neutralizing antibodies by the human cytomegalovirus pentamer complex in mice. PLoS ONE 12(8): e0183377. https://doi.org/10.1371/journal.pone.0183377
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:80655
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:21 Aug 2017 22:55
Last Modified:05 Dec 2019 21:39

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