Replication-deficient rabies virus-based vaccines are safe and immunogenic in mice and nonhuman primates.
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.
Cenna
Jonathan
J
Department of Microbiology and Immunology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Hunter
Meredith
M
Tan
Gene S
GS
Papaneri
Amy B
AB
Ribka
Erin P
EP
Schnell
Matthias J
MJ
Marx
Preston A
PA
McGettigan
James P
JP
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood*; D000915:Antibody Affinity; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D017353:Gene Deletion; D008253:Macaca mulatta; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D011818:Rabies / Q000276:immunology / Q000517:prevention & control*; D011819:Rabies Vaccines / Q000009:adverse effects / Q000276:immunology*; D011820:Rabies virus / Q000502:physiology*; D014613:Vaccines, Attenuated / Q000009:adverse effects / Q000276:immunology*; D014779:Virus Replication
D000914:Antibodies, Viral; D004268:DNA-Binding Proteins; D011819:Rabies Vaccines; C499308:Rag2 protein, mouse; D014613:Vaccines, Attenuated