Moscoso Miriam, Vallejo Juan A, Cabral Maria P, García Patricia, Fuentes-Valverde Víctor, Gato Eva, Arca-Suárez Jorge, Aja-Macaya Pablo, Bou Germán
Department of Microbiology, University Hospital A Coruña (CHUAC)-Biomedical Research Institute A Coruña (INIBIC), 15006 A Coruña, Spain.
Technical Services Department, CZ Vaccines S.A.U., 36400 O Porriño, Pontevedra, Spain.
Vaccines (Basel). 2022 Jun 16;10(6):953. doi: 10.3390/vaccines10060953.
The development of a whole-cell vaccine from bacteria auxotrophic for D-amino acids present in the bacterial cell wall is considered a promising strategy for providing protection against bacterial infections. Here, we constructed a prototype vaccine, consisting of a glutamate racemase-deficient mutant, for preventing infections. The deletion mutant lacks the gene and requires exogenous addition of D-glutamate for growth. The results showed that the Δ strain is attenuated and includes a favourable combination of antigens for inducing a robust immune response and conferring an adequate level of cross-protection against systemic infections caused by strains, including some hypervirulent serotypes with elevated production of capsule polysaccharide as well as multiresistant strains. The auxotroph also induced specific production of IL-17A and IFN-γ. The rapid elimination of the strain from the blood of mice without causing disease suggests a high level of safety for administration as a vaccine.
利用对细菌细胞壁中存在的D-氨基酸营养缺陷型的细菌开发全细胞疫苗,被认为是提供针对细菌感染保护的一种有前景的策略。在此,我们构建了一种由谷氨酸消旋酶缺陷型突变体组成的原型疫苗,用于预防感染。该缺失突变体缺乏该基因,生长需要外源添加D-谷氨酸。结果表明,Δ菌株减毒,包含诱导强烈免疫反应和对由菌株引起的全身感染提供足够水平交叉保护的有利抗原组合,这些菌株包括一些具有高产量荚膜多糖的高毒力血清型以及多重耐药菌株。该营养缺陷型还诱导了IL-17A和IFN-γ的特异性产生。该菌株在小鼠血液中迅速清除而不引起疾病,表明作为疫苗给药具有高度安全性。