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大 HBs 抗原乙型肝炎疫苗对乙型肝炎病毒疫苗逃逸突变的中和作用。

Neutralization of hepatitis B virus with vaccine-escape mutations by hepatitis B vaccine with large-HBs antigen.

机构信息

Center for the Evolutionary Origins of Human Behavior, Kyoto University, Aichi, Japan.

Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan.

出版信息

Nat Commun. 2022 Sep 5;13(1):5207. doi: 10.1038/s41467-022-32910-z.

DOI:10.1038/s41467-022-32910-z
PMID:36064848
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9441830/
Abstract

Although the current hepatitis B (HB) vaccine comprising small-HBs antigen (Ag) is potent and safe, attenuated prophylaxis against hepatitis B virus (HBV) with vaccine-escape mutations (VEMs) has been reported. We investigate an HB vaccine consisting of large-HBsAg that overcomes the shortcomings of the current HB vaccine. Yeast-derived large-HBsAg is immunized into rhesus macaques, and the neutralizing activities of the induced antibodies are compared with those of the current HB vaccine. Although the antibodies induced by the current HB vaccine cannot prevent HBV infection with VEMs, the large-HBsAg vaccine-induced antibodies neutralize those infections. The HBV genotypes that exhibited attenuated neutralization via these vaccines are different. Here, we show that the HB vaccine consisting of large-HBsAg is useful to compensate for the shortcomings of the current HB vaccine. The combined use of these HB vaccines may induce antibodies that can neutralize HBV strains with VEMs or multiple HBV genotypes.

摘要

虽然目前包含小乙型肝炎表面抗原 (Ag) 的乙型肝炎 (HB) 疫苗具有强大且安全的功效，但已报告称，疫苗逃逸突变 (VEMs) 会削弱对乙型肝炎病毒 (HBV) 的预防作用。我们研究了一种由大乙型肝炎表面抗原组成的 HB 疫苗，以克服目前 HB 疫苗的缺点。酵母衍生的大乙型肝炎表面抗原被免疫接种到恒河猴中，并比较诱导的抗体的中和活性与目前的 HB 疫苗。虽然目前 HB 疫苗诱导的抗体不能预防具有 VEMs 的 HBV 感染，但大乙型肝炎表面抗原疫苗诱导的抗体可以中和这些感染。通过这些疫苗表现出减弱中和作用的 HBV 基因型不同。在这里，我们表明由大乙型肝炎表面抗原组成的 HB 疫苗可用于弥补目前 HB 疫苗的不足。联合使用这些 HB 疫苗可能会诱导能够中和具有 VEMs 或多种 HBV 基因型的 HBV 株的抗体。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3740/9445002/1840394d2fe6/41467_2022_32910_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3740/9445002/6c0295274f4d/41467_2022_32910_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3740/9445002/bdfd1e97e012/41467_2022_32910_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3740/9445002/fd5a6ba2a3a9/41467_2022_32910_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3740/9445002/b65cf94512f2/41467_2022_32910_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3740/9445002/2ca2118589f5/41467_2022_32910_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3740/9445002/1840394d2fe6/41467_2022_32910_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3740/9445002/6c0295274f4d/41467_2022_32910_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3740/9445002/bdfd1e97e012/41467_2022_32910_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3740/9445002/fd5a6ba2a3a9/41467_2022_32910_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3740/9445002/b65cf94512f2/41467_2022_32910_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3740/9445002/2ca2118589f5/41467_2022_32910_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3740/9445002/1840394d2fe6/41467_2022_32910_Fig6_HTML.jpg

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