Back to search

FRIMEDBIO-Fri prosj.st. med.,helse,biol

Rational vaccine design as an approach to protect against PMCV infection in salmon

Alternative title: Struktur-basert vaksine mot PMCV infeksjon hos laks

Awarded: NOK 12.0 mill.

Totiviruses are viruses that typically infect protozoa and fungi and some vertebrate species. Salmon is infected with a virus termed piscine myocarditis virus (PMCV) and this virus have acquired the ability to transfer between hosts, an ability lacking in most other totiviruses. PMCV infection is a chronic stage in salmon and causes a severe heart disease termed cardiomyopathy syndrome (CMS) where the wall of the heart becomes so fragile from the damage caused by the virus it can rupture when fish are exposed to physical stress. Fish are infected after sea transfer and the infection progresses over several months up to slaughter size. There are no vaccines available and treatment options do not exist for PMCV infection in salmon. We hypothesize that a better understanding of the virus structure will facilitate vaccine design that can protect against infection and disease. It is likely that antibodies and cell mediated immunity is required to obtain protection. There has to be a match between the virus surface and the antibody that binds the virus and we will identify pathogen-specific antibodies with neutralizing properties, based on detailed scanning of surface domains using sera from survivors of infection and combined with structure studies of the virus particle this will guide us towards optimal vaccine design. We will use recombinant protein design of viral proteins, and test for ability to protect against infection or disease. We will also explore the importance of cell mediated immunity using a vector vaccine approach. Effects from vaccination will be monitored using immunisation and challenge followed by assessment of pathogenic events in the fish. The aim is to develop a vaccine that protect against disease and clinical signs of disease, eventually resulting in reduced mortality and improved welfare.

Totiviridae viruses infect protozoa and fungi while a handful of metazoan totivirus-like viruses infect vertebrates and invertebrates. Salmon piscine myocarditis virus (PMCV) is a totivirus-like viruses, and like dsRNA viruses, metazoan totivirus-like viruses have acquired capsid structures and/or bystander proteins that contribute to extracellular transmission and intra-particle genome transcription. PMCV is the causative agent of cardiomyopathy syndrome (CMS) of Atlantic salmon. PMCV has acquired a unique strategy to adapt to the metazoan host, including two fundamental functions different from the protozoan totiviruses, i.e., extracellular transmission and intra-particle genome transcription. Currently no prophylactic or treatment options exist for PMCV infection in salmon, and our hypothesis is that a better understanding of the PMCV structure will facilitate vaccine design. Further, can protection against infection and/or disease come from antibodies alone or is cell mediated immunity also required. Topological complementarity of the surface contours of the virus particle and the antibody variable domains decides if the antigen is recognized (WP1). Structure-based design relies on which specific sites on the surface protein to target, and we begin with identifying pathogen-specific antibodies with neutralizing properties (WP2). Peptide scanning using sera from survivors of infection will pinpoint domains important for binding, and with structure studies of virus particle and ORF3 protein, this will guide us towards optimal vaccine design. This will be used for recombinant protein design of ORF1 and ORF3 (WP3) encoded viral proteins, and tests for ability to protect against infection/pathology. Next, to explore involvement of cell mediated immunity, a vector vaccine approach is used (WP4) based on attenuated strain of VHS virus expressing ORF1 or ORF3 subdomains. Effects are assessed using immunisation and challenge followed by assessment of pathogenic events.

Funding scheme:

FRIMEDBIO-Fri prosj.st. med.,helse,biol

Funding Sources