Intranasal challenge with B. pertussis leads to more severe disease manifestations in mice than aerosol challenge

Abstract

The murine Bordetella pertussis challenge model has been utilized in preclinical research for decades. Currently, inconsistent methodologies are employed by researchers across the globe, making it difficult to compare findings. The objective of this work was to utilize the CD-1 mouse model with two routes of challenge, intranasal and aerosol administration of B. pertussis, to understand the differences in disease manifestation elicited via each route. We observed that both routes of B. pertussis challenge result in dose-dependent colonization of the respiratory tract, but overall, intranasal challenge led to higher bacterial burden in the nasal lavage, trachea, and lung. Furthermore, high dose intranasal challenge results in induction of leukocytosis and pro-inflammatory cytokine responses compared to aerosol challenge. These data highlight crucial differences in B. pertussis challenge routes that should be considered during experimental design.

BECC438b TLR4 agonist supports unique immune response profiles from nasal and muscular DTaP pertussis vaccines in murine challenge models

“…The aerosol challenge model of B. pertussis , as an alternative, utilizes an aerosolization chamber and nebulizes the dose of bacteria so that it is inhaled and more closely mimics natural exposure. Our lab, in developing this protocol, has observed lower bacterial burden in the lung, nasal lavage, and trachea of naïve mice after aerosol challenge than those challenged by liquid inoculum ( 59 , 67 ). To build upon the results of Fig.…”

“…Existing aP pertussis vaccines (DTaP and Tdap) are adjuvanted with alum which is known to induce a Th2-dominant humoral immune response ( 7 , 9 , 66 – 68 ). In B. pertussis infections, the functionality of antibodies is paramount for preventing adhesion of the bacterium, upon infection, to the respiratory epithelium in addition to neutralizing toxins ( 69 – 72 ).…”

“…Also, we only utilized one time point post challenge: 3 days. Our lab has previously showed that the 3-day-post-challenge timepoint regardless of aerosolization or intranasal instillation corresponds to a peak in bacterial burden in disease-relevant tissues ( 66 , 67 ). This does not necessarily correlate to peaks in antibody or cellular responses which may grow with time.…”