Intranasal acellular pertussis vaccine provides mucosal immunity and protects mice from Bordetella pertussis
Year: 2019
Type: article
Abstract: Current acellular pertussis vaccines fall short of optimal protection against the human respiratory pathogenBordetella pertussisresulting in increased incidence of a previously controlled vaccine- preventable disease. Natural infection is known to induce a protective mucosal immunity. Therefore, in this study, we aimed to use acellular pertussis vaccines to recapitulate these mucosal immune responses. We utilized a murine immunization and challenge model to characterize the efficacy of intranasal immunization (IN) with DTaP vaccine or DTaP vaccine supplemented with curdlan, a known Th1/Th17 promoting adjuvant. Protection from IN delivered DTaP was compared to protection mediated by intraperitoneal injection of DTaP and whole-cell pertussis vaccines. We tracked fluorescently labeled DTaP after immunization and detected that DTaP localized preferentially in the lungs while DTaP with curdlan was predominantly in the nasal turbinates. IN immunization with DTaP, with or without curdlan adjuvant, resulted in anti-B. pertussisand anti-pertussis toxin IgG titers at the same level as intraperitoneally administered DTaP. IN immunization was able to protect againstB. pertussischallenge and we observed decreased pulmonary pro-inflammatory cytokines, neutrophil infiltrates in the lung, and bacterial burden in the upper and lower respiratory tract at day 3 post challenge. Furthermore, IN immunization with DTaP triggered mucosal immune responses such as production ofB. pertussis-specific IgA, and increased IL-17A. Together, the induction of a mucosal immune response and humoral antibody-mediated protection associated with an IN administered DTaP and curdlan adjuvant warrant further exploration as a pertussis vaccine candidate formulation.
Source: npj Vaccines
Language: English
Subfield: Microbiology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,170
Funders: West Virginia University, West Virginia Higher Education Policy Commission, National Institutes of Health, Cancer Institute, West Virginia University, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, National Center for Research Resources
Awards: G1274820946, G1477239627, G1739031488, G1851004052, G2184926764, G2202983096, G2396016572, CoBRE for Signal Transduction and Cancer Phase III, G3239588317, G3639368626, G3697345368, G3858632547, G4196128219, G474381023, G4761650986, G486607418, G5472205517, G559773446, Special Becton Dickinson Fortessa Flow Cytometer, G6730861485, CoBRE for Signal Transduction and Cancer Phase III, Development of mucosal vaccines to protect against pertussis, G8153345299, G8435548099, G9000038508, G9000106503, G9000133327, G9000161317, West Virginia IDeA Network of Biomedical Research Excellence (WV-INBRE)
OpenAlex ID: W2978155607