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鼻内加强免疫在小鼠中诱导针对严重急性呼吸综合征冠状病毒2的持久黏膜免疫。

Intranasal booster induces durable mucosal immunity against SARS-CoV-2 in mice.

作者信息

Koolaparambil Mukesh Reshma, Hill Tom, Kaiser Franziska, Prado-Smith Jessica, Schulz Jonathan E, Gallogly Shane, Herbold Lisa, Bauer Kaitlyn, Smith Brian J, Myers Lara, Carmody Aaron B, Shaia Carl, Munster Vincent J, van Doremalen Neeltje

机构信息

Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 S 4th street, Hamilton, MT, USA.

Integrated Data Science Section, Research Technology Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

出版信息

Sci Rep. 2025 Jul 7;15(1):24224. doi: 10.1038/s41598-025-06880-3.


DOI:10.1038/s41598-025-06880-3
PMID:40624061
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12234998/
Abstract

Vaccines against coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are highly effective in preventing severe disease but are less consistent in protecting against infection and transmission. Developing vaccines with enhanced immunogenicity that can provide protection in both the upper and lower respiratory tract (URT and LRT) is crucial. Mucosal immunization induces immunity at the site of initial infection, the respiratory tract, thereby preventing or mitigating infection. Here, we compared immune responses elicited by intramuscular mRNA vaccination alone with those elicited by intramuscular mRNA vaccination followed by intranasal administration of ChAdOx1 nCoV-19 vaccine in mice. Although both vaccination strategies induced strong systemic immunity, robust humoral and cellular mucosal immune responses, including spike-specific IgA and tissue-resident T cells, were only detected upon mucosal vaccination. Compared to unvaccinated animals, mucosal vaccination resulted in migration of T cells and macrophages into the nasal turbinates, as well as migration and proliferation of B and T cells in the nasal-associated lymphoid tissue. While both vaccination regimens provided protection across the entire respiratory tract at 2 weeks post-vaccination, at 12 weeks post-vaccination, only the mice that received a mucosal vaccination remained protected in the URT. Gene-expression profiling of the respiratory tract at 2 days post-infection revealed distinct clustering between groups. Enrichment of immune signaling pathways, including B and T cells receptor pathways, was significantly higher in intranasally vaccinated animals. Together, our study demonstrates that mucosal vaccination provides durable protection against SARS-CoV-2 than intramuscular vaccination alone.

摘要

针对由严重急性呼吸综合征冠状病毒2(SARS-CoV-2)引起的2019冠状病毒病(COVID-19)的疫苗,在预防重症方面非常有效,但在预防感染和传播方面的效果不太稳定。开发具有增强免疫原性、能在上呼吸道和下呼吸道(URT和LRT)均提供保护的疫苗至关重要。黏膜免疫可在初始感染部位即呼吸道诱导免疫,从而预防或减轻感染。在此,我们比较了单独肌肉注射mRNA疫苗与先肌肉注射mRNA疫苗再鼻内给予ChAdOx1 nCoV-19疫苗在小鼠中引发的免疫反应。虽然两种疫苗接种策略均诱导了强烈的全身免疫,但只有在进行黏膜疫苗接种后才检测到强大的体液和细胞黏膜免疫反应,包括刺突特异性IgA和组织驻留T细胞。与未接种疫苗的动物相比,黏膜疫苗接种导致T细胞和巨噬细胞迁移至鼻甲,以及B细胞和T细胞在鼻相关淋巴组织中迁移和增殖。虽然两种疫苗接种方案在接种后2周均能为整个呼吸道提供保护,但在接种后12周,只有接受黏膜疫苗接种的小鼠在上呼吸道仍受到保护。感染后2天对呼吸道进行基因表达谱分析显示,各组之间存在明显的聚类。鼻内接种疫苗的动物中,包括B细胞和T细胞受体途径在内的免疫信号通路的富集程度显著更高。总之,我们的研究表明,与单独肌肉注射疫苗相比,黏膜疫苗接种能为SARS-CoV-2提供更持久的保护。

相似文献

[1]
Intranasal booster induces durable mucosal immunity against SARS-CoV-2 in mice.

Sci Rep. 2025-7-7

[2]
Effective cellular and neutralizing immunity against SARS-CoV-2 after mRNA booster vaccination is associated with pDC and B cell activation.

Front Immunol. 2025-5-12

[3]
Intranasal replicon SARS-CoV-2 vaccine produces protective respiratory and systemic immunity and prevents viral transmission.

Mol Ther. 2025-7-2

[4]
COVID-19 mRNA Vaccines Induce Robust Levels of IgG but Limited Amounts of IgA Within the Oronasopharynx of Young Children.

J Infect Dis. 2024-12-16

[5]
Repeated COVID-19 mRNA-based vaccination contributes to SARS-CoV-2 neutralizing antibody responses in the mucosa.

Sci Transl Med. 2024-10-23

[6]
Establishment of human post-vaccination SARS-CoV-2 standard reference sera.

J Immunol Methods. 2024-7

[7]
Induction of lung mucosal immunity by a next-generation inhaled aerosol COVID-19 vaccine: an open-label, multi-arm phase 1 clinical trial.

Nat Commun. 2025-7-2

[8]
Humoral and Cellular Immune Responses to SARS-CoV-2 in Participants with Head and Neck Cancer.

Viruses. 2025-6-13

[9]
Monoclonal antibodies against the spike protein alter the endogenous humoral response to SARS-CoV-2 vaccination and infection.

Sci Transl Med. 2024-11-6

[10]
Targeting heptad repeats and fusion peptide: nanoparticle vaccine elicits mucosal immune response against SARS-CoV-2 variants.

J Nanobiotechnology. 2025-7-3

本文引用的文献

[1]
Adjuvanted subunit intranasal vaccine reduces SARS-CoV-2 onward transmission in hamsters.

Front Immunol. 2025-2-7

[2]
Evolving antibody response to SARS-CoV-2 antigenic shift from XBB to JN.1.

Nature. 2025-1

[3]
SARS-CoV-2 XBB.1.5 mRNA booster vaccination elicits limited mucosal immunity.

Sci Transl Med. 2024-10-23

[4]
Mucosal adenovirus vaccine boosting elicits IgA and durably prevents XBB.1.16 infection in nonhuman primates.

Nat Immunol. 2024-10

[5]
Mucosal immunization with ChAd-SARS-CoV-2-S prevents sequential transmission of SARS-CoV-2 to unvaccinated hamsters.

Sci Adv. 2024-8-2

[6]
Multi-antigen intranasal vaccine protects against challenge with sarbecoviruses and prevents transmission in hamsters.

Nat Commun. 2024-7-23

[7]
Antibody longevity and waning following COVID-19 vaccination in a 1-year longitudinal cohort in Bangladesh.

Sci Rep. 2024-5-20

[8]
Mucosal vaccine-induced cross-reactive CD8 T cells protect against SARS-CoV-2 XBB.1.5 respiratory tract infection.

Nat Immunol. 2024-3

[9]
Mucosal boosting enhances vaccine protection against SARS-CoV-2 in macaques.

Nature. 2024-2

[10]
Variable neutralizing antibody responses to 10 SARS-CoV-2 variants in natural infection with wild- type (B.1) virus, Kappa (B.1.617.1), and Delta (B.1.617.2) variants and COVISHIELD vaccine immunization in India: utility of the MSD platform.

Front Immunol. 2023

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