Kuhlmann Frederick Matthew, Grigura Vadim, Vickers Timothy J, Prouty Michael G, Iannotti Lora L, Dulience Sherlie Jean Louis, Fleckenstein James M
Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine in Saint Louis, Saint Louis, MO 63110, USA.
U.S. Naval Medical Research Unit No. 6-NAMRU 6, Lima 15001, Peru.
Microorganisms. 2023 Aug 31;11(9):2221. doi: 10.3390/microorganisms11092221.
Enterotoxigenic Escherichia coli (ETEC) are common causes of infectious diarrhea among young children of low-and middle-income countries (LMICs) and travelers to these regions. Despite their significant contributions to the morbidity and mortality associated with childhood and traveler's diarrhea, no licensed vaccines are available. Current vaccine strategies may benefit from the inclusion of additional conserved antigens, which may contribute to broader coverage and enhanced efficacy, given their key roles in facilitating intestinal colonization and effective enterotoxin delivery. EatA and EtpA are widely conserved in diverse populations of ETEC, but their immunogenicity has only been studied in controlled human infection models and a population of children in Bangladesh. Here, we compared serologic responses to EatA, EtpA and heat-labile toxin in populations from endemic regions including Haitian children and subjects residing in Egypt, Cameroon, and Peru to US children and adults where ETEC infections are sporadic. We observed elevated IgG and IgA responses in individuals from endemic regions to each of the antigens studied. In a cohort of Haitian children, we observed increased immune responses following exposure to each of the profiled antigens. These findings reflect the wide distribution of ETEC infections across multiple endemic regions and support further evaluation of EatA and EtpA as candidate ETEC vaccine antigens.
产肠毒素大肠杆菌(ETEC)是低收入和中等收入国家(LMICs)幼儿以及前往这些地区的旅行者感染性腹泻的常见病因。尽管它们对儿童腹泻和旅行者腹泻的发病率和死亡率有重大影响,但目前尚无获得许可的疫苗。鉴于额外的保守抗原在促进肠道定植和有效输送肠毒素方面的关键作用,将其纳入当前疫苗策略可能有助于扩大覆盖范围并提高疗效。EatA和EtpA在不同的ETEC群体中广泛保守,但其免疫原性仅在受控人类感染模型和孟加拉国的一群儿童中进行过研究。在这里,我们比较了海地儿童以及居住在埃及、喀麦隆和秘鲁的受试者等流行地区人群与美国儿童和成人(ETEC感染为散发性)对EatA、EtpA和不耐热毒素的血清学反应。我们观察到流行地区个体对所研究的每种抗原的IgG和IgA反应均升高。在一组海地儿童中,我们观察到接触每种分析抗原后免疫反应增强。这些发现反映了ETEC感染在多个流行地区的广泛分布,并支持进一步评估EatA和EtpA作为候选ETEC疫苗抗原。