Newcastle disease virus-vectored rabies vaccine is safe, highly immunogenic, and provides long-lasting protection in dogs and cats

J Virol. 2011 Aug;85(16):8241-52. doi: 10.1128/JVI.00519-11. Epub 2011 Jun 1.

Abstract

Effective, safe, and affordable rabies vaccines are still being sought. Newcastle disease virus (NDV), an avian paramyxovirus, has shown promise as a vaccine vector for mammals. Here, we generated a recombinant avirulent NDV La Sota strain expressing the rabies virus glycoprotein (RVG) and evaluated its potential to serve as a vaccine against rabies. The recombinant virus, rL-RVG, retained its high-growth property in chicken eggs, with titers of up to 10⁹·⁸ 50% egg infective doses (EID₅₀)/ml of allantoic fluid. RVG expression enabled rL-RVG to spread from cell to cell in a rabies virus-like manner, and RVG was incorporated on the surface of the rL-RVG viral particle. RVG incorporation did not alter the trypsin-dependent infectivity of the NDV vector in mammalian cells. rL-RVG and La Sota NDV showed similar levels of sensitivity to a neutralization antibody against NDV and similar levels of resistance to a neutralization antibody against rabies virus. Animal studies demonstrated that rL-RVG is safe in several species, including cats and dogs, when administered as multiple high doses of recombinant vaccine. Intramuscular vaccination with rL-RVG induced a substantial rabies virus neutralization antibody response and provided complete protection from challenge with circulating rabies virus strains. Most importantly, rL-RVG induced strong and long-lasting protective neutralization antibody responses to rabies virus in dogs and cats. A low vaccine dose of 10⁸·³ EID₅₀ completely protected dogs from challenge with a circulating strain of rabies virus for more than a year. This is the first study to demonstrate that immunization with an NDV-vectored vaccine can induce long-lasting, systemic protective immunity against rabies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / biosynthesis*
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / biosynthesis
  • Antibodies, Viral / immunology
  • Blotting, Western
  • Cats
  • Cell Line, Tumor
  • Chlorocebus aethiops
  • Cricetinae
  • Dogs
  • Fluorescent Antibody Technique
  • Gene Expression Regulation, Viral
  • Glycoproteins / biosynthesis
  • Glycoproteins / genetics
  • Glycoproteins / immunology
  • Humans
  • Mice
  • Newcastle disease virus / genetics*
  • Newcastle disease virus / immunology*
  • Newcastle disease virus / physiology
  • Rabies / immunology
  • Rabies / prevention & control*
  • Rabies Vaccines* / administration & dosage
  • Rabies Vaccines* / genetics
  • Rabies Vaccines* / immunology
  • Rabies virus / genetics
  • Rabies virus / immunology*
  • Vaccination
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / immunology
  • Vero Cells
  • Viral Envelope Proteins / biosynthesis
  • Viral Envelope Proteins / genetics*
  • Viral Envelope Proteins / immunology*

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Glycoproteins
  • Rabies Vaccines
  • Vaccines, Synthetic
  • Viral Envelope Proteins