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Rabies vaccination induces a CD4+ TEM and CD4+CD8+ TEMRA TH1 phenotype in dogs
Haeree P Lang1,2, Farah F Almeer2, Marc K Jenkins1
1Center for Immunology, University of Minnesota, Minneapolis, Minnesota, United States of America.
Plos One
|May 12, 2025
Summary
Rabies vaccination in dogs stimulates adaptive immunity, with the rabies virus glycoprotein (RABV-G) driving significant T cell responses. These specific T cells, crucial for long-term immunity, persist for years post-vaccination.
Area of Science:
- Immunology
- Veterinary Medicine
- Vaccinology
Background:
- Canine rabies vaccines provide protection but their impact on cell-mediated immunity is not well understood.
- Understanding adaptive immune responses is key to improving vaccine efficacy.
Purpose of the Study:
- To characterize the cell-mediated immune response in dogs following rabies vaccination.
- To investigate the phenotype and longevity of T cells specific to rabies vaccine antigens.
Main Methods:
- Analysis of blood and spleen samples from vaccinated dogs.
- Ex vivo restimulation with recombinant rabies virus glycoprotein (RABV-G) and nucleoprotein (RABV-N).
- Flow cytometry to identify T cell subsets (CD4+, CD4+CD8+ DP) and their phenotypes (TH1, TEM, TEMRA).
Main Results:
- RABV-G induced higher antibody titers and IFNγ production than RABV-N.
- RABV-G stimulated robust proliferation of CD4+ and CD4+CD8+ double-positive (DP) T cells, dependent on MHC class II.
- RABV-G-specific CD4+ and DP T cells exhibited TH1 and effector memory phenotypes, persisting for over 1000 days post-vaccination.
Conclusions:
- Rabies vaccination elicits robust and long-lasting antigen-specific T cell responses in dogs.
- The study provides the first detailed characterization of canine T cell phenotypes following rabies vaccination.
- RABV-G is a key antigen driving adaptive cell-mediated immunity in canine rabies vaccines.

