Banerjee Soumalya, Halder Prolay, Das Sanjib, Maiti Suhrid, Bhaumik Ushasi, Dutta Moumita, Chowdhury Goutam, Kitahara Kei, Miyoshi Shin-Ichi, Mukhopadhyay Asish Kumar, Dutta Shanta, Koley Hemanta
Division of Bacteriology, ICMR-National Institute of Cholera and Enteric Diseases, P-33 CIT Road, Scheme-XM, Beliaghata, Kolkata, 700010, India.
Division of Electron Microscopy, ICMR-National Institute of Cholera and Enteric Diseases, P-33 CIT Road, Scheme-XM, Beliaghata, Kolkata, 700010, India.
Immunol Lett. 2023 Nov;263:33-45. doi: 10.1016/j.imlet.2023.09.009. Epub 2023 Sep 19.
Diarrhoeagenic Escherichia coli (DEC) pathotypes are one of the major causative agents of diarrhoea induced childhood morbidity and mortality in developing countries. Licensed vaccines providing broad spectrum protection against DEC mediated infections are not available. Outer membrane vesicles (OMVs) are microvesicles released by gram-negative bacteria during the growth phase and contain multiple immunogenic proteins. Based on prevalence of infections, we have formulated a pentavalent outer-membrane vesicles (POMVs) based immunogen targeting five main pathotypes of DEC responsible for diarrhoeal diseases. Following isolation, OMVs from five DEC pathotypes were mixed in equal proportions to formulate POMVs and 10 µg of the immunogen was intraperitoneally administered to adult BALB/c mice. Three doses of POMVs induced significant humoral immune response against whole cell lysates (WCLs), outer membrane proteins (OMPs) and lipopolysaccharides (LPS) isolated from DEC pathotypes along with significant induction of cellular immune response in adult mice. Passive transfer of POMVs immunized adult mice sera protected neonatal mice significantly against DEC infections. Overall, this study finds POMVs to be immunogenic in conferring broad-spectrum passive protection to neonatal mice against five main DEC pathotypes. Altogether, these findings suggest that POMVs can be used as a potent vaccine candidate to ameliorate the DEC-mediated health burden.
致泻性大肠杆菌(DEC)致病型是发展中国家儿童腹泻所致发病和死亡的主要病原体之一。目前尚无能够提供针对DEC介导感染的广谱保护的许可疫苗。外膜囊泡(OMV)是革兰氏阴性细菌在生长阶段释放的微囊泡,含有多种免疫原性蛋白。基于感染的流行情况,我们制备了一种针对导致腹泻疾病的DEC五种主要致病型的五价外膜囊泡(POMV)免疫原。分离后,将来自五种DEC致病型的OMV等比例混合以制备POMV,并将10μg免疫原腹腔注射给成年BALB/c小鼠。三剂POMV诱导成年小鼠对从DEC致病型分离的全细胞裂解物(WCL)、外膜蛋白(OMP)和脂多糖(LPS)产生显著的体液免疫反应,并显著诱导细胞免疫反应。POMV免疫的成年小鼠血清的被动转移显著保护新生小鼠免受DEC感染。总体而言,本研究发现POMV在赋予新生小鼠针对五种主要DEC致病型的广谱被动保护方面具有免疫原性。总之,这些发现表明POMV可作为一种有效的疫苗候选物,以减轻DEC介导的健康负担。