Increase in Virus-Specific Mucosal Antibodies in the Upper Respiratory Tract Following Intramuscular Vaccination of Previously Exposed Horses Against Equine Herpesvirus Type-1/4.
Abstract: Equine herpesvirus type-1 (EHV-1) enters through the upper respiratory tract (URT) and causes respiratory disease, abortions, and myeloencephalopathy in equids. Pre-existing immunity at the viral entry site, especially mucosal IgG4/7 antibodies, has recently been shown to correlate with protection from disease and incomplete viral replication at the URT. Here, we tested whether intramuscular (i.m.) vaccination with a commercial inactivated EHV-1/4 vaccine can induce mucosal antibodies (mucAbs) at the URT. Methods: Adult horses with complete EHV-1 vaccination and/or exposure histories were vaccinated i.m. six times within eight months. Before and after each vaccination, blood and nasal swab samples were obtained. Serum and mucAbs were measured in fluorescent bead-based EHV-1 assays. Results: All horses still had existing EHV-1 specific serum and mucAbs prior to vaccination, which were mainly composed of IgG4/7 antibody isotypes. Serum IgG4/7 significantly increased after the first vaccination and stayed high until the end of the study. An additional short-lasting serum IgG1 response was only induced by the first vaccine application. At the URT, mucAbs increased after five out of six i.m. vaccine injections. Like the systemic antibody response, mucAbs were dominated by IgG4/7 and a small IgG1 increase after the first vaccination. Conclusions: Our data emphasize that robust EHV-1 specific mucAb levels are obtained after i.m. vaccination with the inactivated EHV-1/4 vaccine used here. The findings have important implications for evaluating EHV-1/4 vaccines for their ability to induce and maintain protective mucosal IgG4/7 antibodies.
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Overview
This study investigated whether intramuscular vaccination with an inactivated Equine Herpesvirus type-1/4 (EHV-1/4) vaccine can boost mucosal antibodies in the upper respiratory tract (URT) of horses previously exposed to the virus.
The research found that repeated intramuscular vaccinations increased virus-specific mucosal IgG4/7 antibodies in the URT, which are important for protection against EHV-1 infection.
Background
Equine herpesvirus type-1 (EHV-1) infects horses primarily through the URT, causing respiratory illness, abortions, and neurological symptoms.
Protection against the virus is linked to immunity at the entry site, particularly mucosal antibodies of the IgG4/7 isotype, which can prevent or limit viral replication.
It was unclear whether intramuscular (i.m.) vaccination, which typically induces systemic immunity, could also stimulate mucosal antibody responses in the URT, especially in horses already exposed or vaccinated previously.
Study Methods
Adult horses with known histories of EHV-1 exposure or vaccination were enrolled.
Each horse received six intramuscular doses of a commercial inactivated EHV-1/4 vaccine over an eight-month period.
Samples of blood and nasal swabs were collected before and after each vaccination to measure antibody levels.
Antibody concentrations in serum and mucosal samples were quantified using fluorescent bead-based assays specific to EHV-1.
Key Findings
Before vaccination, horses already had measurable serum and mucosal antibodies against EHV-1, predominantly of the IgG4/7 subtype, likely from prior exposure or vaccination.
After the first vaccination:
The serum IgG4/7 antibody levels increased significantly and remained elevated throughout the study.
An additional, short-lived increase in serum IgG1 antibodies was observed.
In the upper respiratory tract mucosa:
Mucosal antibody levels increased after five of the six vaccine doses.
Similar to serum, mucosal antibodies were mostly IgG4/7, with a small IgG1 rise after the first vaccination.
Implications of the Results
The study demonstrates that intramuscular vaccination can effectively boost mucosal IgG4/7 antibodies in the URT despite prior immunity, which is important because mucosal antibodies at the viral entry site help block infection.
This challenges the common expectation that inactivated vaccines given intramuscularly mainly stimulate systemic immunity but not mucosal responses.
The persistence of mucosal antibody increases after multiple doses suggests that repeated vaccination may be necessary to maintain protective immunity in the URT.
These findings could inform vaccine evaluation and development, highlighting the importance of measuring mucosal IgG4/7 levels as a marker of vaccine-induced protection against EHV-1/4.
Conclusion
Intramuscular administration of an inactivated EHV-1/4 vaccine in horses with prior exposure leads to a robust and sustained increase in virus-specific mucosal IgG4/7 antibodies in the upper respiratory tract.
This mucosal antibody response is critical for protection against EHV-1 infection and provides a relevant endpoint to assess vaccine effectiveness.
The study supports the use of such vaccination protocols to maintain protective mucosal immunity in equine populations at risk of EHV-1/4 infection.
Cite This Article
APA
Wagner B, Schnabel CL, Rollins A.
(2025).
Increase in Virus-Specific Mucosal Antibodies in the Upper Respiratory Tract Following Intramuscular Vaccination of Previously Exposed Horses Against Equine Herpesvirus Type-1/4.
Vaccines (Basel), 13(3), 290.
https://doi.org/10.3390/vaccines13030290
Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
Schnabel, Christiane L
Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
Rollins, Alicia
Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
Grant Funding
NA / This work was supported by the Harry M. Zweig Memorial Fund for Equine Research at Cornell University.
Conflict of Interest Statement
B.W. is the inventor on US patent No. 10/10132 entitled “Enhancing serological assays via fusion proteins”, a technology that is used for the “EHV-1 Risk Evaluation assay” described in this article.
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