Efficacy of an autophagy-targeted DNA vaccine against avian leukosis virus subgroup J

Vaccine. 2017 Feb 1;35(5):808-813. doi: 10.1016/j.vaccine.2016.12.034. Epub 2016 Dec 31.

Abstract

Infection with the avian leukosis virus subgroup J (ALV-J) can lead to neoplastic disease in chickens, inflicting significant economic losses to the poultry industry. Recent reports have identified inhibitory effects of ALV-J on autophagy, a process involving in innate and adaptive immunity. Inspired by this connection between autophagy and immunity, we developed a novel DNA vaccine against ALV-J which includes co-administration of rapamycin to stimulate autophagy. To measure the efficacy of the developed prototype vaccine, five experimental groups of seven-day-old chickens was immunized three times at three-week intervals respectively with vector, pVAX1-gp85, pVAX1-gp85-LC3, pVAX1-gp85+rapamycin and pVAX1-gp85-LC3+rapamycin through electroporation. We then tested their antibody titers, cytokine levels and cellular immune responses. The immunoprotective efficacy of the prototype vaccines against the challenge of the ALV-J GD1109 strain was also examined. The results showed that the combination of pVAX1-gp85-LC3 and rapamycin was able to induce the highest antibody titers, and enhance interleukin(IL)-2, IL-10 and interferon (IFN)-γ expression, and the chickens immunized with the combination of pVAX1-gp85-LC3 and rapamycin showed the highest percentage of CD3+CD8+T lymphocytes. Based on our results, we suggest that stimulating autophagy can improve the efficacy of DNA vaccines and that our DNA vaccine shows the potential of being a candidate vaccine against ALV-J. This study provides a novel strategy for developing vaccines against ALV-J.

Keywords: Autophagy; Avian leucosis virus; DNA vaccine; Rapamycin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity / drug effects
  • Animals
  • Antibodies, Viral / biosynthesis
  • Autophagy / drug effects*
  • Autophagy / genetics
  • Autophagy / immunology
  • Avian Leukosis / genetics
  • Avian Leukosis / immunology
  • Avian Leukosis / prevention & control*
  • Avian Leukosis / virology
  • Avian Leukosis Virus / drug effects
  • Avian Leukosis Virus / immunology
  • Chickens
  • Electroporation
  • Genetic Vectors / chemistry
  • Genetic Vectors / immunology
  • Immunity, Innate / drug effects
  • Interferon-gamma / genetics
  • Interferon-gamma / immunology
  • Interleukin-10 / genetics
  • Interleukin-10 / immunology
  • Interleukin-2 / genetics
  • Interleukin-2 / immunology
  • Poultry Diseases / genetics
  • Poultry Diseases / immunology
  • Poultry Diseases / prevention & control*
  • Poultry Diseases / virology
  • Sirolimus / pharmacology*
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • T-Lymphocytes / virology
  • Vaccination*
  • Vaccines, DNA / administration & dosage*
  • Vaccines, DNA / genetics
  • Vaccines, DNA / immunology
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / immunology
  • Viral Vaccines / administration & dosage*
  • Viral Vaccines / genetics
  • Viral Vaccines / immunology

Substances

  • Antibodies, Viral
  • Interleukin-2
  • Vaccines, DNA
  • Viral Envelope Proteins
  • Viral Vaccines
  • Interleukin-10
  • Interferon-gamma
  • Sirolimus