A glucan-particle based tularemia subunit vaccine induces T-cell immunity and affords partial protection in an inhalation rat infection model

• Published in: PloS one Vol. 19; no. 5; p. e0294998
• Main Authors: Whelan, Adam O, Flick-Smith, Helen C, Walker, Nicola J, Abraham, Ambily, Levitz, Stuart M, Ostroff, Gary R, Oyston, Petra C F
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 07.05.2024
• Subjects: Aerosols; Animals; Antibiotics; Antigens; Antigens, Bacterial - immunology; Bacterial Vaccines - administration & dosage; Bacterial Vaccines - immunology; Biological & chemical terrorism; Biological response modifiers; Biology and Life Sciences; Bioterrorism; Care and treatment; CD4 antigen; CD8 antigen; Disease control; Disease Models, Animal; Dosage and administration; E coli; Female; Francisella tularensis - immunology; Glucan; Glucans; Glucans - immunology; Glucans - pharmacology; Gram-negative bacteria; Health aspects; Imiquimod; Immune response; Immunization; Immunogenicity; Immunology; Infection; Infections; Inhalation; Interferon; Interleukin 17; Lipopolysaccharides; Lymphocytes T; Medical research; Medicine and Health Sciences; Medicine, Experimental; Pathogens; Pharmaceutical research; Physical Sciences; Polysaccharides; Proteins; Rats; Rats, Inbred F344; Research and Analysis Methods; Respiration; T cells; T-Lymphocytes - immunology; Tularemia; Tularemia - immunology; Tularemia - prevention & control; Vaccines; Vaccines, Subunit - administration & dosage; Vaccines, Subunit - immunology; Virulence; Virulence (Microbiology); Yeast; Zoonoses; γ-Interferon; United States; United Kingdom
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0294998

Tularemia is a zoonotic disease caused by the facultative intracellular gram-negative bacterium Francisella tularensis. F. tularensis has a very low infection dose by the aerosol route which can result in an acute, and potentially lethal, infection in humans. Consequently, it is classified as a Category A bioterrorism agent by the US Centers for Disease Control (CDC) and is a pathogen of concern for the International Biodefence community. There are currently no licenced tularemia vaccines. In this study we report on the continued assessment of a tularemia subunit vaccine utilising β-glucan particles (GPs) as a vaccine delivery platform for immunogenic F. tularensis antigens. Using a Fischer 344 rat infection model, we demonstrate that a GP based vaccine comprising the F. tularensis lipopolysaccharide antigen together with the protein antigen FTT0814 provided partial protection of F344 rats against an aerosol challenge with a high virulence strain of F. tularensis, SCHU S4. Inclusion of imiquimod as an adjuvant failed to enhance protective efficacy. Moreover, the level of protection afforded was dependant on the challenge dose. Immunological characterisation of this vaccine demonstrated that it induced strong antibody immunoglobulin responses to both polysaccharide and protein antigens. Furthermore, we demonstrate that the FTT0814 component of the GP vaccine primed CD4+ and CD8+ T-cells from immunised F344 rats to express interferon-γ, and CD4+ cells to express interleukin-17, in an antigen specific manner. These data demonstrate the development potential of this tularemia subunit vaccine and builds on a body of work highlighting GPs as a promising vaccine platform for difficult to treat pathogens including those of concern to the bio-defence community.