Influence of Aerosol Delivered BCG Vaccination on Immunological and Disease Parameters Following SARS-CoV-2 Challenge in Rhesus Macaques

Frontiers in Immunology

Julian Hopkin¹  Fergus Gleeson²  Mark Bodman-Smith³  Miriam Moffatt⁴  William Cookson⁴  Colin Churchward⁴  Susan Fotheringham⁵  Laura Sibley⁵  Tom Tipton⁵  Adam Mabbutt⁵  Kevin Bewley⁵  Holly E. Humphries⁵  Konstantinos Gkolfinos⁵  Emma Rayner⁵  Andrew D. White⁵  Alexandra L. Morrison⁵  Laura Hunter⁵  Mike Dennis⁵  Charlotte Sarfas⁵  Yper Hall⁵  Alastair Handley⁵  Miles Carroll⁵  Robert Watson⁵  Sally Sharpe⁵  Francisco J. Salguero⁵  Karen Gooch⁵  Chelsea Kennard⁵  Stephanie Longet⁵  Helen McShane⁶ 

[1] College of Medicine, Institute of Life Science, Swansea University, Swansea, United Kingdom;Department of Oncology, Churchill Hospital, Oxford, United Kingdom;Infection and Immunity Research Institute, St George’s University of London, London, United Kingdom;National Heart and Lung Institute, Imperial College London, London, United Kingdom;Research and Evaluation, United Kingdom Health Security Agency, Salisbury, United Kingdom;The Jenner Institute, University of Oxford, Oxford, United Kingdom;

关键词: Aerosol BCG vaccination;    SARS-CoV-2;    COVID-19;    macaque;    cross-protection;    non-specific;   

DOI  :  10.3389/fimmu.2021.801799

来源: DOAJ

【 摘 要 】

The tuberculosis vaccine, Bacille Calmette-Guerin (BCG), also affords protection against non-tuberculous diseases attributable to heterologous immune mechanisms such as trained innate immunity, activation of non-conventional T-cells, and cross-reactive adaptive immunity. Aerosol vaccine delivery can target immune responses toward the primary site of infection for a respiratory pathogen. Therefore, we hypothesised that aerosol delivery of BCG would enhance cross-protective action against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and be a deployable intervention against coronavirus disease 2019 (COVID-19). Immune parameters were monitored in vaccinated and unvaccinated rhesus macaques for 28 days following aerosol BCG vaccination. High-dose SARS-CoV-2 challenge was applied by intranasal and intrabronchial instillation and animals culled 6–8 days later for assessment of viral, disease, and immunological parameters. Mycobacteria-specific cell-mediated immune responses were detected following aerosol BCG vaccination, but SARS-CoV-2-specific cellular- and antibody-mediated immunity was only measured following challenge. Early secretion of cytokine and chemokine markers associated with the innate cellular and adaptive antiviral immune response was detected following SARS-CoV-2 challenge in vaccinated animals, at concentrations that exceeded titres measured in unvaccinated macaques. Classical CD14+ monocytes and Vδ2 γδ T-cells quantified by whole-blood immunophenotyping increased rapidly in vaccinated animals following SARS-CoV-2 challenge, indicating a priming of innate immune cells and non-conventional T-cell populations. However, viral RNA quantified in nasal and pharyngeal swabs, bronchoalveolar lavage (BAL), and tissue samples collected at necropsy was equivalent in vaccinated and unvaccinated animals, and in-life CT imaging and histopathology scoring applied to pulmonary tissue sections indicated that the disease induced by SARS-CoV-2 challenge was comparable between vaccinated and unvaccinated groups. Hence, aerosol BCG vaccination did not induce, or enhance the induction of, SARS-CoV-2 cross-reactive adaptive cellular or humoral immunity, although an influence of BCG vaccination on the subsequent immune response to SARS-CoV-2 challenge was apparent in immune signatures indicative of trained innate immune mechanisms and primed unconventional T-cell populations. Nevertheless, aerosol BCG vaccination did not enhance the initial clearance of virus, nor reduce the occurrence of early disease pathology after high dose SARS-CoV-2 challenge. However, the heterologous immune mechanisms primed by BCG vaccination could contribute to the moderation of COVID-19 disease severity in more susceptible species following natural infection.

【 授权许可】

Unknown