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A three antigen hepatitis B vaccine induces T cells to Pres1 and Pres2 which correlate with anti HBs antibody titers: An investigation into the immunological mechanisms contributing to high anti-HBs titers
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A three antigen hepatitis B vaccine induces T cells to Pres1 and Pres2 which correlate with anti HBs antibody titers: An investigation into the immunological mechanisms contributing to high anti-HBs titers
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Journal Article
A three antigen hepatitis B vaccine induces T cells to Pres1 and Pres2 which correlate with anti HBs antibody titers: An investigation into the immunological mechanisms contributing to high anti-HBs titers
2025
Overview
PreHevbrio® is a 3-antigen HBV vaccine (3-A-HBV) engineered to express the three HBV envelope proteins; the small ‘S' hepatitis B surface antigen (SHBs or HBsAg), the middle pre-S2 + HBsAg (MHBs) and the large PreS1 + PreS2 + HBsAg (LHBs) antigens. 3-A-HBV has been shown to induce superior and more durable antibody responses relative to a 1-A-HBV despite containing half the ‘S' antigen dose. To explain the mechanism(s) behind the high immunogenicity, the potential influence of mammalian glycosylation, HBs antigen conformation, anti-HBs epitope binding profiles and T-cell responses to the PreS antigens were investigated.
In this paper, we demonstrate that glycosylation status does not play a role in the increased immunogenicity of the 3-A-HBV, but that the 3-A-HBV particles are able to induce T cell responses to PreS1 and PreS2 antigens. Epitope mapping demonstrated that the 3-A-HBV particles are inherently more antigenic than 1-A-HBV particles, leading to quantitative differences in the anti-HBs antibody response. Further, we demonstrate that the T cell responses significantly correlate with the higher observed anti-HBs titers and may contribute to the higher and more durable anti-HBs titers.
This trial is registered at Clinicaltrials.gov (NCT03393754) and EudraCT (2017–001819-36).
•PreHevbrio is a 3-antigen HBV vaccine shown to induce high anti-HBs titers following vaccination.•Immunological aspects of 3-A-HBV were studied to reveal the mechanisms behind the immunogenicity.•Epitope mapping revealed that 3-A-HBV particles are more antigenic than 1-A-HBV particles.•T cell responses may contribute to the higher and more durable anti-HBs titers.
Publisher
Elsevier Ltd,Elsevier Limited
Subject
/ Antigens
/ Consent
/ Engerix
/ epitopes
/ Female
/ Hepatitis B - prevention & control
/ Hepatitis B Antibodies - blood
/ Hepatitis B Antibodies - immunology
/ Hepatitis B Surface Antigens - immunology
/ Hepatitis B Vaccines - administration & dosage
/ Hepatitis B Vaccines - immunology
/ Hepatitis B virus - immunology
/ Humans
/ Male
/ mammals
/ Peptides
/ Protein Precursors - immunology
/ Vaccine
/ Vaccines
