Evidence map›Paper›PMID 40338637›Full record

ArticleeLife2025

Comprehensive analysis of nasal IgA antibodies induced by intranasal administration of the SARS-CoV-2 spike protein.

Kentarou Waki, Hideki Tani, Eigo Kawahara, Yumiko Saga, Takahisa Shimada, Emiko Yamazaki, Seiichi Koike, Yoshitomo Morinaga, Masaharu Isobe, Nobuyuki Kurosawa

Abstract read
In one paragraph

Article in eLife, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Different Fc scaffolds enhance the breadth ofFrontiers in immunology · 2025
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Kentarou WakiLaboratory of Molecular and Cellular Biology, Graduate School of Science and Engineering for Education, University of Toyama, Toyama, Japan.
Hideki TaniDepartment of Virology, Toyama Institute of Health, Toyama, Japan.ORCID https://orcid.org/0000-0002-6309-277X
Eigo KawaharaDepartment of Microbiology, Toyama University Graduate School of Medicine and Pharmaceutical Sciences, Toyama, Japan.
Yumiko SagaDepartment of Virology, Toyama Institute of Health, Toyama, Japan.
Takahisa ShimadaDepartment of Virology, Toyama Institute of Health, Toyama, Japan.
Emiko YamazakiDepartment of Virology, Toyama Institute of Health, Toyama, Japan.
Seiichi KoikeLaboratory of Molecular and Cellular Biology, Graduate School of Innovative Life Science, University of Toyama, Toyama, Japan.ORCID https://orcid.org/0000-0001-8203-4498
Yoshitomo MorinagaDepartment of Microbiology, Toyama University Graduate School of Medicine and Pharmaceutical Sciences, Toyama, Japan.
Masaharu IsobeCenter for Advanced Antibody Drug Development, University of Toyama, Toyama, Japan.
Nobuyuki KurosawaCenter for Advanced Antibody Drug Development, University of Toyama, Toyama, Japan.ORCID https://orcid.org/0000-0002-1548-4541

Funding

Japan Agency for Medical Research and Development 19187977Japan Agency for Medical Research and Development 20333128Japan Agency for Medical Research and Development 22723616Japan Society for the Promotion of Science 22H02875
6 · The paper itself

Abstract

Intranasal vaccination is an attractive strategy for preventing COVID-19 disease as it stimulates the production of multimeric secretory immunoglobulin A (IgA), the predominant antibody isotype in the mucosal immune system, at the target site of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry. Currently, intranasal vaccine efficacy is evaluated based on the measurement of polyclonal antibody titers in nasal lavage fluid. However, how individual multimeric secretory IgA protects the mucosa from SARS-CoV-2 infection remains to be elucidated. To understand the precise contribution and molecular nature of multimeric secretory IgA induced by intranasal vaccines, we developed 99 monoclonal IgA clones from nasal mucosa and 114 monoclonal IgA or IgG clones from nonmucosal tissues of mice that were intranasally immunized with the SARS-CoV-2 spike protein. The nonmucosal IgA clones exhibited shared origins and common and unique somatic mutations with the related nasal IgA clones, indicating that the antigen-specific plasma cells in the nonmucosal tissues originated from B cells stimulated at the nasal mucosa. Comparing the spike protein binding reactivity, angiotensin-converting enzyme-2-blocking, and in vitro SARS-CoV-2 virus neutralization of monomeric and multimeric secretory IgA pairs recognizing different epitopes showed that even non-neutralizing monomeric IgAs, which represent 70% of the nasal IgA repertoire, can protect against SARS-CoV-2 infection when expressed as multimeric secretory IgAs. We also demonstrated that the intranasal administration of multimeric secretory IgA delivered as prophylaxis in the hamster model reduced infection-induced weight loss. Our investigation is the first to demonstrate the function of nasal IgA at the monoclonal level, showing that nasal immunization can provide effective immunity against SARS-CoV-2 by inducing multimeric secretory IgAs at the target site of the virus infection.

Indexed as

Antibodies, ViralCOVID-19COVID-19 VaccinesImmunoglobulin AImmunoglobulin A, SecretoryNasal MucosaSARS-CoV-2Spike Glycoprotein, CoronavirusAdministration, IntranasalAnimalsAntibodies, MonoclonalAntibodies, NeutralizingFemaleHumansMiceMice, Inbred BALB CAntibodies, MonoclonalAntibodies, NeutralizingAntibodies, ViralCOVID-19 VaccinesImmunoglobulin AImmunoglobulin A, SecretorySpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2COVID-19IgAimmunologyinflammationintranasal vaccinationmonoclonal antibodymouseplasma cellSARS-CoV-2

Identifiers

PMID40338637
PMCPMC12061477

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.