# Toward Effective Vaccines Against Piscine Orthoreovirus: Challenges and Current Strategies

## TL;DR

This paper reviews the challenges in developing vaccines for Piscine orthoreovirus, which causes disease in salmon, and highlights current strategies to improve vaccine effectiveness.

## Contribution

The paper provides a comprehensive review of PRV vaccine development challenges and proposes future strategies for optimized antigen design and delivery.

## Key findings

- PRV cannot be easily propagated in cell lines, hindering vaccine development.
- DNA vaccines encoding σ1 and μNS show partial efficacy due to better antigen presentation.
- Immune variability among fish and viral genotypes complicates vaccine effectiveness.

## Abstract

Piscine orthoreovirus (PRV) is a globally distributed viral pathogen that causes heart and skeletal muscle inflammation (HSMI) in Atlantic salmon (Salmo salar) and affects other salmonids, yet no commercial vaccines are currently available. Major barriers to vaccine development include the inability to propagate PRV in cell lines and the low, variable immunogenicity of its proteins, particularly the outer capsid protein σ1, which mediates viral attachment. This protein is hypothesized to be immunologically relevant due to its homology with Mammalian orthoreoviruses. Recombinant σ1 expressed in conventional systems exhibits poor antibody recognition, whereas structural modifications such as lipidation or fusion with molecular chaperones improve epitope exposure. Formalin-inactivated vaccines have shown inconsistent protection, often failing to elicit robust innate or adaptive responses, especially under cohabitation challenge. In contrast, DNA vaccines encoding σ1 and the non-structural protein μNS have demonstrated partial efficacy, likely due to enhanced intracellular expression and antigen presentation. Nonetheless, the considerable variability observed in immune responses among individual fish and viral genotypes, together with suggestions that PRV may interfere with antiviral pathways, represent additional barriers to achieving consistent vaccine efficacy. This review summarizes the current status of PRV vaccine development and discusses future directions for rational design based on optimized antigens and intracellular delivery platforms.