The immunogenicity and protection effect of an inactivated coxsackievirus A6, A10, and A16 vaccine against hand,foot, and mouth disease

Coxsackievirus belongs to the Enterovirus genus of the Picornaviridae family and is one of the major pathogens associated with human hand, foot, and mouth disease (HFMD). Historically, outbreaks of HFMD have mainly been caused by enterovirus 71 and coxsackievirus A16. Recently, coxsackieviruses A6 and A10 have been associated with increased occurrences of sporadic HFMD cases and outbreak events globally. In this study, the immunogenicity of coxsackieviruses A6, A10, and A16 (CA6, CA10, and CA16), which were inactivated by formalin or β-propiolactone (BPL) under different conditions, was evaluated as multivalent vaccine candidates. CA6 induced similar immune responses with both inactivation methods, and the immune efficacy of CA10 and CA16 was better following inactivation with BPL than with formalin. There was no sufficient cross-reactivity or cross-protectivity against heterologous strains in groups vaccinated with the BPL-inactivated (BI) monovalent vaccine. Sufficient neutralizing antibody and cell-mediated immune responses were induced in the BI-trivalent vaccinated group. These findings suggest that BI-CA6, CA10, and CA16 are potential multivalent vaccine candidates and that a multivalent vaccine is needed to control HFMD. The coxsackievirus multivalent vaccine could be useful for the development of effective HFMD vaccines.     

上海市浦东新区食源性小肠结肠炎耶尔森菌耐药及分子流行病学特征

目的 了解上海市浦东新区食源性小肠结肠炎耶尔森菌耐药及分子流行病学特征。方法 2012-2016年主动、定点采集上海市浦东新区4类流通生鲜食品,使用冷增菌方法分离小肠结肠炎耶尔森菌,并分析菌株生物型、血清型、毒力基因型、耐药性和PFGE分子型别。结果 共采集食品3 900份（禽类590份、畜类1 074份、水产品1 488份、蔬菜748份）,其中111份（2.8%）检出小肠结肠炎耶尔森菌。禽类制品（5.3%,31/590）和畜类制品（4.5%,48/1 074）的检出率高于水产品（1.6%,24/1 488）和蔬菜制品（1.1%,8/748）。分离株以生物1A型（95.5%）和O：8血清型（42.3%）为主,且分离数与年总分离数呈正相关。所有菌株均缺失4种（ail、ystA、yadA和virF）产毒株标记的毒力基因,76株（68.5%）ystB基因阳性（其中35株属于1A/O：8/ystB）。分离株对氨苄西林（74.8%）和阿莫西林/克拉维酸（70.3%）的耐药率最高,对头孢西丁不敏感率超过50.0%;未发现三代头孢菌素或氟喹诺酮类抗菌药物耐药株,38.7%（43/111）的菌株为多重耐药。O：8和O：5血清型菌株分别存在44和18种PFGE分子型别。结论 上海市浦东新区食源性小肠结肠炎耶尔森菌暴露风险以禽类制品和畜类制品为主,优势菌型为1A/O：8/ystB,虽无典型产毒株特征但仍有潜在致病力。菌株耐药率处于较低水平但存在多重耐药株,PFGE分子型别提示菌株呈高度遗传多样性。