Scientific reportsNov 4, 2025

Stronger Mucosal Immunity Against Flu and COVID-19 Using Different mRNA and Protein Vaccines Targeting Key Virus Parts

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jun 27, 2026

Abstract

Essence

An mRNA prime plus PICKCa-adjuvanted intranasal protein boost strengthened mucosal immunity and gave the best influenza challenge protection for a combined influenza-COVID-19 vaccine design.

Evidence

This preclinical vaccine-regimen experiment compared chimeric HA-stem/S-RBD mRNA priming followed by intranasal protein boosts, measuring systemic antibodies, nasal and BALF IgA, and lethal influenza challenge protection.

Caveat

The key protection result was a preclinical high-dose influenza challenge, so human efficacy and direct SARS-CoV-2 challenge protection from this regimen remain unresolved.

Simplified

Influenza virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as two highly contagious respiratory pathogens, continue to pose critical challenges to global public health. In our previous research, we successfully developed mRNA and protein vaccines by integrating the HA stem of H1N1 influenza virus with the RBD from SARS-CoV-2, which demonstrated broad protective efficacy against multiple strains of both viruses in mouse models. Here, we compared the immunogenicity and protective efficacy of heterologous sequential immunization regimens based on this chimeric antigen design, employing mRNA vaccine priming followed by intranasal protein vaccine boosting. Our results show that an mRNA vaccine prime followed by an intranasally administered protein vaccine with boost not only induces robust systemic humoral immunity but also significantly enhances respiratory mucosal immunity. Compared to boosting with an adjuvant-free intranasal protein vaccine, the inclusion of PICKCa adjuvant markedly elevated mucosal IgA levels in both nasal washes and bronchoalveolar lavage fluid (BALF). Furthermore, the adjuvanted intranasal protein vaccine boost regimen provided optimal protection against high-dose lethal influenza virus challenge. These findings provide valuable insights for refining immunization strategies to enhance the efficacy of combined influenza-COVID-19 vaccines.

Key numbers

100%

Survival Rate

Survival rate of vaccinated mice post-influenza challenge.

Higher levels of in nasal washes and

Mucosal Increase

Comparison of levels in different vaccination groups.

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Stronger Mucosal Immunity Against Flu and COVID-19 Using Different mRNA and Protein Vaccines Targeting Key Virus Parts

Abstract

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