Investigating the role for IL-21 in rabies virus vaccine-induced immunity.
Over two-thirds of the world's population lives in regions where rabies is endemic, resulting in over 15 million people receiving multi-dose post-exposure prophylaxis (PEP) and over 55,000 deaths per year globally. A major goal in rabies virus (RABV) research is to develop a single-dose PEP tha...
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ftdoajarticles:oai:doaj.org/article:c660e49a54cc435490a9ad5b0357a074 2023-05-15T15:17:14+02:00 Investigating the role for IL-21 in rabies virus vaccine-induced immunity. Corin L Dorfmeier Evgeni P Tzvetkov Anthony Gatt James P McGettigan 2013-01-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0002129 https://doaj.org/article/c660e49a54cc435490a9ad5b0357a074 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC3597479?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0002129 https://doaj.org/article/c660e49a54cc435490a9ad5b0357a074 PLoS Neglected Tropical Diseases, Vol 7, Iss 3, p e2129 (2013) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2013 ftdoajarticles https://doi.org/10.1371/journal.pntd.0002129 2022-12-31T13:04:06Z Over two-thirds of the world's population lives in regions where rabies is endemic, resulting in over 15 million people receiving multi-dose post-exposure prophylaxis (PEP) and over 55,000 deaths per year globally. A major goal in rabies virus (RABV) research is to develop a single-dose PEP that would simplify vaccination protocols, reduce costs associated with RABV prevention, and save lives. Protection against RABV infections requires virus neutralizing antibodies; however, factors influencing the development of protective RABV-specific B cell responses remain to be elucidated. Here we used a mouse model of IL-21 receptor-deficiency (IL-21R-/-) to characterize the role for IL-21 in RABV vaccine-induced immunity. IL-21R-/- mice immunized with a low dose of a live recombinant RABV-based vaccine (rRABV) produced only low levels of primary or secondary anti-RABV antibody response while wild-type mice developed potent anti-RABV antibodies. Furthermore, IL-21R-/- mice immunized with low-dose rRABV were only minimally protected against pathogenic RABV challenge, while all wild-type mice survived challenge, indicating that IL-21R signaling is required for antibody production in response to low-dose RABV-based vaccination. IL-21R-/- mice immunized with a higher dose of vaccine produced suboptimal anti-RABV primary antibody responses, but showed potent secondary antibodies and protection similar to wild-type mice upon challenge with pathogenic RABV, indicating that IL-21 is dispensable for secondary antibody responses to live RABV-based vaccines when a primary response develops. Furthermore, we show that IL-21 is dispensable for the generation of Tfh cells and memory B cells in the draining lymph nodes of immunized mice but is required for the detection of optimal GC B cells or plasma cells in the lymph node or bone marrow, respectively, in a vaccine dose-dependent manner. Collectively, our preliminary data show that IL-21 is critical for the development of optimal vaccine-induced primary but not secondary antibody ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLoS Neglected Tropical Diseases 7 3 e2129 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
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English |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Corin L Dorfmeier Evgeni P Tzvetkov Anthony Gatt James P McGettigan Investigating the role for IL-21 in rabies virus vaccine-induced immunity. |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Over two-thirds of the world's population lives in regions where rabies is endemic, resulting in over 15 million people receiving multi-dose post-exposure prophylaxis (PEP) and over 55,000 deaths per year globally. A major goal in rabies virus (RABV) research is to develop a single-dose PEP that would simplify vaccination protocols, reduce costs associated with RABV prevention, and save lives. Protection against RABV infections requires virus neutralizing antibodies; however, factors influencing the development of protective RABV-specific B cell responses remain to be elucidated. Here we used a mouse model of IL-21 receptor-deficiency (IL-21R-/-) to characterize the role for IL-21 in RABV vaccine-induced immunity. IL-21R-/- mice immunized with a low dose of a live recombinant RABV-based vaccine (rRABV) produced only low levels of primary or secondary anti-RABV antibody response while wild-type mice developed potent anti-RABV antibodies. Furthermore, IL-21R-/- mice immunized with low-dose rRABV were only minimally protected against pathogenic RABV challenge, while all wild-type mice survived challenge, indicating that IL-21R signaling is required for antibody production in response to low-dose RABV-based vaccination. IL-21R-/- mice immunized with a higher dose of vaccine produced suboptimal anti-RABV primary antibody responses, but showed potent secondary antibodies and protection similar to wild-type mice upon challenge with pathogenic RABV, indicating that IL-21 is dispensable for secondary antibody responses to live RABV-based vaccines when a primary response develops. Furthermore, we show that IL-21 is dispensable for the generation of Tfh cells and memory B cells in the draining lymph nodes of immunized mice but is required for the detection of optimal GC B cells or plasma cells in the lymph node or bone marrow, respectively, in a vaccine dose-dependent manner. Collectively, our preliminary data show that IL-21 is critical for the development of optimal vaccine-induced primary but not secondary antibody ... |
format |
Article in Journal/Newspaper |
author |
Corin L Dorfmeier Evgeni P Tzvetkov Anthony Gatt James P McGettigan |
author_facet |
Corin L Dorfmeier Evgeni P Tzvetkov Anthony Gatt James P McGettigan |
author_sort |
Corin L Dorfmeier |
title |
Investigating the role for IL-21 in rabies virus vaccine-induced immunity. |
title_short |
Investigating the role for IL-21 in rabies virus vaccine-induced immunity. |
title_full |
Investigating the role for IL-21 in rabies virus vaccine-induced immunity. |
title_fullStr |
Investigating the role for IL-21 in rabies virus vaccine-induced immunity. |
title_full_unstemmed |
Investigating the role for IL-21 in rabies virus vaccine-induced immunity. |
title_sort |
investigating the role for il-21 in rabies virus vaccine-induced immunity. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2013 |
url |
https://doi.org/10.1371/journal.pntd.0002129 https://doaj.org/article/c660e49a54cc435490a9ad5b0357a074 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 7, Iss 3, p e2129 (2013) |
op_relation |
http://europepmc.org/articles/PMC3597479?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0002129 https://doaj.org/article/c660e49a54cc435490a9ad5b0357a074 |
op_doi |
https://doi.org/10.1371/journal.pntd.0002129 |
container_title |
PLoS Neglected Tropical Diseases |
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7 |
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3 |
container_start_page |
e2129 |
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