Pertussis vaccine efficacy against old and novel circulating bacteria can be improved by the addition of two new vaccine candidates

RODRIGUEZ, MARIA EUGENIA

Baltimore

Conferencia; International Conference on Vaccines. Research & Development; 2015

United Scientific Group

Bordetella pertussis (Bp) is the etiologic agent of whooping cough, the most prevalent vaccine-preventabledisease. Current acellular pertussis vaccines (aP) are formulated with different combination of Bp virulence factors suchas pertactin (Prn) among others. Probably due to vaccine immune selection, during the last few years clinical isolatesnot expressing Prn have been causing epidemic outbreaks. While Prn is not critical for infection, it is the only antigenpresent in Pa able to raise opsonophagocytic antibodies, a key protecting activity against Bp infection. Thus, the additionof new opsonin targets is increasingly needed to improve current vaccines. Recently, we characterized two newantigens, namely AfuA and IRP1-3, which are already in preclinical studies of pertussis vaccines. These two antigensare particularly interesting since they induce opsonic antibodies that increase significantly Pa protective capacity. In thepresent study we investigated whether this new vaccine formulation might be also more effective against this newlycirculating clinical strain. By mean of flow cytometry and fluorescence microscopy we found that, as compared withanti-aP anti-serum, opsonization with serum from mice vaccinated with aP+AfuA+IRP1-3 (aP*) significantly increasedPMN phagocytosis of a Prn deficient mutant of Bp (Bp?Prn), a strain that mimics new clinical isolates genotype.Polymyxin B protection assay showed that bacteria opsonized with anti-aP* anti-serum were efficiently killed by PMN.Finally, we evaluated the ability of aP* vaccine to protect mice against infection with Bp?Prn. We observed a significantincrease in the protection level when mice were immunized with aP* as compared with aP immunization (p