Academic Journal
2772. HCMV gB Ectodomain Subunit and gB mRNA Vaccines Reduce AD-3 Immunodominance and Elicit More Durable Antibody Responses Than gB/MF59 Immunization
| Title: | 2772. HCMV gB Ectodomain Subunit and gB mRNA Vaccines Reduce AD-3 Immunodominance and Elicit More Durable Antibody Responses Than gB/MF59 Immunization |
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| Authors: | Nelson, Cody S, Jenks, Jennifer A, Pardi, Norbert, Roark, Hunter K, Goodwin, Matthew, Weissman, Drew, Permar, Sallie R |
| Publisher Information: | Oxford University Press |
| Publication Year: | 2019 |
| Collection: | PubMed Central (PMC) |
| Subject Terms: | Abstracts |
| Description: | BACKGROUND: A vaccine to prevent maternal acquisition of human cytomegalovirus (HCMV) during pregnancy is one potential strategy to reduce the incidence of congenital disease. The MF59-adjuvanted glycoprotein B (gB/MF59) protein subunit vaccine is the most efficacious tested to-date, though achieved only 50% efficacy in phase 2 trial. We previously identified that gB/MF59 vaccination elicited poor heterologous virus neutralization and an immunodominant response against non-neutralizing/cytosolic antigenic domain 3 (AD-3) (Figure 1). Thus, we sought novel gB vaccination strategies to improve functional antibody responses and reduce AD-3 immunodominance. METHODS: Groups of juvenile New Zealand White rabbits (n = 6) were administered 3 sequential doses of gB protein with an MF59-like squalene adjuvant IM, gB ectodomain protein (lacking AD-3) + squalene adjuvant IM, or lipid nanoparticle (LNP)-packaged nucleoside-modified mRNA encoding gB ID. RESULTS: The AD-3 immunodominant IgG response seen in human vaccinees was closely mimicked in rabbits, with 78% of binding antibodies directed against this region in the gB protein group compared with 1% and 46% in the ectodomain and mRNA-LNP-vaccinated groups respectively (Figure 2). All vaccines were highly immunogenic with similar kinetics and comparable peak gB-binding/functional antibody responses. However, both ectodomain and mRNA-LNP-immunized rabbits exhibited enhanced durability of IgG binding to gB protein (P = 0.04 and 0.02, respectively), and the mRNA-LNP group had more durable binding of cell membrane-associated gB (P < 0.001) (Figure 3). Additionally, ectodomain and mRNA-LNP-vaccinated rabbits had increased durability of antibodies targeting neutralizing epitopes AD-4 and AD-5 (P < 0.01). Finally, low-magnitude gB-specific T-cell activity was observed in the gB protein and mRNA-LNP groups, though not in ectodomain-vaccinated rabbits. CONCLUSION: Altogether these data suggest that gB ectodomain subunit and gB mRNA-LNP vaccine formulations reduced targeting of ... |
| Document Type: | text |
| Language: | English |
| Relation: | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6810577/; http://dx.doi.org/10.1093/ofid/ofz360.2449 |
| DOI: | 10.1093/ofid/ofz360.2449 |
| Availability: | https://doi.org/10.1093/ofid/ofz360.2449 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6810577/ |
| Rights: | © The Author(s) 2019. Published by Oxford University Press on behalf of Infectious Diseases Society of America. ; http://creativecommons.org/licenses/by-nc-nd/4.0/ ; This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
| Accession Number: | edsbas.202B11A |
| Database: | BASE |
| Description not available. |