Homologous and heterologous protection after single intranasal administration of live attenuated recombinant Bordetella pertussis

Homologous and heterologous protection after single intranasal administration of live attenuated recombinant Bordetella pertussis
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DOI:
10.1038/nbt0598-454
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发表时间:
1998-05-01
影响因子:
46.9
通讯作者:
Locht, C
Locht, C
中科院分区:
工程技术1区
文献类型:
--
作者:
Mielcarek, N;Riveau, G;Locht, C

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虽然单剂量粘膜免疫最好通过使用减毒活微生物来实现,但减毒通常导致免疫原性降低。我们通过缺失百日咳毒素基因来减毒百日咳博德特氏菌。该菌株的单次鼻内给药保护了随后的攻击,与亲本菌株一样,并且比用商业疫苗免疫更好。出乎意料的是,这种减毒导致针对保护性抗原丝状血凝素(FHA)的免疫原性增加。此外,针对与FHA基因融合的曼氏血吸虫Sm28GST的免疫原性也得到增强,从而产生针对寄生虫的保护作用,其特征在于单次鼻内给药后蠕虫负荷和卵电荷减少。因此,减毒重组B.百日咳菌株是通过单次鼻内给药同时保护免受百日咳和异源疾病的有希望的载体。
While single-dose mucosal immunization is best achieved by the use of attenuated live microorganisms, attenuation generally results in decreased immunogenicity. We attenuated Bordetella pertussis by the deletion of the pertussis toxin gene. A single intranasal administration of this strain protected against subsequent challenge as well as did the parent strain and better than immunization with commercial vaccine. Unexpectedly, this attenuation resulted in increased immunogenicity against the protective antigen filamentous hemagglutinin (FHA). In addition, immunogenicity was also enhanced against the Schistosoma mansoni Sm28GST genetically fused to FHA, resulting in protection against the parasite, as characterized by a reduction in worm burden and egg charge, after a single intranasal administration. Thus, attenuated recombinant B. pertussis strains are promising vectors for the simultaneous protection against pertussis and heterologous diseases by a single intranasal administration.