Intrapulmonary vaccination with delta-inulin adjuvant stimulates non-polarised chemotactic signalling and diverse cellular interaction

• Published in: Mucosal immunology Vol. 14; no. 3; pp. 762 - 773
• Main Authors: Ferrell, Kia C., Stewart, Erica L., Counoupas, Claudio, Ashhurst, Thomas M., Britton, Warwick J., Petrovsky, Nikolai, Triccas, James A.
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.05.2021; Elsevier Limited
• Subjects: Adjuvants; Adjuvants, Immunologic; Allergology; Animals; Antibodies; Biomedical and Life Sciences; Biomedicine; Chemotactic factors; Female; Gastroenterology; Immunity, Innate; Immunization; Immunology; Inflammation; Inulin; Inulin - analogs & derivatives; Inulin - immunology; Lung - immunology; Lymph nodes; Lymphocyte Activation; Lymphocytes T; Mice; Mice, Inbred C57BL; Mucosa; Mucosal-Associated Invariant T Cells - immunology; Phenotypes; Receptors, Antigen, T-Cell, gamma-delta - metabolism; Respiratory diseases; T-Lymphocytes - immunology; Vaccination; Vaccines; Vaccines - immunology
• ISSN: 1933-0219; 1935-3456
• DOI: 10.1038/s41385-021-00379-6

There is an urgent need for novel vaccination strategies to combat respiratory pathogens. Mucosal vaccine delivery is an attractive option as it directly targets the site of infection; however, preclinical development has been hindered by a lack of suitable mucosal adjuvants and a limited understanding of their immune effects in the lung environment. Herein, we define the early immune events following the intrapulmonary delivery of a vaccine incorporating the adjuvant delta-inulin. Analysis of the early inflammatory response showed vaccine-induced innate cell recruitment to lungs and local lymph nodes (LN) was transient and non-polarised, correlating with an increase in pulmonary chemotactic factors. Use of fluorescently labelled adjuvant revealed widespread tissue dissemination of adjuvant particles, coupled with broad cellular uptake and transit to the lung-draining LN by a range of innate immune cells. Mass cytometric analysis revealed extensive phenotypic changes in innate and adaptive cell subsets induced by vaccination; this included identification of unconventional lymphocytes such as γδ-T cells and MAIT cells that increased following vaccination and displayed an activated phenotype. This study details a comprehensive view of the immune response to intrapulmonary adjuvant administration and provides pre-clinical evidence to support delta-inulin as a suitable adjuvant for pulmonary vaccines.