三抗原乙型肝炎疫苗可诱导T细胞产生Pres1和Pres2，这与抗HBs抗体滴度相关：对导致高抗 HBs 滴度的免疫机制的研究。

IF 4.5 3区医学 Q2 IMMUNOLOGY

Vaccine Pub Date : 2024-11-12 DOI:10.1016/j.vaccine.2024.126513

Tamara K. Berthoud , Tanvir Ahmed , Warner Nadia , Illia Petrov , Lanjian Yang , Danni Colledge , Rachel Hammond , Catalina Soare , Barthelemy Ontsouka , Daniel Plaskin , David E. Anderson , Francisco Diaz-Mitoma

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引用次数: 0

摘要

PreHevbrio® 是一种三抗原乙型肝炎病毒疫苗（3-A-HBV），可表达三种乙型肝炎病毒包膜蛋白：小的 "S "乙型肝炎表面抗原（SHBs 或 HBsAg）、中间的前 S2 + HBsAg（MHBs）和大的 PreS1 + PreS2 + HBsAg（LHBs）抗原。尽管 3-A-HBV 的 "S "抗原剂量只有 1-A-HBV 的一半，但与 1-A-HBV 相比，3-A-HBV 可诱导更优越、更持久的抗体反应。为了解释高免疫原性背后的机制，我们研究了哺乳动物糖基化、HBs 抗原构象、抗 HBs 表位结合图谱和 T 细胞对 PreS 抗原反应的潜在影响。在本文中，我们证明糖基化状态对 3-A-HBV 免疫原性的增加不起作用，但 3-A-HBV 颗粒能诱导 T 细胞对 PreS1 和 PreS2 抗原产生反应。表位图谱显示，3-A-HBV 颗粒比 1-A-HBV 颗粒本身具有更强的抗原性，从而导致抗 HBs 抗体反应在数量上的差异。此外，我们还证明 T 细胞反应与观察到的较高抗 HBs 滴度明显相关，可能有助于获得更高和更持久的抗 HBs 滴度。该试验已在 Clinicaltrials.gov (NCT03393754) 和 EudraCT (2017-001819-36) 上注册。

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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

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).

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来源期刊

Vaccine 医学-免疫学

CiteScore

8.70

自引率

5.50%

发文量

992

审稿时长

131 days

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