Academic Journal
Human Cytomegalovirus Glycoprotein B Nucleoside-Modified mRNA Vaccine Elicits Antibody Responses with Greater Durability and Breadth than MF59-Adjuvanted gB Protein Immunization
| Title: | Human Cytomegalovirus Glycoprotein B Nucleoside-Modified mRNA Vaccine Elicits Antibody Responses with Greater Durability and Breadth than MF59-Adjuvanted gB Protein Immunization |
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| Authors: | Nelson, Cody S., Jenks, Jennifer A., Pardi, Norbert, Goodwin, Matthew, Roark, Hunter, Edwards, Whitney, McLellan, Jason S., Pollara, Justin, Weissman, Drew, Permar, Sallie R. |
| Superior Title: | J Virol |
| Publisher Information: | American Society for Microbiology |
| Publication Year: | 2020 |
| Collection: | PubMed Central (PMC) |
| Subject Terms: | Vaccines and Antiviral Agents |
| Description: | A vaccine to prevent maternal acquisition of human cytomegalovirus (HCMV) during pregnancy is a primary strategy to reduce the incidence of congenital disease. The MF59-adjuvanted glycoprotein B (gB) protein subunit vaccine (gB/MF59) is the most efficacious vaccine tested to date for this indication. We previously identified that gB/MF59 vaccination elicited poor neutralizing antibody responses and an immunodominant response against gB antigenic domain 3 (AD-3). Thus, we sought to test novel gB vaccines to improve functional antibody responses and reduce AD-3 immunodominance. Groups of juvenile New Zealand White rabbits were administered 3 sequential doses of the full-length gB protein with an MF59-like squalene-based adjuvant, the gB ectodomain protein (lacking AD-3) with squalene adjuvant, or lipid nanoparticle (LNP)-encapsulated nucleoside-modified mRNA encoding full-length gB. All vaccines were highly immunogenic with similar kinetics and comparable peak gB-binding and functional antibody responses. The AD-3-immunodominant IgG response following human gB/MF59 vaccination was closely mimicked in rabbits. Though gB ectodomain subunit vaccination eliminated targeting of epitopes in AD-3, it did not improve vaccine-elicited neutralizing or nonneutralizing antibody functions. gB nucleoside-modified mRNA-LNP-immunized rabbits exhibited an enhanced durability of vaccine-elicited antibody responses. Furthermore, the gB mRNA-LNP vaccine enhanced the breadth of IgG binding responses against discrete gB peptides. Finally, low-magnitude gB-specific T cell activity was observed in the full-length gB protein and mRNA-LNP groups, though not in ectodomain-vaccinated rabbits. Altogether, these data suggest that the use of gB nucleoside-modified mRNA-LNP vaccines is a viable strategy for improving on the partial efficacy of gB/MF59 vaccination and should be further evaluated in preclinical models. IMPORTANCE Human cytomegalovirus (HCMV) is the most common infectious cause of infant birth defects, resulting in permanent ... |
| Document Type: | text |
| Language: | English |
| Relation: | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7163130/; http://www.ncbi.nlm.nih.gov/pubmed/32051265; http://dx.doi.org/10.1128/JVI.00186-20 |
| DOI: | 10.1128/JVI.00186-20 |
| Availability: | https://doi.org/10.1128/JVI.00186-20 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7163130/ http://www.ncbi.nlm.nih.gov/pubmed/32051265 |
| Rights: | Copyright © 2020 American Society for Microbiology. ; https://doi.org/10.1128/ASMCopyrightv2 ; All Rights Reserved (https://doi.org/10.1128/ASMCopyrightv2) . |
| Accession Number: | edsbas.DEEE60E3 |
| Database: | BASE |
| Description not available. |