What question did this study set out to answer?

To examine the emergence and characteristics of the highly virulent G2c subtype of PEDV and its effects on vaccine efficacy.

February 19, 2026Open Access

Emergence of a Highly Virulent Porcine Epidemic Diarrhea Virus (PEDV) G2c Subtype in China: Isolation, Genetic and Pathogenic Characterization, and Cross‐Neutralizing Antibody Response

Key Result

G2c PEDV variants caused 100% mortality in piglets and feedback exposure induced 12-189.3-fold higher neutralizing antibodies than conventional vaccines.

Key Points

To examine the emergence and characteristics of the highly virulent G2c subtype of PEDV and its effects on vaccine efficacy.
Isolated a G2c strain (AHCZ02) from various provinces in China between 2021-2024.
Conducted phylogenetic analysis to identify G2c variants as predominant in outbreaks.
Performed structural modeling to assess S protein modifications.
Tested serum neutralizing antibody responses to compare vaccine effectiveness.
Identified G2c variants in 69.57% of recent outbreaks.
G2c subtype showed significantly higher neutralizing activity compared to conventional vaccines (GMT = 480–1893 vs 10–40).
Achieved 100% mortality in neonatal piglets within 66 hours post-inoculation with AHCZ02, with severe clinical signs observed.

Structured PICO

Population

Neonatal piglets and 69 PEDV S gene sequences from nine provinces in China

Intervention

G2c-based feedback exposure strategies and AHCZ02 strain inoculation

Comparator

S-INDEL-based approaches and conventional vaccines

Outcome

Neutralizing antibody titers and pathogenicity (mortality, clinical manifestations)surrogate

The emergence of highly virulent PEDV G2c variants with S protein modifications compromises conventional vaccine efficacy, highlighting the need for updated vaccines.

Main Result

Absolute Event Rate: 0% vs 0%

Abstract

Porcine epidemic diarrhea virus (PEDV), an enteropathogenic coronavirus causing high mortality in neonatal piglets, continues to threaten global swine industries. Frequent mutations in the spike (S) protein of PEDV, particularly in emerging variants, have substantially compromised commercial vaccine efficacy. Despite the emergence of G2c variants dominating recent epidemics, comprehensive studies integrating viral isolation, phylogenetics, structural modeling, cross‐neutralizing antibody response, and pathogenicity assessment remain insufficient. In this study, we successfully isolated a G2c strain (AHCZ02) and obtained 69 S gene sequences from nine provinces during 2021–2024. Phylogenetic analysis identified G2c variants as predominant (69.57%, 48/69) in current outbreaks. Structural comparisons revealed four G2c‐specific substitutions (N139D, I287M, F345L, and L998M) inducing conformational changes in critical S domains compared to G2a/G2b strains, potentially disrupting immune recognition. The results of serum neutralizing antibody (nAb) test using the AHCZ02 strain showed that G2c‐based feedback exposure strategies elicited 3.9‐fold higher geometric mean titers (GMTs) than S‐INDEL–based approaches. Furthermore, feedback exposure strategies of G2c (GMT = 480–1893) showed 12‐ to 189.3‐fold higher neutralizing activity versus conventional vaccines (GMT = 10–40). Pathogenicity assessment in neonatal piglets revealed 100% mortality within 66 h post‐AHCZ02 inoculation, accompanied by hallmark clinical manifestations including profuse watery diarrhea, rapid weight loss, and severe jejunal villus atrophy. Collectively, these findings provide evidence that G2c variants have developed S protein modifications associated with diminished vaccine efficacy, underscoring the need for next‐generation vaccines incorporating G2c‐specific antigenic determinants, and strengthened virological surveillance systems to effectively monitor and respond to PEDV evolutionary dynamics.