Next-generation salmonid alphavirus vaccine development

• Main Author: Hikke, M.C.
• Other Authors: Vlak, Just, Pijlman, Gorben
• Format: Doctoral or Postdoctoral Thesis
• Language: English
• Published: Wageningen University 2016
• Subjects: alphavirus; aquaculture; atlantic salmon; biotechnology; fish culture; immunity; rainbow trout; vaccine development; virology; alfavirus; aquacultuur; biotechnologie; europese zalm; immuniteit; regenboogforel; vaccinontwikkeling; virologie; visteelt; Sav’; Atlantic salmon
• Online Access: https://research.wur.nl/en/publications/next-generation-salmonid-alphavirus-vaccine-development; https://doi.org/10.18174/371265

ABSTRACT Aquaculture is essential to meet the current and future demands for seafood to feed the world population. Atlantic salmon and rainbow trout are two of the most cultured aquaculture species. A pathogen that threatens these species is salmonid alphavirus (SAV). A current inactivated virus vaccine against SAV provides cross-protection against all SAV subtypes in salmonids and reduces mortality amongst infected fish. However, protection is not 100% and due to virus growth at low temperature, the vaccine production process is time consuming. In addition, the vaccine needs to be injected into the fish, which is a cumbersome process. The work described in this thesis aimed to increase the general knowledge of SAV and to assess current vaccine technologies, and to use this knowledge in designing next-generation vaccines for salmonid aquaculture. An alternative cell line to support SAV proliferation was identified, however, the virus production time could not yet outcompete the current SAV production system. Making use of the baculovirus insect cell expression system, multiple enveloped virus-like particle (eVLP), and core-like particle (CLP) prototype vaccines were produced in insect cells at high temperature. An in vivo vaccination study showed, however, that these vaccines could not readily protect Atlantic salmon against SAV. The low temperature-dependent replication of SAV was attributed to the glycoprotein E2, and it was found that E2 only correctly travelled to the cell surface at low temperature, and in the presence of glycoprotein E1. The biological impact of this finding was confirmed in the development and in vivo testing of a DNA-launched replicon vaccine. The effective DNA-launched replicon vaccine was extended by delivery of the capsid protein in trans. It was hypothesized that viral replicon particles (VRP) were formed in vivo, which would cause an additional single round of infection and might further elevate the immune response in comparison to the replicon vaccine. A second animal trial ...