LC16m8疫苗的免疫学分析：猴痘的临床前和早期临床见解

Immunological analysis of LC16m8 vaccine: preclinical and early clinical insights into mpox.

作者信息

Kobiyama Kouji, Utsumi Daichi, Kaku Yu, Sasaki Eita, Yasui Fumihiko, Okamura Tomotaka, Onodera Taishi, Tobuse Asuka Joy, Sakkour Areej, Amiry Ahmad Faisal, Hayashi Tomoya, Temizoz Burcu, Liu Kaiwen, Negishi Hideo, Toyama-Sorimachi Noriko, Kohara Michinori, Sawasaki Tatsuya, Takagi Junichi, Sato Kei, Takahashi Yoshimasa, Yasutomi Yasuhiro, Ishii Ken J

机构信息

Division of Vaccine Science, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan; International Vaccine Design Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.

Laboratory of Immunoregulation and Vaccine Research, Tsukuba Primate Research Center, National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki, Japan.

出版信息

EBioMedicine. 2025 May;115:105703. doi: 10.1016/j.ebiom.2025.105703. Epub 2025 Apr 15.

DOI:10.1016/j.ebiom.2025.105703

PMID:40239465

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12020844/

Abstract

BACKGROUND

The global mpox outbreak (2022-2024) highlights the need for effective and safe vaccines, particularly for vulnerable populations. The LC16m8 vaccine, an attenuated vaccinia virus strain for smallpox, shows promise in inducing immunity against the monkeypox virus (MPXV).

METHODS

We conducted a comprehensive immunological evaluation of LC16m8 in mice, non-human primates, and humans.

FINDINGS

LC16m8 induced strong humoural responses in BALB/c, C57BL/6J, and CAST/EiJ mice, targeting MPXV H3, A35, and M1R antigens, promoting germinal centre B cells and follicular helper T cells, essential for long-term immunity. Vaccinated CAST/EiJ mice showed reduced lung MPXV viral loads, demonstrating efficacy. In humans, LC16m8 enhanced neutralising antibodies against multiple MPXV clades, suggesting broad protection. In cynomolgus monkeys, systemic administration caused localised pox lesions without significantly affecting weight, temperature, or haematological parameters.

INTERPRETATION

This cross-species immunological analysis provides preclinical and early clinical insights into LC16m8's efficacy and safety against mpox. While LC16m8 enhanced antibody responses against MPXV clade Ia and Ib, further studies are required to evaluate its efficacy, particularly in naive and immunocompromised populations.

FUNDING

This research was supported by AMED under Grant Numbers JP243fa727002, JP243fa727001s0703, and JP243fa627001h0003 (K.J.I), JP24jf0126002, JP24fk0108690, JP243fa627001h0003, and JP243fa727002 (K.S), JP243fa727002 (Y.T.), JP243fa727002 and JP243fa627007h0003 (Y.Y.), and by the Research Support Project for Life Science and Drug Discovery (BINDS) from AMED under Grant Number JP23ama121011 (J.T.), and JP23ama121010 (T.S.), and by the Ministry of Education, Culture, Sports, Science and Technology in Japan under Grant Number 23K06577 (E.S.). AMED under Grant Number JP233fa827017 and JP243fa827017 (F.Y.), JP22fk0108501 (M.K.).

摘要

背景

2022 - 2024年全球猴痘疫情凸显了对有效且安全疫苗的需求，尤其是针对弱势群体。LC16m8疫苗是一种用于天花的减毒痘苗病毒株，在诱导抗猴痘病毒（MPXV）免疫方面显示出前景。

方法

我们在小鼠、非人灵长类动物和人类中对LC16m8进行了全面的免疫学评估。

研究结果

LC16m8在BALB/c、C57BL/6J和CAST/EiJ小鼠中诱导了强烈的体液免疫反应，靶向MPXV H3、A35和M1R抗原，促进生发中心B细胞和滤泡辅助性T细胞的产生，这些细胞对长期免疫至关重要。接种疫苗的CAST/EiJ小鼠肺部MPXV病毒载量降低，证明了其有效性。在人类中，LC16m8增强了针对多个MPXV分支的中和抗体，表明具有广泛的保护作用。在食蟹猴中，全身给药导致局部痘疹病变，但对体重、体温或血液学参数没有显著影响。

解读

这项跨物种免疫学分析为LC16m8针对猴痘的疗效和安全性提供了临床前和早期临床见解。虽然LC16m8增强了针对MPXV Ia和Ib分支的抗体反应，但仍需要进一步研究来评估其疗效，特别是在未感染过和免疫功能低下的人群中。

资金支持

本研究由日本厚生劳动省资助，资助编号分别为JP243fa727002、JP243fa727001s0703、JP243fa627001h0003（K.J.I）、JP24jf0126002、JP24fk0108690、JP243fa627001h0003、JP243fa727002（K.S）、JP243fa727002（Y.T.）、JP243fa727002和JP243fa627007h0003（Y.Y.）；由日本厚生劳动省的生命科学与药物发现研究支持项目（BINDS）资助，资助编号为JP23ama121011（J.T.）、JP23ama121010（T.S.）；由日本文部科学省资助，资助编号为23K06577（E.S.）。日本厚生劳动省资助编号为JP233fa827017和JP243fa827017（F.Y.）、JP22fk0108501（M.K.）。