Ns1 is a key protein in the vaccine composition to protect Ifnar(-/-) mice against infection with multiple serotypes of African horse sickness virus.
Authors: de la Poza Francisco, Calvo-Pinilla Eva, López-Gil Elena, Marín-López Alejandro, Mateos Francisco, Castillo-Olivares Javier, Lorenzo Gema, Ortego Javier
Journal: PloS one
Summary
# Editorial Summary: NS1 Protein's Role in Multi-Serotype African Horse Sickness Vaccination African horse sickness virus (AHSV) poses a significant threat to equine populations worldwide, with nine recognised serotypes complicating vaccine development; this research examined whether including the non-structural protein NS1 alongside the structural protein VP2 could broaden protective immunity across multiple serotypes. Using immunocompromised mice models, researchers tested two vaccination strategies—a DNA prime followed by modified vaccinia virus Ankara (rMVA) boost, and a homologous rMVA/rMVA approach—both expressing VP2 and NS1 from AHSV-4, measuring neutralising antibody responses, T cell activation, and viral load following challenge with homologous and heterologous serotypes. The rMVA/rMVA strategy proved superior, completely preventing viraemia in animals challenged with AHSV-4 whilst reducing viral load substantially against the heterologous AHSV-9; both vaccination approaches generated cross-protective immunity, with animals showing minimal clinical signs despite heterologous challenge. These findings suggest that incorporating NS1 into vaccine formulations could yield broadly protective multiserotype vaccines—a critical advancement given that current veterinary practice relies on serotype-specific vaccination and movement restrictions during outbreaks. Further investigation in equine models will be essential to translate these promising preclinical results into clinically applicable vaccines that protect against multiple AHSV serotypes simultaneously.
Read the full abstract on PubMed
Practical Takeaways
- •NS1 protein is an essential component of effective AHSV vaccines, not just VP2 alone, for broad serotype coverage
- •rMVA/rMVA homologous boosting strategy shows superior protection compared to heterologous DNA/rMVA approach for preventing viraemia in challenge infections
- •Multi-serotype vaccine formulations including NS1 may protect horses against multiple AHSV strains, reducing need for serotype-specific vaccines
Key Findings
- •DNA/rMVA-VP2-NS1 vaccination generated significant neutralizing antibodies against AHSV-4 with partial homologous protection and cross-protection against AHSV-9
- •rMVA/rMVA homologous prime-boost strategy achieved complete protection against AHSV-4 challenge with no detectable viraemia in vaccinated animals
- •NS1 protein inclusion in vaccine formulations is critical for generating multiserotype protection against multiple AHSV serotypes
- •Both DNA/rMVA and rMVA/rMVA strategies provided cross-protective immunity against heterologous AHSV-9 challenge