Alvarez Hayes Jimena, Erben Esteban, Lamberti Yanina, Principi Guido, Maschi Fabricio, Ayala Miguel, Rodriguez Maria Eugenia
CINDEFI (UNLP CONICET La Plata), Facultad de Ciencias Exactas, Universidad Nacional de La Plata, La Plata, Argentina.
Vaccine. 2013 Aug 2;31(35):3543-8. doi: 10.1016/j.vaccine.2013.05.072. Epub 2013 May 31.
Bordetella pertussis is the etiologic agent of whooping cough, an illness whose incidence has been increasing over the last decades. Pertussis reemergence despite high vaccination coverage, together with the recent isolation of circulating strains deficient in some of the vaccine antigens, highlight the need for new vaccines. Proteins induced under physiological conditions, such as those required for nutrient acquisition during infection, might represent good targets for better preventive strategies. By mean of serological proteome analysis we identified two novel antigens of B. pertussis potentially involved in iron acquisition during host colonization. We had previously demonstrated that one of them, designated IRP1-3, is protective against pertussis infection in mice. In the present study, we show that the other antigen, named AfuA (BP1605), is a highly antigenic protein, exposed on the bacterial surface, conserved among clinical isolates and expressed during infection. Immunization of mice with the recombinant AfuA induced opsonophagocytic antibodies which could explain the protection against B. pertussis infection conferred by mice immunization with rAfuA. Importantly, we found that the addition of rAfuA and rIRP1-3 proteins to the commercial three pertussis components acellular vaccine significantly increased its protective activity. Taken together, our results point at these two antigens as potential components of a new generation of acellular vaccines.
百日咳博德特氏菌是百日咳的病原体,在过去几十年中,百日咳的发病率一直在上升。尽管疫苗接种覆盖率很高,但百日咳仍再度出现,再加上最近分离出一些缺乏某些疫苗抗原的流行菌株,凸显了研发新型疫苗的必要性。在生理条件下诱导产生的蛋白质,例如感染期间获取营养所需的蛋白质,可能是更好的预防策略的良好靶点。通过血清学蛋白质组分析,我们鉴定出百日咳博德特氏菌的两种新型抗原,它们可能在宿主定殖过程中参与铁的获取。我们之前已经证明,其中一种名为IRP1-3的抗原对小鼠百日咳感染具有保护作用。在本研究中,我们表明另一种名为AfuA(BP1605)的抗原是一种高度抗原性的蛋白质,暴露于细菌表面,在临床分离株中保守,并且在感染期间表达。用重组AfuA免疫小鼠可诱导调理吞噬抗体,这可以解释用rAfuA免疫小鼠对百日咳博德特氏菌感染的保护作用。重要的是,我们发现将rAfuA和rIRP1-3蛋白添加到市售的三种百日咳组分无细胞疫苗中可显著提高其保护活性。综上所述,我们的结果表明这两种抗原是新一代无细胞疫苗的潜在组分。