Welcome to the new version of CaltechAUTHORS. Login is currently restricted to library staff. If you notice any issues, please email coda@library.caltech.edu
Published August 16, 2017 | Published
Journal Article Open

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

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.

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.

Attached Files

Published - journal.pone.0183377.pdf

Files

journal.pone.0183377.pdf
Files (2.9 MB)
Name Size Download all
md5:7ba07b1804e47fe18ea59d17f1c01733
2.9 MB Preview Download

Additional details

Created:
August 19, 2023
Modified:
October 17, 2023