Use of Poly(I:C) Stabilized with Chitosan As a Vaccine-Adjuvant Against Viral Hemorrhagic Septicemia Virus Infection in Zebrafish.
There is an urgent need for more efficient viral vaccines in finfish aquaculture worldwide. Here, we report the use of poly(I:C) stabilized with chitosan as an adjuvant for development of better finfish vaccines. The adjuvant was co-injected with inactivated viral hemorrhagic septicemia virus (VHSV) (CSpIC+iV vaccine) in adult zebrafish and its efficiency in protection against VHSV infection was compared to a live, attenuated VHS virus vaccine (aV). Both free and stabilized poly(I:C) were strong inducers of an antiviral state, measured by transcriptional activation of the genes of viral sensors: toll-like receptors, interferons, and interferon-stimulated genes, such as MXa within 48 h after injection. Both the CSpIC+iV and the aV formulations provided a significant protection against VHSV-induced mortality. However, when plasma from survivors was tested for neutralizing antibodies in an in vitro protection assay, we could not demonstrate any protective effect. On the contrary, plasma from aV vaccinated fish enhanced cytopathic effects, indicating that antibody-dependent entry may play a role in this system. Our results show that poly(I:C) is a promising candidate as an adjuvant for fish vaccination against viral pathogens, and that the zebrafish is a promising model for aquaculture-relevant vaccination studies.
1 Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo , Oslo, Norway .
Arturas
A
Kavaliauskis
1 Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo , Oslo, Norway .
Marianne
M
Arnemo
2 Faculty of Veterinary Medicine and Biosciences, Norwegian University of Life Sciences , Oslo, Norway .
Sung-Hyun
SH
Kim
3 Department of Biosciences, University of Oslo , Oslo, Norway .
Lilia
L
Ulanova
3 Department of Biosciences, University of Oslo , Oslo, Norway .
Martin
M
Speth
4 Institute of Marine Research, CSIC , Vigo, Spain .
Beatriz
B
Novoa
4 Institute of Marine Research, CSIC , Vigo, Spain .
Sonia
S
Dios
2 Faculty of Veterinary Medicine and Biosciences, Norwegian University of Life Sciences , Oslo, Norway .
Øystein
Ø
Evensen
3 Department of Biosciences, University of Oslo , Oslo, Norway .
Gareth Wyn
GW
Griffiths
1 Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo , Oslo, Norway .
Tor
T
Gjøen
D000276:Adjuvants, Immunologic; D000818:Animals; D002478:Cells, Cultured; D048271:Chitosan / Q000737:chemistry*; D060226:Head Kidney / Q000166:cytology / Q000378:metabolism; D031941:Hemorrhagic Septicemia, Viral / Q000517:prevention & control* / Q000821:virology; D029141:Novirhabdovirus / Q000276:immunology*; D011070:Poly I-C; D011119:Polynucleotides / Q000737:chemistry / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology*; D015027:Zebrafish
D000276:Adjuvants, Immunologic; D011119:Polynucleotides; D014765:Viral Vaccines; D048271:Chitosan; D011070:Poly I-C