Characterization of T cell responses to co-administered hookworm vaccine candidates Na-GST-1 and Na-APR-1 in healthy adults in Gabon.

• Main Authors: Yoanne D Mouwenda (Author), Madeleine E Betouke Ongwe (Author), Friederike Sonnet (Author), Koen A Stam (Author), Lucja A Labuda (Author), Sophie De Vries (Author), Martin P Grobusch (Author), Frejus J Zinsou (Author), Yabo J Honkpehedji (Author), Jean-Claude Dejon Agobe (Author), David J Diemert (Author), Remko van Leeuwen (Author), Maria E Bottazzi (Author), Peter J Hotez (Author), Peter G Kremsner (Author), Jeffrey M Bethony (Author), Simon P Jochems (Author), Ayola A Adegnika (Author), Marguerite Massinga Loembe (Author), Maria Yazdanbakhsh (Author)
• Format: Book
• Published: Public Library of Science (PLoS), 2021-10-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

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.

Item Description

1935-2727
1935-2735
10.1371/journal.pntd.0009732