The addition of AfuA and IRP1-3 to the three components aP vaccine improves protection against pertactin-negative B. pertussis infection

FABRICIO MASCHI; ALVAREZ HAYES, JIMENA; MIGUEL AYALA; OVIEDO, JUAN MARCOS; RODRIGUEZ, MARÍA EUGENIA

Buenos Aires

Simposio; 11th International Bordetella Symposium.; 2016

Objetive: In the last few years the incidence of epidemic outbreaks caused by clinical isolates not expressing the only opsonin target antigen included in acellular vaccines, pertactin, drastically increased. We had previously characterized two new opsonin targets expressed during infection, namely AfuA and IRP1-3 that significantly enhanced three component acellular pertussis vaccine (aP) protective capacity against wild type bacteria. These two antigens proved conserved among circulating strains. Objetives: Evaluate whether this new vaccine formulation improves the protection against the newly circulating clinical strain lacking pertactin. Material and Methods: Active protection studies were carried out in BALB/c mice immunized with aP+AfuA+IRP1-3 and challenged with a Prn deficient mutant of B. pertussis (BpΔPrn), a strain that mimics new clinical isolates genotype. Phagocytosis was evaluated by two color microscopic analyses using a confocal laser scanning microscope, and Polymyxin B protection assay was used to evaluate survival of phagocytosed bacteria. Results: We found that antibodies raised against aP+AfuA+IRP1-3 significantly increased the uptake of BpΔPrn by PMN as compared to those induced by aP. We further observed that BpΔPrn strain opsonized with anti-aP+AfuA+IRP1-3 anti-serum were efficiently killed by PMN. Finally, the protective activity of aP+AfuA+IRP1-3 vaccine against infection with BpΔPrn was significantly higher than the protection conferred by aP immunization. Conclusion: Altogether these results suggest that a new generation of aP including AfuA and IRP1-3 will provide higher protection against not only the wild type strain of B. pertussis but also against one of the most distributed new clinical strains.