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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2021-10-01
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| Series: | PLoS Neglected Tropical Diseases |
| Online Access: | https://doi.org/10.1371/journal.pntd.0009732 |
| _version_ | 1819099305334538240 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-22T00:44:46Z |
| format | Article |
| id | doaj.art-74b241e8340f43ffaff17b49d024c36c |
| institution | Directory Open Access Journal |
| issn | 1935-2727 1935-2735 |
| language | English |
| last_indexed | 2024-12-22T00:44:46Z |
| publishDate | 2021-10-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Neglected Tropical Diseases |
| spelling | doaj.art-74b241e8340f43ffaff17b49d024c36c2022-12-21T18:44:35ZengPublic Library of Science (PLoS)PLoS Neglected Tropical Diseases1935-27271935-27352021-10-011510e000973210.1371/journal.pntd.0009732Characterization of T cell responses to co-administered hookworm vaccine candidates Na-GST-1 and Na-APR-1 in healthy adults in Gabon.Yoanne D MouwendaMadeleine E Betouke OngweFriederike SonnetKoen A StamLucja A LabudaSophie De VriesMartin P GrobuschFrejus J ZinsouYabo J HonkpehedjiJean-Claude Dejon AgobeDavid J DiemertRemko van LeeuwenMaria E BottazziPeter J HotezPeter G KremsnerJeffrey M BethonySimon P JochemsAyola A AdegnikaMarguerite Massinga LoembeMaria YazdanbakhshTwo 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.https://doi.org/10.1371/journal.pntd.0009732 |
| spellingShingle | 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. PLoS Neglected Tropical Diseases |
| 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_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_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_sort | characterization of t cell responses to co administered hookworm vaccine candidates na gst 1 and na apr 1 in healthy adults in gabon |
| url | https://doi.org/10.1371/journal.pntd.0009732 |
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