Systemic and Mucosal Immune Responses Induced by Adenoviral-Vectored Consensus H5 Influenza A Vaccines in Mice and Swine.

IF 5.2 3区医学 Q1 IMMUNOLOGY

Vaccines Pub Date : 2025-08-30 DOI:10.3390/vaccines13090928

Adthakorn Madapong, Joshua Wiggins, Jennifer DeBeauchamp, Richard J Webby, Eric A Weaver

{"title":"Systemic and Mucosal Immune Responses Induced by Adenoviral-Vectored Consensus H5 Influenza A Vaccines in Mice and Swine.","authors":"Adthakorn Madapong, Joshua Wiggins, Jennifer DeBeauchamp, Richard J Webby, Eric A Weaver","doi":"10.3390/vaccines13090928","DOIUrl":null,"url":null,"abstract":"Background/objectives: The continued evolution and cross-species transmission of clade 2.3.4.4b H5Nx highly pathogenic avian influenza (HPAI) viruses underscores the need for broadly protective vaccines in swine, a key intermediary host. This study aimed to evaluate systemic and mucosal immune responses elicited by adenoviral-vectored (Ad) vaccines encoding a centralized consensus hemagglutinin antigen (H5CC) in mice and swine.Methods: We constructed H5CC-based vaccines that were delivered using replication-defective (Ad5 and Ad6) and replication-competent (Ad28 and Ad48) human adenoviral vectors. Using a serotype-switched prime-boost strategy, vaccines were delivered intramuscularly (IM) or intranasally (IN) in mice and swine. We determined humoral, mucosal, and cell-mediated immune responses by hemagglutination inhibition (HI), microneutralization assay (MNA), ELISA, and IFN-γ ELISpot. Protective efficacy was evaluated by lethal H5N1 challenge in mice.Results: All vaccine strategies and routes induced significant levels of anti-H5 immunity. Ad5/Ad6 IM immunization elicited strong systemic IgG and MNA titers and robust T cell responses. IN delivery with Ad5/Ad6 induced superior mucosal IgA levels in lungs and nasal secretion. In swine, Ad5/Ad6 IM conferred the highest MNA titer and T cell responses, while the IN route enhanced mucosal IgA. The Ad28/Ad48 vaccines induced immunity in a similar pattern as compared to the Ad5/Ad6 strategy, but to a slightly lesser degree, in general. The commercial H1/H3 swine influenza vaccine failed to elicit cross-protective immunity. All H5CC vaccinated mice survived lethal H5N1 challenge without weight loss.Conclusions: Adenoviral-vectored H5CC vaccines elicit broad, cross-clade immunity with route-dependent immune profiles. IM vaccination is optimal for systemic and cellular responses, while IN delivery enhances mucosal immunity. These findings support the advancement of adenoviral platforms for influenza control in swine and pandemic preparedness.","PeriodicalId":23634,"journal":{"name":"Vaccines","volume":"13 9","pages":""},"PeriodicalIF":5.2000,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12474482/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Vaccines","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3390/vaccines13090928","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/objectives: The continued evolution and cross-species transmission of clade 2.3.4.4b H5Nx highly pathogenic avian influenza (HPAI) viruses underscores the need for broadly protective vaccines in swine, a key intermediary host. This study aimed to evaluate systemic and mucosal immune responses elicited by adenoviral-vectored (Ad) vaccines encoding a centralized consensus hemagglutinin antigen (H5CC) in mice and swine.

Methods: We constructed H5CC-based vaccines that were delivered using replication-defective (Ad5 and Ad6) and replication-competent (Ad28 and Ad48) human adenoviral vectors. Using a serotype-switched prime-boost strategy, vaccines were delivered intramuscularly (IM) or intranasally (IN) in mice and swine. We determined humoral, mucosal, and cell-mediated immune responses by hemagglutination inhibition (HI), microneutralization assay (MNA), ELISA, and IFN-γ ELISpot. Protective efficacy was evaluated by lethal H5N1 challenge in mice.

Results: All vaccine strategies and routes induced significant levels of anti-H5 immunity. Ad5/Ad6 IM immunization elicited strong systemic IgG and MNA titers and robust T cell responses. IN delivery with Ad5/Ad6 induced superior mucosal IgA levels in lungs and nasal secretion. In swine, Ad5/Ad6 IM conferred the highest MNA titer and T cell responses, while the IN route enhanced mucosal IgA. The Ad28/Ad48 vaccines induced immunity in a similar pattern as compared to the Ad5/Ad6 strategy, but to a slightly lesser degree, in general. The commercial H1/H3 swine influenza vaccine failed to elicit cross-protective immunity. All H5CC vaccinated mice survived lethal H5N1 challenge without weight loss.

Conclusions: Adenoviral-vectored H5CC vaccines elicit broad, cross-clade immunity with route-dependent immune profiles. IM vaccination is optimal for systemic and cellular responses, while IN delivery enhances mucosal immunity. These findings support the advancement of adenoviral platforms for influenza control in swine and pandemic preparedness.

查看原文本刊更多论文

腺病毒载体H5甲型流感疫苗诱导小鼠和猪的全身和粘膜免疫应答

背景/目的：2.3.4.4b支H5Nx高致病性禽流感（HPAI）病毒的持续进化和跨物种传播强调了对猪这一关键中间宿主广泛保护性疫苗的需求。本研究旨在评估编码集中一致血凝素抗原（H5CC）的腺病毒载体（Ad）疫苗在小鼠和猪身上引发的全身和粘膜免疫反应。方法：构建了以复制缺陷型（Ad5和Ad6）和复制能力型（Ad28和Ad48）人腺病毒载体为载体的h5cc疫苗。在小鼠和猪中，采用血清型转换的初强化策略，通过肌肉注射（IM）或鼻内注射（IN）给药。我们通过血凝抑制（HI）、微量中和试验（MNA）、ELISA和IFN-γ ELISpot测定体液、粘膜和细胞介导的免疫反应。通过小鼠致死性H5N1攻击来评估保护效果。结果：所有疫苗策略和途径均可诱导显著水平的抗h5免疫。Ad5/Ad6 IM免疫可引起较强的全身IgG和MNA滴度以及较强的T细胞应答。与Ad5/Ad6一起递送可诱导肺和鼻分泌物上粘膜IgA水平升高。在猪中，Ad5/Ad6 IM具有最高的MNA滴度和T细胞反应，而In途径增强了粘膜IgA。与Ad5/Ad6策略相比，Ad28/Ad48疫苗以类似的模式诱导免疫，但一般程度稍低。商业化的H1/H3猪流感疫苗未能引起交叉保护性免疫。所有接种了H5CC疫苗的小鼠在致命的H5N1攻击中存活，体重没有减轻。结论：腺病毒载体的H5CC疫苗引起广泛的、跨进化的免疫，具有途径依赖的免疫特征。IM疫苗接种对全身和细胞反应是最佳的，而IN的递送增强粘膜免疫。这些发现支持了腺病毒平台在猪流感控制和大流行防备方面的进步。

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 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.