English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

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 non-neutralizing epitope AD-3 and elicited more durable IgG responses than gB protein vaccination. These next-generation HCMV vaccine candidates aiming to improve upon the partial efficacy of gB/MF59 vaccination should be further evaluated in preclinical models. Disclosures All authors: No reported disclosures.

2772. HCMV gB Ectodomain Subunit and gB mRNA Vaccines Reduce AD-3 Immunodominance and Elicit More Durable Antibody Responses Than gB/MF59 Immunization