Journal Article

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

Grobusch, Martin P., Bethony, Jeffrey M., Yazdanbakhsh, Maria, Bottazzi, Maria E., Honkpehedji, Yabo J., Massinga Loembe, Marguerite, Betouke Ongwe, Madeleine E., Hotez, Peter J., Kremsner, Peter G., Zinsou, Frejus J., Labuda, Lucja A., van Leeuwen, Remko, Stam, Koen A., Diemert, David J., Dejon Agobe, Jean-Claude, Adegnika, Ayola A., Mouwenda, Yoanne D., Sonnet, Friederike, Jochems, Simon P., De Vries, Sophie

2021

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: 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 / Hookworms / 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