Antibody reactions of horses against various domains of the EHV-1 receptor-binding protein gD1.
Authors: Schramm Andreina, Ackermann Mathias, Eichwald Catherine, Aguilar Claudio, Fraefel Cornel, Lechmann Julia
Journal: PloS one
Summary
# Editorial Summary: Type-Specific Antibody Recognition of EHV-1 Glycoprotein D Distinguishing between EHV-1 and EHV-4 infections remains clinically important given EHV-1's capacity to cause abortion and neurological disease, yet current diagnostic tools rely on glycoprotein G rather than the receptor-binding protein gD—despite the latter's relevance to vaccine design and immunity. Schramm and colleagues developed a panel of luciferase immunoprecipitation assays using progressively larger EHV-1 gD fragments, starting from the N-terminal 83 amino acids through to the full-length 402-amino-acid molecule, and tested these against sera from 60 Swiss horses and 50 Icelandic horses (the latter considered EHV-1 free). Whilst antibodies against the complete gD1 molecule were near-universal across both populations—reflecting high background EHV-4 exposure and cross-reactivity—the N-terminal gD1_83 fragment successfully identified type-specific anti-EHV-1 antibodies, which appeared almost exclusively in vaccinated animals. These findings suggest that current vaccines may inadvertently stimulate responses to epitopes absent from natural EHV-4 infection, and highlight the potential for developing improved diagnostics and vaccines that prioritise type-specific antigens over the cross-reactive domains that dominate natural immunity. For practitioners involved in vaccination protocols and serological testing, this work underscores the need for caution when interpreting gD-based serology and supports the case for next-generation vaccines engineered to avoid type-common epitopes.
Read the full abstract on PubMed
Practical Takeaways
- •Current EHV-1 vaccines may not optimally stimulate protective type-specific immunity due to reliance on cross-reactive antigens shared with EHV-4; future vaccine formulations should prioritize type-specific epitopes like those in the gD1 N-terminus
- •Serological diagnosis of EHV-1 infection remains challenging because anti-gD1 antibodies are predominantly generated by prior EHV-4 exposure; reliance on gG-based discrimination (existing ELISA) is more reliable for EHV-1 versus EHV-4 differentiation
- •Vaccination with current EHV-1 vaccines may not confer robust protection against EHM since type-specific immune responses are poorly developed; practitioners should counsel clients on the limitations of current vaccination protocols in preventing EHM
Key Findings
- •The gD1_83 N-terminal fragment of EHV-1 glycoprotein D identified type-specific antibodies almost exclusively in vaccinated horses, unlike full-length gD1_402 which showed extensive cross-reactivity with EHV-4
- •95% of Swiss sera and 98% of Icelandic sera were seropositive for gD4 (ELISA) and full-length gD1 (LIPS), indicating widespread EHV-4 exposure and substantial cross-reactive antibody responses
- •EHV-1-specific seropositivity (gG1) was rare at 35% in Swiss horses and only 14% in Icelandic horses, demonstrating that most anti-gD1 antibodies result from EHV-4 infection rather than EHV-1