Cargando…

4-1BBL Enhances CD8(+) T Cell Responses Induced by Vectored Vaccines in Mice but Fails to Improve Immunogenicity in Rhesus Macaques

T cells play a central role in the immune response to many of the world’s major infectious diseases. In this study we investigated the tumour necrosis factor receptor superfamily costimulatory molecule, 4-1BBL (CD137L, TNFSF9), for its ability to increase T cell immunogenicity induced by a variety o...

Descripción completa

Detalles Bibliográficos
Autores principales: Spencer, Alexandra J., Furze, Julie, Honeycutt, Jared D., Calvert, Alice, Saurya, Saroj, Colloca, Stefano, Wyllie, David H., Gilbert, Sarah C., Bregu, Migena, Cottingham, Matthew G., Hill, Adrian V. S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4139357/
https://www.ncbi.nlm.nih.gov/pubmed/25140889
http://dx.doi.org/10.1371/journal.pone.0105520
_version_ 1782331353976537088
author Spencer, Alexandra J.
Furze, Julie
Honeycutt, Jared D.
Calvert, Alice
Saurya, Saroj
Colloca, Stefano
Wyllie, David H.
Gilbert, Sarah C.
Bregu, Migena
Cottingham, Matthew G.
Hill, Adrian V. S.
author_facet Spencer, Alexandra J.
Furze, Julie
Honeycutt, Jared D.
Calvert, Alice
Saurya, Saroj
Colloca, Stefano
Wyllie, David H.
Gilbert, Sarah C.
Bregu, Migena
Cottingham, Matthew G.
Hill, Adrian V. S.
author_sort Spencer, Alexandra J.
collection PubMed
description T cells play a central role in the immune response to many of the world’s major infectious diseases. In this study we investigated the tumour necrosis factor receptor superfamily costimulatory molecule, 4-1BBL (CD137L, TNFSF9), for its ability to increase T cell immunogenicity induced by a variety of recombinant vectored vaccines. To efficiently test this hypothesis, we assessed a number of promoters and developed a stable bi-cistronic vector expressing both the antigen and adjuvant. Co-expression of 4-1BBL, together with our model antigen TIP, was shown to increase the frequency of murine antigen-specific IFN-γ secreting CD8(+) T cells in three vector platforms examined. Enhancement of the response was not limited by co-expression with the antigen, as an increase in CD8(+) immunogenicity was also observed by co-administration of two vectors each expressing only the antigen or adjuvant. However, when this regimen was tested in non-human primates using a clinical malaria vaccine candidate, no adjuvant effect of 4-1BBL was observed limiting its potential use as a single adjuvant for translation into a clinical vaccine.
format Online
Article
Text
id pubmed-4139357
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-41393572014-08-25 4-1BBL Enhances CD8(+) T Cell Responses Induced by Vectored Vaccines in Mice but Fails to Improve Immunogenicity in Rhesus Macaques Spencer, Alexandra J. Furze, Julie Honeycutt, Jared D. Calvert, Alice Saurya, Saroj Colloca, Stefano Wyllie, David H. Gilbert, Sarah C. Bregu, Migena Cottingham, Matthew G. Hill, Adrian V. S. PLoS One Research Article T cells play a central role in the immune response to many of the world’s major infectious diseases. In this study we investigated the tumour necrosis factor receptor superfamily costimulatory molecule, 4-1BBL (CD137L, TNFSF9), for its ability to increase T cell immunogenicity induced by a variety of recombinant vectored vaccines. To efficiently test this hypothesis, we assessed a number of promoters and developed a stable bi-cistronic vector expressing both the antigen and adjuvant. Co-expression of 4-1BBL, together with our model antigen TIP, was shown to increase the frequency of murine antigen-specific IFN-γ secreting CD8(+) T cells in three vector platforms examined. Enhancement of the response was not limited by co-expression with the antigen, as an increase in CD8(+) immunogenicity was also observed by co-administration of two vectors each expressing only the antigen or adjuvant. However, when this regimen was tested in non-human primates using a clinical malaria vaccine candidate, no adjuvant effect of 4-1BBL was observed limiting its potential use as a single adjuvant for translation into a clinical vaccine. Public Library of Science 2014-08-20 /pmc/articles/PMC4139357/ /pubmed/25140889 http://dx.doi.org/10.1371/journal.pone.0105520 Text en © 2014 Spencer et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Spencer, Alexandra J.
Furze, Julie
Honeycutt, Jared D.
Calvert, Alice
Saurya, Saroj
Colloca, Stefano
Wyllie, David H.
Gilbert, Sarah C.
Bregu, Migena
Cottingham, Matthew G.
Hill, Adrian V. S.
4-1BBL Enhances CD8(+) T Cell Responses Induced by Vectored Vaccines in Mice but Fails to Improve Immunogenicity in Rhesus Macaques
title 4-1BBL Enhances CD8(+) T Cell Responses Induced by Vectored Vaccines in Mice but Fails to Improve Immunogenicity in Rhesus Macaques
title_full 4-1BBL Enhances CD8(+) T Cell Responses Induced by Vectored Vaccines in Mice but Fails to Improve Immunogenicity in Rhesus Macaques
title_fullStr 4-1BBL Enhances CD8(+) T Cell Responses Induced by Vectored Vaccines in Mice but Fails to Improve Immunogenicity in Rhesus Macaques
title_full_unstemmed 4-1BBL Enhances CD8(+) T Cell Responses Induced by Vectored Vaccines in Mice but Fails to Improve Immunogenicity in Rhesus Macaques
title_short 4-1BBL Enhances CD8(+) T Cell Responses Induced by Vectored Vaccines in Mice but Fails to Improve Immunogenicity in Rhesus Macaques
title_sort 4-1bbl enhances cd8(+) t cell responses induced by vectored vaccines in mice but fails to improve immunogenicity in rhesus macaques
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4139357/
https://www.ncbi.nlm.nih.gov/pubmed/25140889
http://dx.doi.org/10.1371/journal.pone.0105520
work_keys_str_mv AT spenceralexandraj 41bblenhancescd8tcellresponsesinducedbyvectoredvaccinesinmicebutfailstoimproveimmunogenicityinrhesusmacaques
AT furzejulie 41bblenhancescd8tcellresponsesinducedbyvectoredvaccinesinmicebutfailstoimproveimmunogenicityinrhesusmacaques
AT honeycuttjaredd 41bblenhancescd8tcellresponsesinducedbyvectoredvaccinesinmicebutfailstoimproveimmunogenicityinrhesusmacaques
AT calvertalice 41bblenhancescd8tcellresponsesinducedbyvectoredvaccinesinmicebutfailstoimproveimmunogenicityinrhesusmacaques
AT sauryasaroj 41bblenhancescd8tcellresponsesinducedbyvectoredvaccinesinmicebutfailstoimproveimmunogenicityinrhesusmacaques
AT collocastefano 41bblenhancescd8tcellresponsesinducedbyvectoredvaccinesinmicebutfailstoimproveimmunogenicityinrhesusmacaques
AT wylliedavidh 41bblenhancescd8tcellresponsesinducedbyvectoredvaccinesinmicebutfailstoimproveimmunogenicityinrhesusmacaques
AT gilbertsarahc 41bblenhancescd8tcellresponsesinducedbyvectoredvaccinesinmicebutfailstoimproveimmunogenicityinrhesusmacaques
AT bregumigena 41bblenhancescd8tcellresponsesinducedbyvectoredvaccinesinmicebutfailstoimproveimmunogenicityinrhesusmacaques
AT cottinghammatthewg 41bblenhancescd8tcellresponsesinducedbyvectoredvaccinesinmicebutfailstoimproveimmunogenicityinrhesusmacaques
AT hilladrianvs 41bblenhancescd8tcellresponsesinducedbyvectoredvaccinesinmicebutfailstoimproveimmunogenicityinrhesusmacaques