A replication-deficient rabies virus vaccine expressing Ebola virus glycoprotein is highly attenuated for neurovirulence.
We are developing inactivated and live-attenuated rabies virus (RABV) vaccines expressing Ebola virus (EBOV) glycoprotein for use in humans and endangered wildlife, respectively. Here, we further characterize the pathogenesis of the live-attenuated RABV/EBOV vaccine candidates in mice in an effort to define their growth properties and potential for safety. RABV vaccines expressing GP (RV-GP) or a replication-deficient derivative with a deletion of the RABV G gene (RVΔG-GP) are both avirulent after intracerebral inoculation of adult mice. Furthermore, RVΔG-GP is completely avirulent upon intracerebral inoculation of suckling mice unlike parental RABV vaccine or RV-GP. Analysis of RVΔG-GP in the brain by quantitative PCR, determination of virus titer, and immunohistochemistry indicated greatly restricted virus replication. In summary, our findings indicate that RV-GP retains the attenuation phenotype of the live-attenuated RABV vaccine, and RVΔG-GP would appear to be an even safer alternative for use in wildlife or consideration for human use.
Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, MD 21702, USA.
Amy B
AB
Papaneri
Christoph
C
Wirblich
Jennifer A
JA
Cann
Kurt
K
Cooper
Peter B
PB
Jahrling
Matthias J
MJ
Schnell
Joseph E
JE
Blaney
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000473:pathology / Q000821:virology; D004195:Disease Models, Animal; D046129:Ebola Vaccines / Q000009:adverse effects* / Q000235:genetics / Q000276:immunology*; D005260:Female; D017353:Gene Deletion; D005814:Genes, Viral; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D011819:Rabies Vaccines / Q000009:adverse effects* / Q000235:genetics / Q000276:immunology*; D060888:Real-Time Polymerase Chain Reaction; D014613:Vaccines, Attenuated / Q000009:adverse effects / Q000235:genetics / Q000276:immunology; D019562:Viral Load; D014774:Virulence
D046129:Ebola Vaccines; D011819:Rabies Vaccines; D014613:Vaccines, Attenuated