title: Replication-deficient rabies virus-based vaccines are safe and immunogenic in mice and nonhuman primates.
abstract: 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.
authors.affiliation: Department of Microbiology and Immunology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Cenna
authors.forename: Meredith
authors.initials: M
authors.lastname: Hunter
authors.forename: Gene S
authors.initials: GS
authors.lastname: Tan
authors.forename: Amy B
authors.initials: AB
authors.lastname: Papaneri
authors.forename: Erin P
authors.initials: EP
authors.lastname: Ribka
authors.forename: Matthias J
authors.initials: MJ
authors.lastname: Schnell
authors.forename: Preston A
authors.initials: PA
authors.lastname: Marx
authors.forename: James P
authors.initials: JP
authors.lastname: McGettigan
mesh_terms: 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
chemical_list: D000914:Antibodies, Viral; D004268:DNA-Binding Proteins; D011819:Rabies Vaccines; C499308:Rag2 protein, mouse; D014613:Vaccines, Attenuated