Characterization of T cell responses to co-administered hookworm vaccine candidates Na-GST-1 and Na-APR-1 in healthy adults in Gabon.
Two hookworm vaccine candidates, Na-GST-1 and Na-APR-1, formulated with Glucopyranosyl Lipid A (GLA-AF) adjuvant, have been shown to be safe, well tolerated, and to induce antibody responses in a Phase 1 clinical trial (Clinicaltrials.gov NCT02126462) conducted in Gabon. Here, we characterized T cel...
Published in: | PLOS Neglected Tropical Diseases |
---|---|
Main Authors: | , , , , , , , , , , , , , , , , , , , |
Format: | Article in Journal/Newspaper |
Language: | English |
Published: |
Public Library of Science (PLoS)
2021
|
Subjects: | |
Online Access: | https://doi.org/10.1371/journal.pntd.0009732 https://doaj.org/article/74b241e8340f43ffaff17b49d024c36c |
id |
ftdoajarticles:oai:doaj.org/article:74b241e8340f43ffaff17b49d024c36c |
---|---|
record_format |
openpolar |
spelling |
ftdoajarticles:oai:doaj.org/article:74b241e8340f43ffaff17b49d024c36c 2023-05-15T15:14:42+02:00 Characterization of T cell responses to co-administered hookworm vaccine candidates Na-GST-1 and Na-APR-1 in healthy adults in Gabon. Yoanne D Mouwenda Madeleine E Betouke Ongwe Friederike Sonnet Koen A Stam Lucja A Labuda Sophie De Vries Martin P Grobusch Frejus J Zinsou Yabo J Honkpehedji Jean-Claude Dejon Agobe David J Diemert Remko van Leeuwen Maria E Bottazzi Peter J Hotez Peter G Kremsner Jeffrey M Bethony Simon P Jochems Ayola A Adegnika Marguerite Massinga Loembe Maria Yazdanbakhsh 2021-10-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0009732 https://doaj.org/article/74b241e8340f43ffaff17b49d024c36c EN eng Public Library of Science (PLoS) https://doi.org/10.1371/journal.pntd.0009732 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0009732 https://doaj.org/article/74b241e8340f43ffaff17b49d024c36c PLoS Neglected Tropical Diseases, Vol 15, Iss 10, p e0009732 (2021) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2021 ftdoajarticles https://doi.org/10.1371/journal.pntd.0009732 2022-12-31T12:41:29Z Two hookworm vaccine candidates, Na-GST-1 and Na-APR-1, formulated with Glucopyranosyl Lipid A (GLA-AF) adjuvant, have been shown to be safe, well tolerated, and to induce antibody responses in a Phase 1 clinical trial (Clinicaltrials.gov NCT02126462) conducted in Gabon. Here, we characterized T cell responses in 24 Gabonese volunteers randomized to get vaccinated three times with Na-GST-1 and Na-APR-1 at doses of 30μg (n = 8) or 100μg (n = 10) and as control Hepatitis B (n = 6). Blood was collected pre- and post-vaccination on days 0, 28, and 180 as well as 2-weeks after each vaccine dose on days 14, 42, and 194 for PBMCs isolation. PBMCs were stimulated with recombinant Na-GST-1 or Na-APR-1, before (days 0, 28 and 180) and two weeks after (days 14, 42 and 194) each vaccination and used to characterize T cell responses by flow and mass cytometry. A significant increase in Na-GST-1 -specific CD4+ T cells producing IL-2 and TNF, correlated with specific IgG antibody levels, after the third vaccination (day 194) was observed. In contrast, no increase in Na-APR-1 specific T cell responses were induced by the vaccine. Mass cytometry revealed that, Na-GST-1 cytokine producing CD4+ T cells were CD161+ memory cells expressing CTLA-4 and CD40-L. Blocking CTLA-4 enhanced the cytokine response to Na-GST-1. In Gabonese volunteers, hookworm vaccine candidate, Na-GST-1, induces detectable CD4+ T cell responses that correlate with specific antibody levels. As these CD4+ T cells express CTLA-4, and blocking this inhibitory molecules resulted in enhanced cytokine production, the question arises whether this pathway can be targeted to enhance vaccine immunogenicity. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 15 10 e0009732 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Yoanne D Mouwenda Madeleine E Betouke Ongwe Friederike Sonnet Koen A Stam Lucja A Labuda Sophie De Vries Martin P Grobusch Frejus J Zinsou Yabo J Honkpehedji Jean-Claude Dejon Agobe David J Diemert Remko van Leeuwen Maria E Bottazzi Peter J Hotez Peter G Kremsner Jeffrey M Bethony Simon P Jochems Ayola A Adegnika Marguerite Massinga Loembe Maria Yazdanbakhsh Characterization of T cell responses to co-administered hookworm vaccine candidates Na-GST-1 and Na-APR-1 in healthy adults in Gabon. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Two hookworm vaccine candidates, Na-GST-1 and Na-APR-1, formulated with Glucopyranosyl Lipid A (GLA-AF) adjuvant, have been shown to be safe, well tolerated, and to induce antibody responses in a Phase 1 clinical trial (Clinicaltrials.gov NCT02126462) conducted in Gabon. Here, we characterized T cell responses in 24 Gabonese volunteers randomized to get vaccinated three times with Na-GST-1 and Na-APR-1 at doses of 30μg (n = 8) or 100μg (n = 10) and as control Hepatitis B (n = 6). Blood was collected pre- and post-vaccination on days 0, 28, and 180 as well as 2-weeks after each vaccine dose on days 14, 42, and 194 for PBMCs isolation. PBMCs were stimulated with recombinant Na-GST-1 or Na-APR-1, before (days 0, 28 and 180) and two weeks after (days 14, 42 and 194) each vaccination and used to characterize T cell responses by flow and mass cytometry. A significant increase in Na-GST-1 -specific CD4+ T cells producing IL-2 and TNF, correlated with specific IgG antibody levels, after the third vaccination (day 194) was observed. In contrast, no increase in Na-APR-1 specific T cell responses were induced by the vaccine. Mass cytometry revealed that, Na-GST-1 cytokine producing CD4+ T cells were CD161+ memory cells expressing CTLA-4 and CD40-L. Blocking CTLA-4 enhanced the cytokine response to Na-GST-1. In Gabonese volunteers, hookworm vaccine candidate, Na-GST-1, induces detectable CD4+ T cell responses that correlate with specific antibody levels. As these CD4+ T cells express CTLA-4, and blocking this inhibitory molecules resulted in enhanced cytokine production, the question arises whether this pathway can be targeted to enhance vaccine immunogenicity. |
format |
Article in Journal/Newspaper |
author |
Yoanne D Mouwenda Madeleine E Betouke Ongwe Friederike Sonnet Koen A Stam Lucja A Labuda Sophie De Vries Martin P Grobusch Frejus J Zinsou Yabo J Honkpehedji Jean-Claude Dejon Agobe David J Diemert Remko van Leeuwen Maria E Bottazzi Peter J Hotez Peter G Kremsner Jeffrey M Bethony Simon P Jochems Ayola A Adegnika Marguerite Massinga Loembe Maria Yazdanbakhsh |
author_facet |
Yoanne D Mouwenda Madeleine E Betouke Ongwe Friederike Sonnet Koen A Stam Lucja A Labuda Sophie De Vries Martin P Grobusch Frejus J Zinsou Yabo J Honkpehedji Jean-Claude Dejon Agobe David J Diemert Remko van Leeuwen Maria E Bottazzi Peter J Hotez Peter G Kremsner Jeffrey M Bethony Simon P Jochems Ayola A Adegnika Marguerite Massinga Loembe Maria Yazdanbakhsh |
author_sort |
Yoanne D Mouwenda |
title |
Characterization of T cell responses to co-administered hookworm vaccine candidates Na-GST-1 and Na-APR-1 in healthy adults in Gabon. |
title_short |
Characterization of T cell responses to co-administered hookworm vaccine candidates Na-GST-1 and Na-APR-1 in healthy adults in Gabon. |
title_full |
Characterization of T cell responses to co-administered hookworm vaccine candidates Na-GST-1 and Na-APR-1 in healthy adults in Gabon. |
title_fullStr |
Characterization of T cell responses to co-administered hookworm vaccine candidates Na-GST-1 and Na-APR-1 in healthy adults in Gabon. |
title_full_unstemmed |
Characterization of T cell responses to co-administered hookworm vaccine candidates Na-GST-1 and Na-APR-1 in healthy adults in Gabon. |
title_sort |
characterization of t cell responses to co-administered hookworm vaccine candidates na-gst-1 and na-apr-1 in healthy adults in gabon. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2021 |
url |
https://doi.org/10.1371/journal.pntd.0009732 https://doaj.org/article/74b241e8340f43ffaff17b49d024c36c |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 15, Iss 10, p e0009732 (2021) |
op_relation |
https://doi.org/10.1371/journal.pntd.0009732 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0009732 https://doaj.org/article/74b241e8340f43ffaff17b49d024c36c |
op_doi |
https://doi.org/10.1371/journal.pntd.0009732 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
15 |
container_issue |
10 |
container_start_page |
e0009732 |
_version_ |
1766345127793524736 |