In:
PLOS Neglected Tropical Diseases, Public Library of Science (PLoS), Vol. 15, No. 10 ( 2021-10-1), p. e0009732-
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
1935-2735
DOI:
10.1371/journal.pntd.0009732
DOI:
10.1371/journal.pntd.0009732.g001
DOI:
10.1371/journal.pntd.0009732.g002
DOI:
10.1371/journal.pntd.0009732.g003
DOI:
10.1371/journal.pntd.0009732.g004
DOI:
10.1371/journal.pntd.0009732.t001
DOI:
10.1371/journal.pntd.0009732.s001
DOI:
10.1371/journal.pntd.0009732.s002
DOI:
10.1371/journal.pntd.0009732.s003
DOI:
10.1371/journal.pntd.0009732.s004
DOI:
10.1371/journal.pntd.0009732.s005
DOI:
10.1371/journal.pntd.0009732.s006
DOI:
10.1371/journal.pntd.0009732.s007
DOI:
10.1371/journal.pntd.0009732.s008
DOI:
10.1371/journal.pntd.0009732.r001
DOI:
10.1371/journal.pntd.0009732.r002
DOI:
10.1371/journal.pntd.0009732.r003
DOI:
10.1371/journal.pntd.0009732.r004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2429704-5
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