细菌性传染病疫苗研究进展

通过疫苗免疫来保护易感群体是控制细菌性传染病的一个重要环节,细菌减毒活疫苗减少了疫苗的副反应,同时还考虑到接种疫苗群体的营养和健康状况,能有效侵入和持续刺激机体产生初次免疫应答和再次免疫应答。重组减毒细菌具有能够在体内稳定表达保护性抗原的能力,将一段基因插入到染色体中可提高其稳定性,但一般抗原表达水平较低,不能刺激机体产生强有力的免疫应答,而使用高拷贝数的质粒载体后,选择标记基因的表达水平将远远超过载体维持的需要,增加了重组疫苗中的能量消耗,过度表达的基因产物进一步致弱了疫苗。同时宿主-载体的重组应使外源抗原产生的免疫应答最大化,细菌载体抗原产生的完全免疫应答最小化。

Advance in the Vaccine of Bacterial Infectious Diseases

There is a need to develop vaccines with the potential for global use against bacterial infectious diseases.Attenuated vaccine should be sufficient to decrease the side effects induced by vaccine itself.In this regard,the nutritional status and health of the population to be vaccinated should be considered.The attenuated vaccine should be sufficiently invasive and persistent to stimulate both strong primary and lasting memory immune responses.Stability of protective antigen expression in vivo is essential for recombinant vaccine efficacy.Insertion of genes into the chromosome can increase stability,but the level of antigen expression is generally too low to stimulate an adequate immune response.When a plasmid vector with high copy number is used,the level of expression of the gene encoding the vector-selective marker can be far in excess of that necessary for maintenance of the vector.In these instances,overexpression of such a gene product further attenuates the vaccine,presumably due to the added energy drain on the recombinant vaccine.The recombinant system should also be designed to maximize the immune response to the foreign antigen(s) and minimize the competing immuoe responses to bacterial vector antigens.