Intranasal Prime-Boost with Spike Vectors Generates Antibody and T-Cell Responses at the Site of SARS-CoV-2 Infection.

IF 5.2 3区 医学 Q1 IMMUNOLOGY
Vaccines Pub Date : 2024-10-18 DOI:10.3390/vaccines12101191
Muriel Metko, Jason Tonne, Alexa Veliz Rios, Jill Thompson, Haley Mudrick, David Masopust, Rosa Maria Diaz, Michael A Barry, Richard G Vile
{"title":"Intranasal Prime-Boost with Spike Vectors Generates Antibody and T-Cell Responses at the Site of SARS-CoV-2 Infection.","authors":"Muriel Metko, Jason Tonne, Alexa Veliz Rios, Jill Thompson, Haley Mudrick, David Masopust, Rosa Maria Diaz, Michael A Barry, Richard G Vile","doi":"10.3390/vaccines12101191","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Long-lived, re-activatable immunity to SARS-CoV-2 and its emerging variants will rely on T cells recognizing conserved regions of viral proteins across strains. Heterologous prime-boost regimens can elicit elevated levels of circulating CD8+ T cells that provide a reservoir of first responders upon viral infection. Although most vaccines are currently delivered intramuscularly (IM), the initial site of infection is the nasal cavity.</p><p><strong>Methods: </strong>Here, we tested the hypothesis that a heterologous prime and boost vaccine regimen delivered intranasally (IN) will generate improved immune responses locally at the site of virus infection compared to intramuscular vaccine/booster regimens.</p><p><strong>Results: </strong>In a transgenic human ACE2 murine model, both a Spike-expressing single-cycle adenovirus (SC-Ad) and an IFNß safety-enhanced replication-competent Vesicular Stomatitis Virus (VSV) platform generated anti-Spike antibody and T-cell responses that diminished with age. Although SC-Ad-Spike boosted a prime with VSV-Spike-mIFNß, SC-Ad-Spike alone induced maximal levels of IgG, IgA, and CD8+ T-cell responses.</p><p><strong>Conclusions: </strong>There were significant differences in T-cell responses in spleens compared to lungs, and the intranasal boost was significantly superior to the intramuscular boost in generating sentinel immune effectors at the site of the virus encounter in the lungs. These data show that serious consideration should be given to intranasal boosting with anti-SARS-CoV-2 vaccines.</p>","PeriodicalId":23634,"journal":{"name":"Vaccines","volume":"12 10","pages":""},"PeriodicalIF":5.2000,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11511174/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Vaccines","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3390/vaccines12101191","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Background: Long-lived, re-activatable immunity to SARS-CoV-2 and its emerging variants will rely on T cells recognizing conserved regions of viral proteins across strains. Heterologous prime-boost regimens can elicit elevated levels of circulating CD8+ T cells that provide a reservoir of first responders upon viral infection. Although most vaccines are currently delivered intramuscularly (IM), the initial site of infection is the nasal cavity.

Methods: Here, we tested the hypothesis that a heterologous prime and boost vaccine regimen delivered intranasally (IN) will generate improved immune responses locally at the site of virus infection compared to intramuscular vaccine/booster regimens.

Results: In a transgenic human ACE2 murine model, both a Spike-expressing single-cycle adenovirus (SC-Ad) and an IFNß safety-enhanced replication-competent Vesicular Stomatitis Virus (VSV) platform generated anti-Spike antibody and T-cell responses that diminished with age. Although SC-Ad-Spike boosted a prime with VSV-Spike-mIFNß, SC-Ad-Spike alone induced maximal levels of IgG, IgA, and CD8+ T-cell responses.

Conclusions: There were significant differences in T-cell responses in spleens compared to lungs, and the intranasal boost was significantly superior to the intramuscular boost in generating sentinel immune effectors at the site of the virus encounter in the lungs. These data show that serious consideration should be given to intranasal boosting with anti-SARS-CoV-2 vaccines.

用尖峰载体进行鼻内原液强化可在 SARS-CoV-2 感染部位产生抗体和 T 细胞应答。
背景:对 SARS-CoV-2 及其新变种的长效、可再激活免疫力将依赖于 T 细胞识别不同毒株病毒蛋白的保守区域。异源原代增强方案可引起循环 CD8+ T 细胞水平升高,从而在病毒感染时提供第一反应库。尽管目前大多数疫苗都是肌肉注射(IM),但最初的感染部位是鼻腔。方法:在此,我们测试了一个假设,即与肌肉注射疫苗/加强方案相比,鼻腔内注射异源原代和加强疫苗方案将在病毒感染部位产生更好的免疫反应:结果:在转基因人类 ACE2 小鼠模型中,表达 Spike 的单周期腺病毒(SC-Ad)和 IFNß 安全增强型复制能力强的水泡性口炎病毒(VSV)平台都能产生抗 Spike 抗体和 T 细胞应答,但这些应答会随着年龄的增长而减弱。尽管SC-Ad-Spike增强了VSV-Spike-mIFNß,但SC-Ad-Spike单独诱导的IgG、IgA和CD8+ T细胞应答水平最高:结论:脾脏与肺部的 T 细胞反应存在明显差异,在肺部病毒感染部位产生哨点免疫效应因子方面,鼻内强化明显优于肌肉注射强化。这些数据表明,应认真考虑用抗 SARS-CoV-2 疫苗进行鼻内增强。
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
Vaccines
Vaccines Pharmacology, Toxicology and Pharmaceutics-Pharmacology
CiteScore
8.90
自引率
16.70%
发文量
1853
审稿时长
18.06 days
期刊介绍: Vaccines (ISSN 2076-393X) is an international, peer-reviewed open access journal focused on laboratory and clinical vaccine research, utilization and immunization. Vaccines publishes high quality reviews, regular research papers, communications and case reports.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信