Background and Aims: Subunit vaccines with minimal epitopes are often poorly immunogenic and adjuvants are required to enhance and direct immune responses towards protective determinants. Most pathogens enter or colonise via the upper respiratory tract mucosa. Mucosally active subunit vaccines are an unmet clinical need due to lack of licensed immunostimulants suitable for peptide antigens. It is also critical for a vaccine to be able to stimulate both the humoral and cellular immune system to achieve long-lived protection.
Methods: Mice were immunised intranasally with liposomes incorporating: the Streptococcus pyogenes peptide antigen, J8; diphtheria toxoid as a source of T-cell help; and the immunostimulatory glycolipid, 3D(6-acyl) PHAD® (PHAD) - vaccine referred to as J8-Lipo-DT-PHAD. Antibody responses were assessed by ELISA and cytokine responses were analysed by cytokine bead array (flow cytometry). Gene knock-out mice were utilised to assess specific cell subsets required for vaccination and protection.
Results: We showed that intranasal administration of J8-Lipo-DT-PHAD, was able to induce both cellular and humoral immunity. We demonstrated long-lived humoral and cellular memory responses following vaccination. However, mice genetically deficient in either mucosal antibodies or total antibodies were protected against mucosal infection. By using IL-17-deficient mice or by depleting cellular subsets using antibody therapy, we showed that it is the cellular responses encompassing, CD4+ T-cells, IL-17 and macrophages that play the critical role in vaccine-mediated mucosal immunity.
Conclusions and Significance/Impact: Overall, the data demonstrate the utility of a novel mucosal vaccine platform to deliver multi-pronged protective responses against a highly virulent pathogen.