Immunity and Protective Efficacy of a Plant-Based Tobacco Mosaic Virus-like Nanoparticle Vaccine against Influenza a Virus in Mice.

IF 5.2 3区医学 Q1 IMMUNOLOGY

Vaccines Pub Date : 2024-09-26 DOI:10.3390/vaccines12101100

Adthakorn Madapong, Erika M Petro-Turnquist, Richard J Webby, Alison A McCormick, Eric A Weaver

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Abstract

Background: The rapid production of influenza vaccines is crucial to meet increasing pandemic response demands. Here, we developed plant-made vaccines comprising centralized consensus influenza hemagglutinin (HA-con) proteins (H1 and H3 subtypes) conjugated to a modified plant virus, tobacco mosaic virus (TMV) nanoparticle (TMV-HA-con).

Methods: We compared immune responses and protective efficacy against historical H1 or H3 influenza A virus infections among TMV-HA-con, HA-con protein combined with AddaVax™ adjuvant, and whole-inactivated virus vaccine (Fluzone^®).

Results: Immunogenicity studies demonstrated robust IgG, IgM, and IgA responses in the TMV-HA-con and HA-con protein vaccinated groups, with relatively low induction of interferon (IFN)-γ⁺ T-cell responses across all vaccinated groups. The TMV-HA-con and HA-con protein groups displayed partial protection (100% and 80% survival) with minimal weight loss following challenge with two H1N1 strains. The HA-con protein group exhibited 80% and 100% survival against two H3 strains, whereas the TMV-HA-con groups showed reduced protection (20% survival). The Fluzone^® group conferred 20-100% survival against two H1N1 strains and one H3N1 strain, but did not protect against H3N2 infection.

Conclusions: Our findings indicate that TMV-HA and HA-con protein vaccines with adjuvant induce protective immune responses against influenza A virus infections. Furthermore, our results underscore the potential of plant-based production using TMV-like nanoparticles for developing influenza A virus candidate vaccines.

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基于植物的烟草花叶病毒样纳米粒子疫苗对小鼠甲型流感病毒的免疫力和保护效力

背景：快速生产流感疫苗对于满足日益增长的大流行病应对需求至关重要。在此，我们开发了由集中共识流感血凝素（HA-con）蛋白（H1 和 H3 亚型）与改良植物病毒--烟草花叶病毒（TMV）纳米颗粒（TMV-HA-con）共轭的植物制成的疫苗：我们比较了 TMV-HA-con、HA-con 蛋白结合 AddaVax™ 佐剂和全灭活病毒疫苗（Fluzone®）对历史上 H1 或 H3 甲型流感病毒感染的免疫反应和保护效力：免疫原性研究表明，TMV-HA-con 和 HA-con 蛋白疫苗接种组的 IgG、IgM 和 IgA 反应较强，而所有疫苗接种组诱导的干扰素 (IFN)-γ+ T 细胞反应相对较低。TMV-HA-con组和HA-con蛋白组在两种H1N1病毒株的挑战下表现出部分保护（存活率分别为100%和80%），体重下降极少。HA-con蛋白组对两种H3毒株的存活率分别为80%和100%，而TMV-HA-con组的保护能力较弱（存活率为20%）。Fluzone® 组对两种 H1N1 菌株和一种 H3N1 菌株的存活率为 20%-100%，但对 H3N2 感染没有保护作用：我们的研究结果表明，含佐剂的 TMV-HA 和 HA-con 蛋白疫苗可诱导针对甲型流感病毒感染的保护性免疫反应。此外，我们的研究结果还强调了基于植物生产的 TMV 类纳米颗粒在开发甲型流感病毒候选疫苗方面的潜力。

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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.