Characterization of humoral and cellular immunity induced by mRNA vaccines expressing norovirus VP1 proteins in mice and nonhuman primates.

IF 12 1区医学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Molecular Therapy Pub Date : 2025-09-12 DOI:10.1016/j.ymthe.2025.09.023

Jiajie Wei,Karin Bystol,Leah Alabanza,Shuhui Lim,Jamie Greig,Pooja Gopal,Judith M Reyes Ballista,Jennifer D Galli,Christopher Warren,Andrew Swartz,Courtney David,Uijin Jeong,Estibaliz Gonzalez-Fernandez,Lizzy Aurora DeWitt,Gwenny Go,Athena Lago,Scott Radcliffe,Corey D May Fulton,Pamela Shen,Arthur Fridman,John Gaspar,Amanda Pirrone,Zhiyun Wen,Gregory O'Donnell,Lauren Austin,David McKenney,Paula Krosky,Yaping Liu,Andrew J Bett,Lan Zhang

{"title":"Characterization of humoral and cellular immunity induced by mRNA vaccines expressing norovirus VP1 proteins in mice and nonhuman primates.","authors":"Jiajie Wei,Karin Bystol,Leah Alabanza,Shuhui Lim,Jamie Greig,Pooja Gopal,Judith M Reyes Ballista,Jennifer D Galli,Christopher Warren,Andrew Swartz,Courtney David,Uijin Jeong,Estibaliz Gonzalez-Fernandez,Lizzy Aurora DeWitt,Gwenny Go,Athena Lago,Scott Radcliffe,Corey D May Fulton,Pamela Shen,Arthur Fridman,John Gaspar,Amanda Pirrone,Zhiyun Wen,Gregory O'Donnell,Lauren Austin,David McKenney,Paula Krosky,Yaping Liu,Andrew J Bett,Lan Zhang","doi":"10.1016/j.ymthe.2025.09.023","DOIUrl":null,"url":null,"abstract":"Noroviruses are a leading cause of acute gastroenteritis across all age groups, associated with ∼18% of diarrheal disease globally. Infections span a broad clinical spectrum, ranging from asymptomatic and self-limiting illnesses to hospitalizations and deaths. No preventative vaccines or targeted therapies are currently available. In this study, we designed vaccine candidates containing mRNAs encoding norovirus VP1 proteins of genotypes GI.1, GII.2, GII.3, GII.4, and GII.6, and evaluated their immunogenicity in mice and nonhuman primates (NHPs). In mice, all five mRNAs, dosed separately or together, elicited serum IgG antibodies that bound to norovirus virus-like particles (VLPs), serum antibodies that blocked the binding of VLPs to histo-blood group antigens (HBGA), and norovirus-specific T cell responses. In NHPs, a pentavalent vaccine candidate induced strong humoral and cellular immune responses against each genotype included in the vaccine. Furthermore, compared to VLPs, mRNAs induced similar levels of humoral and cellular responses and comparable levels of durability, as measured by serum antibody titers. Our results indicate that a multivalent mRNA vaccine candidate encoding norovirus VP1 proteins is immunogenic in preclinical models and is a promising candidate to be evaluated in clinical trials.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":"24 1","pages":""},"PeriodicalIF":12.0000,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.ymthe.2025.09.023","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Noroviruses are a leading cause of acute gastroenteritis across all age groups, associated with ∼18% of diarrheal disease globally. Infections span a broad clinical spectrum, ranging from asymptomatic and self-limiting illnesses to hospitalizations and deaths. No preventative vaccines or targeted therapies are currently available. In this study, we designed vaccine candidates containing mRNAs encoding norovirus VP1 proteins of genotypes GI.1, GII.2, GII.3, GII.4, and GII.6, and evaluated their immunogenicity in mice and nonhuman primates (NHPs). In mice, all five mRNAs, dosed separately or together, elicited serum IgG antibodies that bound to norovirus virus-like particles (VLPs), serum antibodies that blocked the binding of VLPs to histo-blood group antigens (HBGA), and norovirus-specific T cell responses. In NHPs, a pentavalent vaccine candidate induced strong humoral and cellular immune responses against each genotype included in the vaccine. Furthermore, compared to VLPs, mRNAs induced similar levels of humoral and cellular responses and comparable levels of durability, as measured by serum antibody titers. Our results indicate that a multivalent mRNA vaccine candidate encoding norovirus VP1 proteins is immunogenic in preclinical models and is a promising candidate to be evaluated in clinical trials.

查看原文本刊更多论文

表达诺如病毒VP1蛋白的mRNA疫苗在小鼠和非人灵长类动物中诱导的体液和细胞免疫特性

诺如病毒是所有年龄组急性胃肠炎的主要原因，与全球约18%的腹泻病有关。感染跨越广泛的临床范围，从无症状和自限性疾病到住院和死亡。目前还没有预防性疫苗或靶向治疗方法。在这项研究中，我们设计了含有编码诺如病毒VP1基因型GI.1、GII.2、GII.3、GII.4和GII.6的mrna的候选疫苗，并评估了它们在小鼠和非人灵长类动物（NHPs）中的免疫原性。在小鼠实验中，所有5种mrna，单独或一起给药，都能引起血清中结合诺如病毒样颗粒（VLPs）的IgG抗体，阻断VLPs与组织血型抗原（HBGA）结合的血清抗体，以及诺如病毒特异性T细胞反应。在NHPs中，一种五价候选疫苗诱导了针对疫苗中每种基因型的强体液和细胞免疫反应。此外，通过血清抗体滴度测量，与VLPs相比，mrna诱导了相似水平的体液和细胞反应以及相当水平的持久性。我们的研究结果表明，一种编码诺如病毒VP1蛋白的多价mRNA候选疫苗在临床前模型中具有免疫原性，是一种有希望在临床试验中进行评估的候选疫苗。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Molecular Therapy 医学-生物工程与应用微生物

CiteScore

19.20

自引率

3.20%

发文量

357

审稿时长

3 months

期刊介绍： Molecular Therapy is the leading journal for research in gene transfer, vector development, stem cell manipulation, and therapeutic interventions. It covers a broad spectrum of topics including genetic and acquired disease correction, vaccine development, pre-clinical validation, safety/efficacy studies, and clinical trials. With a focus on advancing genetics, medicine, and biotechnology, Molecular Therapy publishes peer-reviewed research, reviews, and commentaries to showcase the latest advancements in the field. With an impressive impact factor of 12.4 in 2022, it continues to attract top-tier contributions.