Development of a thermostable spray dried outer membrane vesicle pertussis vaccine for pulmonary immunization

Abstract

Worldwide resurgence of whooping cough calls for improved, next-generation pertussis vaccines that induce broad and long-lasting immunity. A mucosal pertussis vaccine based on outer membrane vesicles (omvPV) is a promising candidate. Further, a vaccine that is stable outside the cold chain would be of substantial advantage for worldwide distribution and application. A vaccine formulated as a powder could both stabilize the vaccine as well as make it suitable for pulmonary vaccination. To that end, we developed a spray dried omvPV with improved stability compared to the liquid omvPV formulation. Spray drying did not affect the structural integrity of the omvPV. The antigenicity of Vag8, a major antigen in omvPV was diminished slightly and an altered tryptophan fluorescence indicated some changes in protein structure. However, when administered via the pulmonary route in mice after reconstitution, spray dried omvPV showed comparable immune responses and protection against challenge with live B. pertussis as liquid omvPV. Mucosal IgA and Th17 responses were established in addition to broad systemic IgG and Th1/Th17 responses, indicating the induction of an effective immunity profile. Overall, a spray dried omvPV was developed that maintained effective immunogenic properties and has an improved storage stability.

Intranasal immunization with outer membrane vesicle pertussis vaccine confers broad protection through mucosal IgA and Th17 responses

“…Therefore, the current focus for improving pertussis vaccines is on providing longer-lasting immunity, establishing adaptive immune responses against a broader range of antigens to increase the robustness of protection and prevention of transmission by reducing nasal carriage of B. pertussis. www.nature.com/scientificreports www.nature.com/scientificreports/ Earlier we have shown that omvPV induces immune responses against a broad range of antigens, as well as a more Th1/Th17 and less Th2 biased response when administered subcutaneously or in the lungs 13,15,16,21 . In the current study, we compared intranasal and subcutaneous immunization with omvPV from the B1917 strain (summarized in Table 1).…”

“…More research to whether these play a role in longevity of the memory response will be important for future research. www.nature.com/scientificreports www.nature.com/scientificreports/ Previously, we demonstrated that induction of mucosal immunity and faster bacterial clearance from the lungs could be achieved through pulmonary administration of omvPV in both spray dried (reconstituted) and liquid form 15,21 . However, whereas the pulmonary immunization with omvPV led to significant reduction of B. pertussis in the nasal cavity, in the current study we demonstrated that intranasal immunization with omvPV provided complete B. pertussis clearance, also from the nasal cavity of mice.…”

“…Western blotting for antibody profiling. The antibody profiling using SDS-PAGE and Western blotting to characterize serum IgG, pulmonary IgA and nasal IgA to identify immunogenic proteins was performed as described previously 21 . The antigen identification of immunogenic antigens was not done in this study but obtained from a previous study 16 .…”

“…However, despite the excellent induction of systemic responses by systemic omvPV immunization, nasal carriage is not diminished. We recently showed that omvPV can be administrated directly in the respiratory tract leading to faster bacterial clearance from the lungs compared to subcutaneous immunization 15,21 . Pulmonary immunization also resulted in mucosal Th17 cells and IgA that were not present after subcutaneous immunization.…”

Immunomodulation as a Novel Strategy for Prevention and Treatment of Bordetella spp. Infections

“…This spray significantly improves delivery and decreases the discomfort other intranasal formulations might cause. Importantly, this delivery method still maintains all the outstanding qualities of the classical delivery of these purified outer membrane vesicles (300).…”