Cargando…

Cellular Basis for the Enhanced Efficacy of the Fms-Like Tyrosine Kinase 3 Ligand (FL) Adjuvanted VCG-Based Chlamydia abortus Vaccine

Efficacious vaccines are needed to control genital chlamydial diseases in humans and the veterinary industry. We previously reported a C. abortus (Cab) vaccine comprising recombinant Vibrio cholerae ghosts (rVCG) expressing the conserved and immunogenic N-terminal region of the Cab polymorphic membr...

Descripción completa

Detalles Bibliográficos
Autores principales: Richardson, Shakyra, Medhavi, Fnu, Tanner, Tayhlor, Lundy, Stephanie, Omosun, Yusuf, Igietseme, Joseph U., Carroll, Darin, Eko, Francis O.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264281/
https://www.ncbi.nlm.nih.gov/pubmed/34249004
http://dx.doi.org/10.3389/fimmu.2021.698737
_version_ 1783719519350423552
author Richardson, Shakyra
Medhavi, Fnu
Tanner, Tayhlor
Lundy, Stephanie
Omosun, Yusuf
Igietseme, Joseph U.
Carroll, Darin
Eko, Francis O.
author_facet Richardson, Shakyra
Medhavi, Fnu
Tanner, Tayhlor
Lundy, Stephanie
Omosun, Yusuf
Igietseme, Joseph U.
Carroll, Darin
Eko, Francis O.
author_sort Richardson, Shakyra
collection PubMed
description Efficacious vaccines are needed to control genital chlamydial diseases in humans and the veterinary industry. We previously reported a C. abortus (Cab) vaccine comprising recombinant Vibrio cholerae ghosts (rVCG) expressing the conserved and immunogenic N-terminal region of the Cab polymorphic membrane protein D (rVCG-Pmp18.1) protein that protected mice against intravaginal challenge. In this study, we investigated the immunomodulatory effect of the hematopoietic progenitor activator cytokine, Fms-like tyrosine kinase 3-ligand (FL) when co-administered with the rVCG-Pmp18.1 vaccine as a strategy to enhance the protective efficacy and the potential mechanism of immunomodulation. Groups of female C57BL/6J mice were immunized and boosted twice intranasally (IN) with rVCG-PmpD18.1 with and without FL or purified rPmp18.1 or rVCG-gD2 (antigen control) or PBS (medium) per mouse. The results revealed that co-administration of the vaccine with FL enhanced antigen-specific cellular and humoral immune responses and protected against live Cab genital infection. Comparative analysis of immune cell phenotypes infiltrating mucosal and systemic immune inductive tissue sites following immunization revealed that co-administration of rVCG-Pmp18.1 with FL significantly enhanced the number of macrophages, dendritic and NK cells, γδ and NK T cells in the spleen (systemic) and iliac lymph nodes (ILN) draining the genital tract (mucosal) tissues compared to rVCG-Pmp18.1 alone. Furthermore, FL enhanced monocyte infiltration in the ILN, while CD19+ B cells and CD4+ T cells were enhanced in the spleen. These results indicate that the immunomodulatory effect of FL is associated with its ability to mobilize innate immune cells and subsequent activation of robust antigen-specific immune effectors in mucosal and systemic lymphoid tissues.
format Online
Article
Text
id pubmed-8264281
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-82642812021-07-09 Cellular Basis for the Enhanced Efficacy of the Fms-Like Tyrosine Kinase 3 Ligand (FL) Adjuvanted VCG-Based Chlamydia abortus Vaccine Richardson, Shakyra Medhavi, Fnu Tanner, Tayhlor Lundy, Stephanie Omosun, Yusuf Igietseme, Joseph U. Carroll, Darin Eko, Francis O. Front Immunol Immunology Efficacious vaccines are needed to control genital chlamydial diseases in humans and the veterinary industry. We previously reported a C. abortus (Cab) vaccine comprising recombinant Vibrio cholerae ghosts (rVCG) expressing the conserved and immunogenic N-terminal region of the Cab polymorphic membrane protein D (rVCG-Pmp18.1) protein that protected mice against intravaginal challenge. In this study, we investigated the immunomodulatory effect of the hematopoietic progenitor activator cytokine, Fms-like tyrosine kinase 3-ligand (FL) when co-administered with the rVCG-Pmp18.1 vaccine as a strategy to enhance the protective efficacy and the potential mechanism of immunomodulation. Groups of female C57BL/6J mice were immunized and boosted twice intranasally (IN) with rVCG-PmpD18.1 with and without FL or purified rPmp18.1 or rVCG-gD2 (antigen control) or PBS (medium) per mouse. The results revealed that co-administration of the vaccine with FL enhanced antigen-specific cellular and humoral immune responses and protected against live Cab genital infection. Comparative analysis of immune cell phenotypes infiltrating mucosal and systemic immune inductive tissue sites following immunization revealed that co-administration of rVCG-Pmp18.1 with FL significantly enhanced the number of macrophages, dendritic and NK cells, γδ and NK T cells in the spleen (systemic) and iliac lymph nodes (ILN) draining the genital tract (mucosal) tissues compared to rVCG-Pmp18.1 alone. Furthermore, FL enhanced monocyte infiltration in the ILN, while CD19+ B cells and CD4+ T cells were enhanced in the spleen. These results indicate that the immunomodulatory effect of FL is associated with its ability to mobilize innate immune cells and subsequent activation of robust antigen-specific immune effectors in mucosal and systemic lymphoid tissues. Frontiers Media S.A. 2021-06-24 /pmc/articles/PMC8264281/ /pubmed/34249004 http://dx.doi.org/10.3389/fimmu.2021.698737 Text en Copyright © 2021 Richardson, Medhavi, Tanner, Lundy, Omosun, Igietseme, Carroll and Eko https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Richardson, Shakyra
Medhavi, Fnu
Tanner, Tayhlor
Lundy, Stephanie
Omosun, Yusuf
Igietseme, Joseph U.
Carroll, Darin
Eko, Francis O.
Cellular Basis for the Enhanced Efficacy of the Fms-Like Tyrosine Kinase 3 Ligand (FL) Adjuvanted VCG-Based Chlamydia abortus Vaccine
title Cellular Basis for the Enhanced Efficacy of the Fms-Like Tyrosine Kinase 3 Ligand (FL) Adjuvanted VCG-Based Chlamydia abortus Vaccine
title_full Cellular Basis for the Enhanced Efficacy of the Fms-Like Tyrosine Kinase 3 Ligand (FL) Adjuvanted VCG-Based Chlamydia abortus Vaccine
title_fullStr Cellular Basis for the Enhanced Efficacy of the Fms-Like Tyrosine Kinase 3 Ligand (FL) Adjuvanted VCG-Based Chlamydia abortus Vaccine
title_full_unstemmed Cellular Basis for the Enhanced Efficacy of the Fms-Like Tyrosine Kinase 3 Ligand (FL) Adjuvanted VCG-Based Chlamydia abortus Vaccine
title_short Cellular Basis for the Enhanced Efficacy of the Fms-Like Tyrosine Kinase 3 Ligand (FL) Adjuvanted VCG-Based Chlamydia abortus Vaccine
title_sort cellular basis for the enhanced efficacy of the fms-like tyrosine kinase 3 ligand (fl) adjuvanted vcg-based chlamydia abortus vaccine
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264281/
https://www.ncbi.nlm.nih.gov/pubmed/34249004
http://dx.doi.org/10.3389/fimmu.2021.698737
work_keys_str_mv AT richardsonshakyra cellularbasisfortheenhancedefficacyofthefmsliketyrosinekinase3ligandfladjuvantedvcgbasedchlamydiaabortusvaccine
AT medhavifnu cellularbasisfortheenhancedefficacyofthefmsliketyrosinekinase3ligandfladjuvantedvcgbasedchlamydiaabortusvaccine
AT tannertayhlor cellularbasisfortheenhancedefficacyofthefmsliketyrosinekinase3ligandfladjuvantedvcgbasedchlamydiaabortusvaccine
AT lundystephanie cellularbasisfortheenhancedefficacyofthefmsliketyrosinekinase3ligandfladjuvantedvcgbasedchlamydiaabortusvaccine
AT omosunyusuf cellularbasisfortheenhancedefficacyofthefmsliketyrosinekinase3ligandfladjuvantedvcgbasedchlamydiaabortusvaccine
AT igietsemejosephu cellularbasisfortheenhancedefficacyofthefmsliketyrosinekinase3ligandfladjuvantedvcgbasedchlamydiaabortusvaccine
AT carrolldarin cellularbasisfortheenhancedefficacyofthefmsliketyrosinekinase3ligandfladjuvantedvcgbasedchlamydiaabortusvaccine
AT ekofranciso cellularbasisfortheenhancedefficacyofthefmsliketyrosinekinase3ligandfladjuvantedvcgbasedchlamydiaabortusvaccine