Summary
Whooping cough, caused by the bacterium Bordetella pertussis, is a vaccine-preventable respiratory disease with high risk for respiratory failure, encephalopathy and death in unvaccinated or incompletely vaccinated infants. Although pertussis vaccination resulted in a dramatic decrease of whooping cough cases, pertussis resurged the last decades even in the vaccinated population, pinpointing the need for improved pertussis vaccines or vaccination strategies. Whereas parenteral vaccination with current acellular pertussis vaccines prevents disease, it fails to block nasopharyngeal carriage and transmission of B. pertussis.
Intranasal vaccination could be a promising strategy to overcome these shortcomings as this allows activation of local mucosal immune tissue in the nasopharynx such as nasopharynx-associated lymphoid tissues (NALT), comprising adenoids and tonsils, which are potent induction sites for natural immunity against upper respiratory pathogens. Located in the strategic anatomical site, NALT are likely to play a critical role in mediating bacterial carriage and its clearance in the nasopharynx. Recent studies in mice showed that intranasal immunization with a non-replicating pertussis vaccine candidate based on outer membrane vesicles (omvPV) prevents B. pertussis colonization in the nose and that the induction of mucosal T-helper 17 cells and IgA antibodies are thought to play an important role.
In this project, we aim to evaluate the capacity of omvPV to induce these mucosal Th17 and IgA responses in an established ex vivo mucosal immune tissue model from humans and thus provide an indicator for this vaccination strategy to induce the desired immunity to block transmission in humans.
Project Outcome
Whooping cough, caused by the bacterium Bordetella pertussis, is a vaccine-preventable respiratory disease with high risk for respiratory failure, encephalopathy and death in unvaccinated or incompletely-vaccinated infants. Although pertussis vaccination resulted in a dramatic decrease of whooping cough cases, pertussis resurged the last decades even in the vaccinated population, pinpointing the need for improved pertussis vaccines or vaccination strategies. Whereas parenteral vaccination with current acellular pertussis vaccines prevents disease, it fails to block nasopharyngeal carriage and transmission of B. pertussis. Intranasal vaccination could be a promising strategy to overcome these shortcomings as this allows activation of local mucosal immune tissue in the nasopharynx such as nasopharynx-associated lymphoid tissues (NALT), comprising adenoids and tonsils, which are potent induction sites for natural immunity against upper respiratory pathogens. Located in the strategic anatomical site, NALT are likely to play a critical role in mediating bacterial carriage and its clearance in the nasopharynx. Recent studies in mice showed that intranasal immunization with a non-replicating pertussis vaccine candidate based on outer membrane vesicles (omvPV) prevents B. pertussis colonization in the nose and that the induction of mucosal T-helper 17 cells and antibodies are thought to play an important role. In this project, we aim to evaluate the capacity of omvPV to induce these mucosal Th17 and anti-pertussis antibody responses in an established ex vivo mucosal immune tissue model from humans and thus provide an indicator for this vaccination strategy to induce the desired immunity to block transmission in humans.
We have shown omvPV, as a candidate pertussis vaccine induce significant T cell response including Th17 cell activation and anti-pertussis antibody responses in human nasopharynx mucosal tissue. This suggests that omvPV may become an effective intranasal spray vaccine preventing pertussis infection in humans.