Journal Article

A phase I trial evaluating the safety and immunogenicity of a candidate tuberculosis vaccination regimen, ChAdOx1 85A prime – MVA85A boost in healthy UK adults

Stockdale, Lisa, Davenne, Tamara, Minhinnick, Alice, Lawrie, Alison, Wilkie, Morven, Ramon, Raquel Lopez, Morton, Joshua, Moss, Paul, Hamidi, Ali, O'Shea, Matthew K., Satti, Iman, Harris, Stephanie, Riste, Michael, Dwivedi, Kritica, Behrens, Hannah Michaela, Vermaak, Samantha, Sheehan, Sharon, Wright, Daniel, Thomas, Zita-Rose Manjaly, McShane, Helen

2020

Overview

This phase I trial evaluated the safety and immunogenicity of a candidate tuberculosis vaccination regimen, ChAdOx1 85A prime-MVA85A boost, previously demonstrated to be protective in animal studies, in healthy UK adults. We enrolled 42 healthy, BCG-vaccinated adults into 4 groups: low dose Starter Group (n = 6; ChAdOx1 85A alone), high dose groups; Group A (n = 12; ChAdOx1 85A), Group B (n = 12; ChAdOx1 85A prime – MVA85A boost) or Group C (n = 12; ChAdOx1 85A – ChAdOx1 85A prime – MVA85A boost). Safety was determined by collection of solicited and unsolicited vaccine-related adverse events (AEs). Immunogenicity was measured by antigen-specific ex-vivo IFN-γ ELISpot, IgG serum ELISA, and antigen-specific intracellular IFN-γ, TNF-α, IL-2 and IL-17. AEs were mostly mild/moderate, with no Serious Adverse Events. ChAdOx1 85A induced Ag85A-specific ELISpot and intracellular cytokine CD4+ and CD8+ T cell responses, which were not boosted by a second dose, but were boosted with MVA85A. Polyfunctional CD4+ T cells (IFN-γ, TNF-α and IL-2) and IFN-γ+, TNF-α+ CD8+ T cells were induced by ChAdOx1 85A and boosted by MVA85A. ChAdOx1 85A induced serum Ag85A IgG responses which were boosted by MVA85A. A ChAdOx1 85A prime – MVA85A boost is well tolerated and immunogenic in healthy UK adults.

• Publisher: Elsevier Ltd,Elsevier Limited,Elsevier Science
• Subject: Adult / Adults / Allergy and Immunology / Amino acids / Antigens / Bacillus Calmette-Guerin vaccine / BCG / BCG Vaccine - administration & dosage / BCG Vaccine - immunology / blood serum / CD4 antigen / CD4-positive T-lymphocytes / CD4-Positive T-Lymphocytes - immunology / CD8 antigen / CD8-positive T-lymphocytes / CD8-Positive T-Lymphocytes - immunology / ChAdOx1 85A / Clinical trials / Cytokines / Cytokines - immunology / Drug dosages / Enzyme-linked immunosorbent assay / Evaluation / Follow-Up Studies / Good Manufacturing Practice / Hepatitis / Humans / Immunization / Immunization, Secondary / Immunogenicity / Immunogenicity, Vaccine / Immunoglobulin G / Immunoglobulins / interferon-gamma / Interleukin 17 / Interleukin 2 / Intracellular / Lymphocytes / Lymphocytes T / MVA85A / Peptides / Proteins / Safety / Tuberculosis / Tuberculosis - immunology / Tuberculosis - prevention & control / Tuberculosis Vaccines - administration & dosage / Tuberculosis Vaccines - adverse effects / Tuberculosis Vaccines - immunology / tumor necrosis factor-alpha / Tumor necrosis factor-α / United Kingdom / Vaccination / Vaccination - adverse effects / Vaccination - methods / Vaccine / Vaccines / Volunteers / γ-Interferon