mRNA vaccine-induced IgG mediates nasal SARS-CoV-2 clearance in mice.

Publication date: Dec 10, 2024

Coronavirus disease 2019 (COVID-19) mRNA vaccines that have contributed to controlling the SARS-CoV-2 pandemic induce specific serum antibodies, which correlate with protection. However, the neutralizing capacity of antibodies for emerging SARS-CoV-2 variants is altered. Suboptimal antibody responses are observed in patients with humoral immunodeficiency diseases, ongoing B cell depletion therapy, and aging. Common experimental mouse models with altered B cell compartments, such as B cell depletion or deficiency, do not fully recapitulate scenarios of declining or suboptimal antibody levels as observed in humans. We report on SARS-CoV-2 immunity in a transgenic mouse model with restricted virus-specific antibodies. Vaccination of C57BL/6-Tg(IghelMD4)4Ccg/J mice with unmodified or N1mΨ-modified mRNA encoding for ancestral spike (S) protein and subsequent challenge with mouse-adapted SARS-CoV-2 provided insights into antibody-independent immunity and the impact of antibody titers on mucosal immunity. Protection against fatal disease was independent of seroconversion following mRNA vaccination, suggesting that virus-specific T cells can compensate for suboptimal antibody levels. In contrast, mRNA-induced IgG in the nasal conchae limited the local viral load and disease progression. Our results indicate that parenteral mRNA immunization can elicit nasal IgG antibodies that effectively suppress local viral replication, highlighting the potential of vaccines in controlling SARS-CoV-2 transmission and epidemiology.

Concepts Keywords
Coronavirus antibodies
Mice antibody-deficient mouse
Mrna IgG
Tgighelmd44ccg SARS-CoV-2 MA20
Therapy transmission
upper respiratory tract
viral shedding

Semantics

Type Source Name
disease MESH Coronavirus disease 2019
disease IDO immunodeficiency
disease IDO cell
drug DRUGBANK Tioguanine
disease IDO protein
disease MESH seroconversion
disease MESH viral load
disease MESH disease progression
pathway KEGG Viral replication
disease MESH viral shedding

Original Article

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