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

• Published in: PLoS neglected tropical diseases Vol. 15; no. 10; p. e0009732
• Main Authors: Mouwenda, Yoanne D, Betouke Ongwe, Madeleine E, Sonnet, Friederike, Stam, Koen A, Labuda, Lucja A, De Vries, Sophie, Grobusch, Martin P, Zinsou, Frejus J, Honkpehedji, Yabo J, Dejon Agobe, Jean-Claude, Diemert, David J, van Leeuwen, Remko, Bottazzi, Maria E, Hotez, Peter J, Kremsner, Peter G, Bethony, Jeffrey M, Jochems, Simon P, Adegnika, Ayola A, Massinga Loembe, Marguerite, Yazdanbakhsh, Maria
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.10.2021; Public Library of Science (PLoS)
• Subjects: Adjuvants, Immunologic - administration & dosage; Adult; Adults; Ancylostomatoidea - genetics; Ancylostomatoidea - immunology; Animals; Antibodies; Antibodies, Helminth - immunology; Antibody Formation; Antigens; Antigens, Helminth - administration & dosage; Antigens, Helminth - genetics; Antigens, Helminth - immunology; Biology and Life Sciences; CD4 antigen; CD40 antigen; Cells; Clinical trials; CTLA-4 Antigen - genetics; CTLA-4 Antigen - immunology; CTLA-4 protein; Cytokines; Cytometry; Disease control; Drug dosages; Enzymes; Female; Gabon; Health aspects; Health care; Hepatitis B; Hookworm disease; Hookworm Infections - immunology; Hookworm Infections - parasitology; Hookworm Infections - prevention & control; Humans; IgG antibody; Immune response; Immunity, Cellular; Immunogenicity; Immunoglobulin G; Immunological memory; Infections; Interleukin 2; Laboratories; Lipid A; Lipids; Lymphocytes; Lymphocytes T; Male; Medicine and Health Sciences; Memory cells; Middle Aged; Molecules; Parasite vaccines; Parasites; Prevention; Recombinants; T cells; T-Lymphocytes - immunology; Testing; Tropical diseases; Tumor necrosis factor; Vaccination; Vaccines; Vaccines - administration & dosage; Vaccines - genetics; Vaccines - immunology; Young Adult; Gabon; Brazil; United States > US
• ISSN: 1935-2735; 1935-2727; 1935-2735
• DOI: 10.1371/journal.pntd.0009732

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.