Rabies vaccination induces a CD4+ TEM and CD4+CD8+ TEMRA TH1 phenotype in dogs.

The canine rabies vaccine consists of the whole killed rabies virus and an alum adjuvant. While it is known to provide immunological protection in dogs, its effects on cell-mediated responses remain largely uncharacterized. Here, we analyzed blood and spleen samples from vaccinated dogs to understan...

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Main Authors: Haeree P Lang, Farah F Almeer, Marc K Jenkins, Steven G Friedenberg
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2025-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0323823
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author Haeree P Lang
Farah F Almeer
Marc K Jenkins
Steven G Friedenberg
author_facet Haeree P Lang
Farah F Almeer
Marc K Jenkins
Steven G Friedenberg
author_sort Haeree P Lang
collection DOAJ
description The canine rabies vaccine consists of the whole killed rabies virus and an alum adjuvant. While it is known to provide immunological protection in dogs, its effects on cell-mediated responses remain largely uncharacterized. Here, we analyzed blood and spleen samples from vaccinated dogs to understand adaptive immune responses ex vivo following restimulation with rabies vaccine antigens. Our results showed that recombinant rabies virus glycoprotein (RABV-G) elicited higher antibody titers and IFNγ production compared to recombinant rabies virus nucleoprotein (RABV-N). CD4+ and CD4+CD8+ double-positive (DP) T cells proliferate robustly after five days of RABV-G stimulation, which was inhibited by an anti-canine MHC class II blocking antibody. Both RABV-G-specific CD4+ and DP T cells demonstrated a polarized TH1 phenotype, with minor subsets showing TH1/TH17 hybrid and pathogenic TH1/TH17 hybrid cell features. CD4+ T cells were primarily effector memory T cells (TEM), while DP T cells exhibited a terminally differentiated effector memory phenotype that re-expressed CD45RA (TEMRA). Both RABV-G-specific CD4+ and DP T cells were detectable up to 1,024 days post-vaccination in spleen samples and their proliferative capacities were unaffected by age. Our results provide the first characterization of canine RABV-G-specific T cell phenotypes in the spleen and blood following rabies vaccination.
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publishDate 2025-01-01
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spelling doaj-art-dde312e9dce7477b9c2c5c6d4a75dcc82025-08-20T03:51:20ZengPublic Library of Science (PLoS)PLoS ONE1932-62032025-01-01205e032382310.1371/journal.pone.0323823Rabies vaccination induces a CD4+ TEM and CD4+CD8+ TEMRA TH1 phenotype in dogs.Haeree P LangFarah F AlmeerMarc K JenkinsSteven G FriedenbergThe canine rabies vaccine consists of the whole killed rabies virus and an alum adjuvant. While it is known to provide immunological protection in dogs, its effects on cell-mediated responses remain largely uncharacterized. Here, we analyzed blood and spleen samples from vaccinated dogs to understand adaptive immune responses ex vivo following restimulation with rabies vaccine antigens. Our results showed that recombinant rabies virus glycoprotein (RABV-G) elicited higher antibody titers and IFNγ production compared to recombinant rabies virus nucleoprotein (RABV-N). CD4+ and CD4+CD8+ double-positive (DP) T cells proliferate robustly after five days of RABV-G stimulation, which was inhibited by an anti-canine MHC class II blocking antibody. Both RABV-G-specific CD4+ and DP T cells demonstrated a polarized TH1 phenotype, with minor subsets showing TH1/TH17 hybrid and pathogenic TH1/TH17 hybrid cell features. CD4+ T cells were primarily effector memory T cells (TEM), while DP T cells exhibited a terminally differentiated effector memory phenotype that re-expressed CD45RA (TEMRA). Both RABV-G-specific CD4+ and DP T cells were detectable up to 1,024 days post-vaccination in spleen samples and their proliferative capacities were unaffected by age. Our results provide the first characterization of canine RABV-G-specific T cell phenotypes in the spleen and blood following rabies vaccination.https://doi.org/10.1371/journal.pone.0323823
spellingShingle Haeree P Lang
Farah F Almeer
Marc K Jenkins
Steven G Friedenberg
Rabies vaccination induces a CD4+ TEM and CD4+CD8+ TEMRA TH1 phenotype in dogs.
PLoS ONE
title Rabies vaccination induces a CD4+ TEM and CD4+CD8+ TEMRA TH1 phenotype in dogs.
title_full Rabies vaccination induces a CD4+ TEM and CD4+CD8+ TEMRA TH1 phenotype in dogs.
title_fullStr Rabies vaccination induces a CD4+ TEM and CD4+CD8+ TEMRA TH1 phenotype in dogs.
title_full_unstemmed Rabies vaccination induces a CD4+ TEM and CD4+CD8+ TEMRA TH1 phenotype in dogs.
title_short Rabies vaccination induces a CD4+ TEM and CD4+CD8+ TEMRA TH1 phenotype in dogs.
title_sort rabies vaccination induces a cd4 tem and cd4 cd8 temra th1 phenotype in dogs
url https://doi.org/10.1371/journal.pone.0323823
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