Abstract
Viral disease outbreaks remain a significant limiting factor for aquaculture. The majority of licensed vaccines used in the industry are administered as oil-adjuvanted formulations carrying inactivated whole pathogens. Cell-mediated immune responses, in particular those based on virus-specific cytotoxic T-cells (CTLs) to conventional inactivated oil-based vaccines, are largely unexplored. As vaccines cannot be optimized against viral pathogens if knowledge of host cellular immune mechanisms remains unknown, in this study we examined fundamental cell-mediated immune responses after vaccination of rainbow trout with an oil-adjuvanted inactivated vaccine against salmonid alphavirus (SAV) and after infection with SAV. A unique in vitro model system was developed to examine MHC class I restricted CTL responses in a clonal line of rainbow trout. The levels of cell-mediated cytotoxicity were compared to pathology, virus load, specific antibody response, changes in immune cell populations, and mRNA expression. Our results hint that different protective mechanisms are being triggered by infection compared to vaccination. While vaccination itself did not cause a strong cytotoxic or humoral response, subsequent challenge of vaccinated fish resulted in significantly stronger and faster specific cytotoxicity, alongside reduced viral titers and pathology. Hence, testing a vaccine on the capacity to induce cell-mediated cytotoxicity will still require a challenge test. Examination of cellular markers additionally indicates that the initial innate response induced by the vaccine could play an important role in steering adaptive mechanisms.
Highlights
Intensive fish farming is a major global industry
We found a significant increase in the number of CD4+ cells in PBLs only following salmonid alphavirus (SAV) infection, which corresponded to a transitory spike in MHC-II gene expression
Supporting previous work by [74] which found CLEC4T1 and MHC-II expressed on a distinct cell population in rainbow trout following i.p. vaccination, our study found that this putative dendritic marker to be much more highly modulated than the macrophage marker in response to vaccination and infection
Summary
Intensive fish farming is a major global industry. Disease outbreaks remain a significant limiting factor and are considered the single largest cause of economic loss [1,2]. Despite fish having immune mechanisms comparable to higher vertebrates [3,4], farmed fish often fail to mount optimal anti-viral responses and are at high risk from emerging viral diseases [5,6]. Due to limited therapeutic measures, vaccination is the only effective strategy for preventing diseases in aquaculture [7]. The majority of licensed vaccines are administered as oil-adjuvanted formulations carrying inactivated whole pathogens [8]. These inactivated vaccines are successful in inducing immunity against extra-cellular
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