DNA vaccination against a fish rhabdovirus promotes an early chemokine-related recruitment of B cells to the muscle

Rosario Castro, Susana Martínez-Alonso, Uwe Fischer, Neila Álvarez de Haro, Verónica Soto-Lampe, Tiehui Wang, Christopher J Secombes, Niels Lorenzen, Ellen Lorenzen, Carolina Tafalla

Research output: Contribution to journalArticlepeer-review

42 Citations (Scopus)

Abstract

In fish, intramuscular (i.m) injection of plasmid DNA encoding viral proteins has proved a highly effective vaccination strategy against some viral pathogens. The efficacy of DNA vaccination in teleost fish is based on the high level of viral antigen expression in muscle cells inducing a strong and long-lasting protection. However, the mechanisms through which this protection is established and effectuated in fish are still not fully understood. Moreover, similarities to mammalian models cannot be established since DNA vaccination in mammals usually induces much weaker responses. In this work, we have focused on the characterization of the immune cells that infiltrate the muscle at the site of DNA injection in vaccinated fish and the chemokines and chemokine receptors that may be involved in their infiltration. We have demonstrated through diverse techniques that B lymphocytes, both IgM⁺ and IgT⁺ cells, represented a major infiltrating cell type in fish vaccinated with a viral haemorrhagic septicaemia virus (VHSV) glycoprotein-encoding DNA vaccine, whereas in control fish injected with an oil adjuvant mainly granulocyte/monocyte-type cells were attracted. Among twelve chemokine genes studied, only CXCL11_L1, CK5B and CK6 mRNA levels were up-regulated in DNA vaccinated fish compared to fish injected with the corresponding vector backbone. Furthermore, the transcription of CXCR3B, a possible receptor for CXCL11_L1 was also significantly up-regulated in vaccinated fish. Finally, experiments performed with recombinant trout CK5B and CK6 and chemokine expression plasmids revealed that these chemokines have chemotactic capacities which might explain the recruitment of B cells to the site of DNA injection. Altogether, our results reveal that there is an early chemokine-related B cell recruitment triggered by i.m. DNA vaccination against VHSV which might play an important role in the initial phase of the immune response.

Original languageEnglish
Pages (from-to)1160-1168
Number of pages9
JournalVaccine
Volume32
Issue number10
Early online date27 Nov 2013
DOIs
Publication statusPublished - 26 Feb 2014

Bibliographical note

Copyright © 2013 Elsevier Ltd. All rights reserved.
This work was supported by the European Research Council (ERC Starting Grant 2011 280469) and by the European Commission under the 7th Framework Programme for Research and Technological Development (FP7) of the European Union (Grant Agreement 311993 TARGETFISH). Support was also received from the Danish Council for Strategic Research, grant 2101-08-0017 Dafinet. The authors want to thank Oriol Sunyer for providing the anti-IgT antibody used in flow cytometry. Kurt Buchmann and Karsten Skjoedt are also acknowledged for providing the monoclonal antibodies against IgM and IgT used in immunohistochemistry. We also thank Pierre Boudinot for the critical reading of the manuscript.

Keywords

  • animals
  • B-lymphocytes
  • chemokines
  • hemorrhagic septicemia, viral
  • injections, intramuscular
  • muscles
  • novirhabdovirus
  • Oncorhynchus mykiss
  • vaccines, DNA
  • viral vaccines

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