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Article

Innate and Adaptive Immune Responses against Bordetella pertussis and Pseudomonas aeruginosa in a Murine Model of Mucosal Vaccination against Respiratory Infection

West Virginia University Vaccine Development Center, Department of Microbiology, Immunology and Cell Biology, 64 Medical Center Drive, Morgantown, WV 26505, USA
*
Author to whom correspondence should be addressed.
The authors contributed equally.
Current affiliation: Marshall University, Department of Pharmaceutical Science and Research, One John Marshall Drive, Huntington, WV 25755, USA.
Vaccines 2020, 8(4), 647; https://doi.org/10.3390/vaccines8040647
Received: 28 September 2020 / Revised: 23 October 2020 / Accepted: 28 October 2020 / Published: 3 November 2020
(This article belongs to the Special Issue Next-Generation Pertussis Vaccines)
Whole cell vaccines are frequently the first generation of vaccines tested for pathogens and can inform the design of subsequent acellular or subunit vaccines. For respiratory pathogens, administration of vaccines at the mucosal surface can facilitate the generation of a localized mucosal immune response. Here, we examined the innate and vaccine-induced immune responses to infection by two respiratory pathogens: Bordetella pertussis and Pseudomonas aeruginosa. In a model of intranasal administration of whole cell vaccines (WCVs) with the adjuvant curdlan, we examined local and systemic immune responses following infection. These studies showed that intranasal vaccination with a WCV led to a reduction of the bacterial burden in the airways of animals infected with the respective pathogen. However, there were unique changes in the cytokines produced, cells recruited, and inflammation at the site of infection. Both mucosal vaccinations induced antibodies that bind the target pathogen, but linear regression and principal component analysis revealed that protection from these pathogens is not solely related to antibody titer. Protection from P. aeruginosa correlated to a reduction in lung weight, blood lymphocytes and neutrophils, and the cytokines IL-6, TNF-α, KC/GRO, and IL-10, and promotion of serum IgG antibodies and the cytokine IFN-γ in the lung. Protection from B. pertussis infection correlated strongly with increased anti-B-pertussis serum IgG antibodies. These findings reveal valuable correlates of protection for mucosal vaccination that can be used for further development of both B. pertussis and P. aeruginosa vaccines. View Full-Text
Keywords: vaccination; vaccine development; whooping cough; pneumonia; Pseudomonas aeruginosa; Bordetella pertussis; whole cell vaccine; intranasal; mucosal vaccination; vaccine development; whooping cough; pneumonia; Pseudomonas aeruginosa; Bordetella pertussis; whole cell vaccine; intranasal; mucosal
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MDPI and ACS Style

Blackwood, C.B.; Sen-Kilic, E.; Boehm, D.T.; Hall, J.M.; Varney, M.E.; Wong, T.Y.; Bradford, S.D.; Bevere, J.R.; Witt, W.T.; Damron, F.H.; Barbier, M. Innate and Adaptive Immune Responses against Bordetella pertussis and Pseudomonas aeruginosa in a Murine Model of Mucosal Vaccination against Respiratory Infection. Vaccines 2020, 8, 647. https://doi.org/10.3390/vaccines8040647

AMA Style

Blackwood CB, Sen-Kilic E, Boehm DT, Hall JM, Varney ME, Wong TY, Bradford SD, Bevere JR, Witt WT, Damron FH, Barbier M. Innate and Adaptive Immune Responses against Bordetella pertussis and Pseudomonas aeruginosa in a Murine Model of Mucosal Vaccination against Respiratory Infection. Vaccines. 2020; 8(4):647. https://doi.org/10.3390/vaccines8040647

Chicago/Turabian Style

Blackwood, Catherine B., Emel Sen-Kilic, Dylan T. Boehm, Jesse M. Hall, Melinda E. Varney, Ting Y. Wong, Shelby D. Bradford, Justin R. Bevere, William T. Witt, F. H. Damron, and Mariette Barbier. 2020. "Innate and Adaptive Immune Responses against Bordetella pertussis and Pseudomonas aeruginosa in a Murine Model of Mucosal Vaccination against Respiratory Infection" Vaccines 8, no. 4: 647. https://doi.org/10.3390/vaccines8040647

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