A chimpanzee adenoviral vector-based rabies vaccine protects beagle dogs from lethal rabies virus challenge

Virology. 2019 Oct:536:32-38. doi: 10.1016/j.virol.2019.07.022. Epub 2019 Jul 26.

Abstract

Rabies continues to poses serious threats to the public health in many countries. The development of novel inexpensive, safe and effective vaccines has become a high priority for rabies control worldwide. We previously generated a novel recombinant rabies vaccine by cloning rabies virus glycoprotein into a chimpanzee adenoviral vector, termed ChAd68-Gp. The present study evaluated the immune responses and protection afforded by this vaccine in beagle dogs. The results demonstrated that intramuscular immunization with both low-dose and high-dose of ChAd68-Gp induced strong immune responses and provided complete protection in beagles even at low-dose. However, when administered orally, high-dose vaccination was protective while low-dose vaccination was ineffective. Further investigation indicated that the low-pH value of gastric juice in the stomach of beagles might decompose the adenovirus. Therefore, suitable formulation for adenovirus-based oral vaccine should be considered and developed. The chimpanzee adenovirus-vectored rabies vaccine ChAd68-Gp warrants extensive test for clinical application.

Keywords: Adenoviral vector; Beagle; ChAd68-Gp; Immune responses; Rabies vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviruses, Simian / genetics*
  • Adenoviruses, Simian / immunology
  • Administration, Oral
  • Animals
  • Antibodies, Neutralizing / biosynthesis*
  • Antibodies, Viral / biosynthesis*
  • Dogs
  • Female
  • Genetic Vectors / chemistry
  • Genetic Vectors / immunology
  • Hydrogen-Ion Concentration
  • Immune Sera / administration & dosage
  • Injections, Intramuscular
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Rabies / mortality
  • Rabies / pathology
  • Rabies / prevention & control*
  • Rabies / virology
  • Rabies Vaccines / administration & dosage*
  • Rabies Vaccines / genetics
  • Rabies Vaccines / immunology
  • Rabies virus / drug effects*
  • Rabies virus / genetics
  • Rabies virus / immunology
  • Rabies virus / pathogenicity
  • Survival Analysis
  • Vaccination / methods
  • Vaccines, Synthetic
  • Viral Envelope Proteins / administration & dosage*
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / immunology

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Immune Sera
  • Rabies Vaccines
  • Vaccines, Synthetic
  • Viral Envelope Proteins