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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2019.02497

Intranasal peptide-based FpvA-KLH conjugate vaccine protects mice from Pseudomonas aeruginosa acute murine pneumonia

  • 1Department of MIcrobiology, Immunology, and Cell Biology, West Virginia University, United States
  • 2Vaccine Development Center, West Virginia University School of Medicine, United States

Pseudomonas aeruginosa is an opportunistic pathogen causing acute and chronic respiratory infections associated with morbidity and mortality, especially in patients with cystic fibrosis. Vaccination against P. aeruginosa before colonization may be a solution against these infections and improve the quality of life of at-risk patients. To develop a vaccine against P. aeruginosa, we formulated a novel peptide-based P. aeruginosa subunit vaccine based on the extracellular regions of one of its major siderophore receptors, FpvA. We evaluated the effectiveness and immunogenicity of the FpvA peptides conjugated to keyhole limpet hemocyanin (KLH) with the adjuvant curdlan in a murine vaccination and infection model. Immunization with the FpvA-KLH vaccine decreased the bacterial burden and lung edema after P. aeruginosa challenge. Vaccination with FpvA-KLH lead to antigen-specific IgG and IgM antibodies in sera, and IgA antibodies in lung supernatant. FpvA-KLH immunized mice had an increase in recruitment of CD11b+ dendritic cells as well as resident memory CD4+ T cells in the lungs compared to non-vaccinated challenged mice. Splenocytes isolated from vaccinated animals showed that the FpvA-KLH vaccine with the adjuvant curdlan induces antigen-specific IL-17 production and leads to a Th17 type of immune response. These results indicate that the intranasal FpvA-KLH conjugate vaccine can elicit both mucosal and systemic immune responses. These observations suggest that the intranasal peptide-based FpvA-KLH conjugate vaccine with curdlan is a potential vaccine candidate against P. aeruginosa pneumonia.

Keywords: Pseudomonas aerguinosa, FpvA, Peptide-based vaccines, infection and immunity, Vaccine, Cystic Fibrosis, mucosal immunity, iron acquisition

Received: 13 Jun 2019; Accepted: 07 Oct 2019.

Copyright: © 2019 Sen Kilic, Blackwood, Boehm, Witt, Malkowski, Bevere, Wong, Bradford, Hall, Varney, Damron and Barbier. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Mariette Barbier, West Virginia University, Department of MIcrobiology, Immunology, and Cell Biology, Morgantown, 26506, West Virginia, United States, mabarbier@hsc.wvu.edu