TWO NEW ANTIGENS IMPROVE ACELLULAR PERTUSSIS VACCINES EFFICACY AGAINST NOVEL CIRCULATING B. PERTUSSIS STRAINS

JIMENA ALVAREZ HAYES; GERÓNIMO PERAZZO; MARIA EUGENIA RODRIGUEZ

Mar del Plata

Congreso; LIX REUNIÓN CIENTÍFICA ANUAL Sociedad Argentina de Investigación Clínica LXII REUNIÓN ANUAL Sociedad Argentina de Inmunología; 2014

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