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, ∼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 p...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of infectious diseases 2009-10, Vol.200 (8), p.1251-1260
Main Authors: Cenna, Jonathan, Hunter, Meredith, Tan, Gene S., Papaneri, Amy B., Ribka, Erin P., Schnell, Matthias J., Marx, Preston A., McGettigan, James P.
Format: Article
Language:English
Subjects:
Animals
Antibodies
Antibodies, Viral - blood
Antibody Affinity
Applied microbiology
Biological and medical sciences
Cell lines
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
Dosage
Female
Fundamental and applied biological sciences. Psychology
Gene Deletion
Immunization
Infections
Infectious diseases
Inoculation
Macaca mulatta
Male
Medical sciences
Mice
Mice, Inbred BALB C
Mice, Knockout
Microbiology
Miscellaneous
Rabies
Rabies - immunology
Rabies - prevention & control
Rabies Vaccines - adverse effects
Rabies Vaccines - immunology
Rabies virus
Rabies virus - physiology
Vaccination
Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects)
Vaccines, Attenuated - adverse effects
Vaccines, Attenuated - immunology
Virology
Virus Replication
Viruses
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Although current postexposure prophylaxis rabies virus (RV) vaccines are effective, ∼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
ISSN:0022-1899
1537-6613
DOI:10.1086/605949