A recombinant canine distemper virus expressing interleukin-7 enhances humoral immunity

J Gen Virol. 2019 Apr;100(4):602-615. doi: 10.1099/jgv.0.001247. Epub 2019 Mar 15.

Abstract

Canine distemper (CD) causes gastrointestinal and respiratory and/or neurological signs and results in high morbidity and mortality, remaining a threat to carnivores around the world. Live-attenuated vaccines have been widely used to reduce the number of CD outbreaks, but efforts are still needed to improve immune efficiency. Interleukin-7 (IL-7) has been reported to boost host immunity by recruiting follicle helper T (TFH) or germinal center (GC) B cells. Here, we constructed a recombinant canine distemper virus (rCDV) by reverse genetics and evaluated the properties of six intergenic sites for insertion of a foreign gene. We found that the P/M intergenic region was the optimal site to insert a foreign gene into the CDV genome. The effect of overexpressing IL-7 on rCDV immunogenicity was then evaluated in a mouse model. We found that mice immunized with rCDV-IL7 could not significantly enhance the maturation of dendritic cells (DCs) but significantly facilitated the generation of TFH cells, GC B cells and plasma cells (PCs), as well as the formation of GCs, consequently enhancing the production of CDV-specific neutralizing antibodies and total IgG. Together, these results suggested that the overexpression of IL-7 by rCDV could enhance humoral responses by activating the TFH-GC B-PC axis, which will help to improve vaccines for CD.

Keywords: canine distemper virus; humoral immunity; interleukin-7; vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / immunology
  • B-Lymphocytes / immunology
  • Chlorocebus aethiops
  • Distemper / immunology*
  • Distemper Virus, Canine / immunology*
  • Dogs
  • Female
  • Germinal Center / immunology
  • Immunity, Humoral / immunology*
  • Interleukin-7 / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred ICR
  • T-Lymphocytes, Helper-Inducer / immunology
  • Vaccination / methods
  • Vaccines, Attenuated / immunology
  • Vero Cells
  • Viral Vaccines / immunology

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Interleukin-7
  • Vaccines, Attenuated
  • Viral Vaccines