Pizza M, Covacci A, Bartoloni A, Perugini M, Nencioni L, De Magistris M T, Villa L, Nucci D, Manetti R, Bugnoli M
Sclavo Research Center, Siena, Italy.
Science. 1989 Oct 27;246(4929):497-500. doi: 10.1126/science.2683073.
Immunization with chemically detoxified pertussis toxin can prevent severe whooping cough with an efficacy similar to that of the cellular pertussis vaccine, which normally gives unwanted side effects. To avoid the reversion to toxicity and the loss of immunogenicity that may follow chemical treatment of pertussis toxin, inactive toxins were constructed by genetic manipulation. A number of genetically engineered alleles of the pertussis toxin genes, constructed by replacing either one or two key amino acids within the enzymatically active S1 subunit, were introduced into the chromosome of strains of Bordetella pertussis, B. parapertussis, and B. bronchiseptica. These strains produce mutant pertussis toxin molecules that are nontoxic and immunogenic and that protect mice from the intracerebral challenge with virulent Bordetella pertussis. Such molecules are ideal for the development of new and safer vaccines against whooping cough.
用化学解毒的百日咳毒素进行免疫接种可预防严重的百日咳，其效果与细胞百日咳疫苗相似，而细胞百日咳疫苗通常会产生不良副作用。为避免化学处理百日咳毒素后可能出现的毒性逆转和免疫原性丧失，通过基因操作构建了无活性毒素。通过替换酶活性S1亚基内的一个或两个关键氨基酸构建的许多百日咳毒素基因的基因工程等位基因，被引入百日咳博德特氏菌、副百日咳博德特氏菌和支气管败血博德特氏菌菌株的染色体中。这些菌株产生无毒且具有免疫原性的突变百日咳毒素分子，可保护小鼠免受强毒百日咳博德特氏菌的脑内攻击。此类分子是开发新型、更安全的百日咳疫苗的理想选择。
