Replication-deficient rabies virus-based vaccines are safe and immunogenic in mice and nonhuman primates

J Infect Dis. 2009 Oct 15;200(8):1251-60. doi: 10.1086/605949.


Although current postexposure prophylaxis rabies virus (RV) vaccines are effective, approximately 40,000-70,000 rabies-related deaths are reported annually worldwide. The development of effective formulations requiring only 1-2 applications would significantly reduce mortality. We assessed in mice and nonhuman primates the efficacy of replication-deficient RV vaccine vectors that lack either the matrix (M) or phosphoprotein (P) gene. A single dose of M gene-deficient RV induced a more rapid and efficient anti-RV response than did P gene-deficient RV immunization. Furthermore, the M gene-deleted RV vaccine induced 4-fold higher virus-neutralizing antibody (VNA) levels in rhesus macaques than did a commercial vaccine within 10 days after inoculation, and at 180 days after immunization rhesus macaques remained healthy and had higher-avidity antibodies, higher VNA titers, and a more potent antibody response typical of a type 1 T helper response than did animals immunized with a commercial vaccine. The data presented in this article suggest that the M gene-deleted RV vaccine is safe and effective and holds the potential of replacing current pre- and postexposure RV vaccines.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Viral / blood*
  • Antibody Affinity
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Female
  • Gene Deletion
  • Macaca mulatta
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Rabies / immunology
  • Rabies / prevention & control*
  • Rabies Vaccines / adverse effects
  • Rabies Vaccines / immunology*
  • Rabies virus / physiology*
  • Vaccines, Attenuated / adverse effects
  • Vaccines, Attenuated / immunology*
  • Virus Replication


  • Antibodies, Viral
  • DNA-Binding Proteins
  • Rabies Vaccines
  • Rag2 protein, mouse
  • Vaccines, Attenuated