Double and quadruple deletion mutant of EHV-1 is highly attenuated and induces optimal immune response.

The research article discusses the development of an enhanced vaccine for Equid alphaherpesvirus 1 (EHV-1). The researchers modified the virus by deleting certain genes, which resulted in a mutant virus that induced a stronger immune response and showed a significant reduction in disease symptoms.

Development of Mutant EHV-1

• The researchers worked on Equid alphaherpesvirus 1 (EHV-1), a virus that causes health issues in equines such as abortion, myeloencephalopathy, and respiratory disease. Although vaccines are available and widely used, EHV-1 outbreaks are still occurring globally. This observation led to the necessity of developing a more effective vaccine.
• The research team utilized gene deletion approach to create attenuated mutant versions of the virus. They deleted virulence and immune evasive associated genes, either individually or combined.

In Vitro Characterization and In Vivo Study

• The generated mutants were examined through in vitro characterization for initial evaluation which followed by an in vivo study using a murine model. This was done to assess the attenuation of the virus and the immune response by the mutants compared to the non-modified (wild type) virus.
• The mutant EHV-1 with the deletion of IR6 and gE genes (identified as vToH-DMV) and those with deletion of four genes (gE, IR6, pUL43, and pUL56 identified as vToH-QMV) showed a notable reduction in plaque size and minimal loss in replication efficacy relative to the wild type virus.

Virus Attenuation and Improved Immune Responses

• In vivo studies demonstrated the virus’s attenuation, evident through a significant decrease in clinical symptoms, weight loss, gross, and histopathological lesions compared to the wild type virus.
• The EHV-1 mutants also stimulated improved immune responses, as observed through serum neutralization and flow cytometric analysis of CD4+ and CD8+ cell populations.
• The findings hence suggest that these EHV-1 mutants (vToH-DMV and vToH-QMV) can serve as potential vaccine candidates, making them worth investigating further to examine their protective efficacy with wild type virus challenge.