Salmonella enterica serovar Typhi live vector vaccines finally come of age.
Salmonella enterica serovar Typhi live vector vaccines finally come of age.
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DOI：
10.1038/icb.2009.31
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发表时间：
2009-07
影响因子：
4
通讯作者：
Levine, Myron M
中科院分区：
文献类型：
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作者：
Galen, James E;Pasetti, Marcela F;Tennant, Sharon;Ruiz-Olvera, Patricia;Sztein, Marcelo B;Levine, Myron M
减毒细菌疫苗株作为活载体，将来自无关细菌、病毒和寄生虫病原体的外来抗原呈递给免疫系统，具有很大的应用前景。虽然这种方法在实验动物模型中已被证明在诱导抗原特异性黏膜、体液和细胞反应方面相当成功，但到目前为止进行的临床试验结果却令人失望。我们假设，人类对活载体递送的外来抗原反应不佳，这表明迄今为止所使用的菌株和基因方法导致疫苗株过度减毒，免疫原性严重降低。然而，目前在外来抗原表达的遗传学、对活载体免疫机制的理解以及免疫策略的改进方面已经取得了显著进展。现在是开发多价活载体的时候了，在多价活载体中，稳定的抗原表达与代谢适应性相平衡，以创造出具有高免疫原性的疫苗。
Attenuated bacterial vaccine strains hold great promise as live vectors for presentation of foreign antigens from unrelated bacterial, viral, and parasitic pathogens to the immune system. While this approach has proven quite successful in experimental animal models for eliciting antigen-specific mucosal, humoral, and cellular responses, results have been disappointing for clinical trials carried out thus far. We hypothesize that the paucity of human responses to foreign antigens delivered by live vectors suggests that the strains and genetic approaches used to date have resulted in over-attenuated vaccine strains with severely reduced immunogenicity. However, remarkable advances have now been made in the genetics of foreign antigen expression, understanding mechanisms of live vector immunity, and refining immunization strategies. The time has now come for development of multivalent live vectors in which stable antigen expression is balanced with metabolic fitness to create highly immunogenic vaccines.