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

• Published in: Vaccine 2020-01, Vol.38 (4), p.779-789
• Main Authors: Wilkie, Morven, Satti, Iman, Minhinnick, Alice, Harris, Stephanie, Riste, Michael, Ramon, Raquel Lopez, Sheehan, Sharon, Thomas, Zita-Rose Manjaly, Wright, Daniel, Stockdale, Lisa, Hamidi, Ali, O'Shea, Matthew K., Dwivedi, Kritica, Behrens, Hannah Michaela, Davenne, Tamara, Morton, Joshua, Vermaak, Samantha, Lawrie, Alison, Moss, Paul, McShane, Helen
• Format: Article
• Language: English
• Subjects: Adult; Adults; Amino acids; Antigens; Bacillus Calmette-Guerin vaccine; BCG; BCG Vaccine - administration & dosage; BCG Vaccine - immunology; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; CD8 antigen; 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; 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-α; United Kingdom; Vaccination; Vaccination - adverse effects; Vaccination - methods; Vaccine; Vaccines; Volunteers; γ-Interferon
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2019.10.102

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.