VaccineMay 16, 2026

A modified pig coronavirus spike protein mRNA vaccine shows stronger immune response and better protection than a traditional inactivated vaccine

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗

Updated May 19, 2026

Abstract

The S-2P LNP-mRNA vaccine achieved 100% survival in piglets challenged with virulent PEDV G2c.

Porcine epidemic diarrhea virus (PEDV) causes near 100% mortality in neonatal piglets.
Two mRNA vaccine candidates were developed, one with the wild-type spike protein and another with proline-stabilized mutations.
The S-2P vaccine induced stronger immune responses, including higher levels of IgG and IgA antibodies and neutralizing antibodies, compared to the S-WT vaccine.
Maternal immunization with the S-2P vaccine transferred protective antibodies to piglets through colostrum.
While the vaccines did not significantly protect gut microbiota diversity or intestinal barrier integrity, maternally derived antibodies reduced disease severity.

Simplified

Porcine epidemic diarrhea virus (PEDV) is a highly contagious pathogen causing near 100% mortality in neonatal piglets, posing a persistent threat to the global swine industry. In this study, we isolated a PEDV strain, 23GXNN-1 (genotype G2c), from an outbreak in Guangxi, China. Two mRNA vaccine candidates were developed: one encoding the wild-type spike (S) protein S-WT and another incorporating proline-stabilized mutations (S-2P, I1076P/L1077P). Evaluations in HEK293T cells and animal models (BALB/c mice, sows, and piglets) revealed that the S-2P LNP-mRNA vaccine induced superior immunogenicity compared to S-WT, generating robust humoral immunity (elevated IgG/IgA titers and neutralizing antibodies) and enhanced cellular immune responses. Notably, maternal immunization with S-2P conferred 100% survival in piglets challenged with virulent PEDV G2c via efficient passive transfer of antibodies through colostrum, outperforming commercial inactivated vaccines. While vaccines provide limited protection to gut microbiota diversity and intestinal barrier integrity during infection, maternally derived antibodies effectively reduce disease severity. This study not only identifies S-2P as a promising candidate for PEDV control, but also underscores the crucial role of maternal immunity in neonatal protection, advancing mRNA-based strategies against enteric coronaviruses.

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Competing interests

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Kang Ouyang reports financial support was provided by The Guangxi Key Technologies R&D Program. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

PubMed

A modified pig coronavirus spike protein mRNA vaccine shows stronger immune response and better protection than a traditional inactivated vaccine

Abstract

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Funding

Competing interests

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