Airway delivery of both a BCG prime and adenoviral boost drives CD4 and CD8 T cells into the lung tissue parenchyma

Abstract

Heterologous BCG prime-boost regimens represent a promising strategy for an urgently required improved tuberculosis vaccine. Identifying the mechanisms which underpin the enhanced protection induced by such strategies is one key aim which would significantly accelerate rational vaccine development. Experimentally, airway vaccination induces greater efficacy than parenteral delivery; in both conventional vaccination and heterologous boosting of parenteral BCG immunisation. However, the effect of delivering both the component prime and boost immunisations via the airway is not well known. Here we investigate delivery of both the BCG prime and adenovirus boost vaccination via the airway in a murine model, and demonstrate this approach may be able to improve the protective outcome over parenteral prime/airway boost. Intravascular staining of T cells in the lung revealed that the airway prime regimen induced more antigen-specific multifunctional CD4 and CD8 T cells to the lung parenchyma prior to challenge and indicated the route of both prime and boost to be critical to the location of induced resident T cells in the lung. Further, in the absence of a defined phenotype of vaccine-induced protection to tuberculosis; the magnitude and phenotype of vaccine-specific T cells in the parenchyma of the lung may provide insights into potential correlates of immunity.

Local Pulmonary Immunological Biomarkers in Tuberculosis

“…Delivery of vaccine candidates via aerosol routes has been shown to induce specific mucosal immune components that can be compared across species, with BAL samples from macaques and humans following aerosol MVA85A showing increased levels of antigen-specific cellular immune responses compared to peripheral blood (61)(62)(63). Further detailed mechanistic interrogation of lung-specific immunity is possible in the more tractable murine model (64,65).…”