There has been the misconception that rabies does not pose a threat to human health anymore due to the highly effective rabies virus vaccine available for prevention and post-exposure treatment. However, it has been overlooked that the current rabies virus vaccine only protects against lyssaviruses of the phylogroup I and not against other, emerging lyssaviruses. Moreover, protection against some members of phylogroup I is less than optimal and requires high antibody titers. This proposal seeks to eventually shift clinical practice paradigms by offering a vaccine with more comprehensive protection against rabies from divergent lyssaviruses. Toward this approach, we will construct novel rabies-virus-based vectors expressing glycoproteins of other lyssaviruses, immunize mice and then characterize the humoral immune response on an antigen microarray of overlapping peptides spanning each of the glycoproteins. The results of these studies will guide us to construct novel G proteins, which should induce a broader immune response against lyssavirus and therefore pave the way toward a novel pan-lyssavirus vaccine.

Public Health Relevance

Rabies is a devastating infectious disease. Anti-rabies virus vaccines and antibodies are not effective against all naturally occurring and emerging rabies-related viruses that can cause the same disease (rabies). Therefore, the development of a vaccine that is broadly efficient against all rabies-related viruses is necessary.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AI128175-02
Application #
9390458
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Park, Eun-Chung
Project Start
2016-12-01
Project End
2019-11-30
Budget Start
2017-12-01
Budget End
2019-11-30
Support Year
2
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Thomas Jefferson University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
053284659
City
Philadelphia
State
PA
Country
United States
Zip Code
19107
Davis, Benjamin M; Fensterl, Volker; Lawrence, Tessa M et al. (2017) Ifit2 Is a Restriction Factor in Rabies Virus Pathogenicity. J Virol 91: