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

Abstract

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.

Biopolymers and Osmolytes — A Focus towards the Prospects of Stability and Adjuvanticity of Vaccines

“…Thus delta-inulin's potential as an adjuvant for lung vaccinations is again supported by this preclinical study. 63 Human clinical trials using delta inulin as adjuvant against hepatitis B 64 and influenza vaccine 65 have also been reported to be successful in providing safety, immunogenicity, and tolerability for even infants and children between ages 6 months and 9 years, supporting the objective of this review. Apart from delta inulin, another crystalline type of inulin called the gamma inulin (γ-inulin) has also shown adjuvant activity.…”

Mucosal immunization with a delta-inulin adjuvanted recombinant spike vaccine elicits lung-resident immune memory and protects mice against SARS-CoV-2

“…Lungs and lymph nodes were processed as described previously 17 . Intravascular staining was performed by the intravascular injection of 15 µg/mL CD45-biotin (clone 30-F11, BioLegend, CA, USA) three minutes before euthanasia.…”

“…We have previously demonstrated that intrapulmonary vaccination with a subunit tuberculosis vaccine formulated with the particulate polysaccharide adjuvant Advax TM generates robust resident memory T cells (TRMs) in the lungs along with systemic antibody responses 16 . The early pulmonary immune response to this vaccine is characterized by a broad chemotactic response that does not result in lasting inflammation 17 . While intranasal administration models are widely used, we selected the intrapulmonary route due to several reasons.…”

Virulence Mechanisms of Mycobacterium abscessus: Current Knowledge and Implications for Vaccine Design

“…Given this is thought to be an immune correlate of protection against M. abscessus , these adjuvants may be useful components of an M. abscessus vaccine. Appropriate selection of adjuvant (such as one with a minimal inflammatory profile) may also facilitate non-parenteral vaccine administration, such as vaccine delivery directly to the respiratory mucosa ( Ferrell et al, 2021 ). There is renewed interest in pulmonary vaccination for TB, whereby delivery of the vaccine directly to the lung induces tissue-resident populations capable of rapid response to M. tb ( Counoupas et al, 2020 ).…”