手足口病產生於20世紀中期,已成為一種廣泛流行於嬰幼兒的傳染性疾病。臨床症狀主要為發熱以及手、足、口腔等部位的皰疹,少數患兒可引起心肌炎、肺水腫、無菌性腦膜腦炎等併發症而導致死亡。近幾年,疫情在全世界許多國家和地區先後爆發,已成為重大的公共衛生隱患,引起社會的廣泛關注。開發手足口病預防性疫苗也成為疫苗研究領域的一個重點。
手足口病是由腸道病毒引起的傳染病。臨床診斷和流行病調查結果顯示,我國的手足口病主要由腸道病毒71型(EV71)和柯薩奇病毒A16型(CA16)的感染引起。因此,開發能夠同時預防EV71和CA16感染的雙價疫苗是防控手足口病的重要手段。
中國科學院上海巴斯德研究所蔡一村博士在研究員黃忠的指導下,開展了抗EV71和CA16雙價疫苗的研發工作。研究人員製備了基於滅活病毒的單價EV71疫苗、單價CA16疫苗和包含以上兩種抗原的雙價疫苗,並在小鼠模型上評價單、雙價疫苗的免疫原性和抗病毒效果。結果顯示,單價疫苗所誘導產生的抗體只能夠抵抗同型病毒的體外和體內感染,而對於異型病毒沒有保護效果;雙價疫苗免疫小鼠血清在體外可以有效中和EV71和CA16兩種病毒,並且保護小鼠免於致死劑量的EV71或CA16病毒攻擊。研究表明,實驗性雙價疫苗中的EV71和CA16抗原間不存在免疫競爭和拮抗,能夠在動物體內平衡地誘發針對EV71和CA16的有效免疫保護反應。
相關研究結果在線發表於國際學術刊物Vaccine(A combination vaccine comprising of inactivated enterovirus 71 and coxsackievirus A16 elicits balanced protective immunity against both viruses)。
此項研究獲得國家自然科學基金、中科院知識創新工程、上海市生物醫藥領域科技支撐計劃和巴斯德健康研究基金會的經費支持。(生物谷Bioon.com)
生物谷推薦的英文摘要:
Vaccine doi:10.1016/j.vaccine.2014.03.012
A combination vaccine comprising of inactivated enterovirus 71 and coxsackievirus A16 elicits balanced protective immunity against both viruses.
Cai Y1, Ku Z1, Liu Q1, Leng Q1, Huang Z2.
Enterovirus 71 (EV71) and coxsackievirus A16 (CA16) are the two major causative agents of hand, foot and mouth disease (HFMD), which is an infectious disease frequently occurring in children. A bivalent vaccine against both EV71 and CA16 is highly desirable. In the present study, we compare monovalent inactivated EV71, monovalent inactivated CA16, and a combination vaccine candidate comprising of both inactivated EV71 and CA16, for their immunogenicity and in vivo protective efficacy. The two monovalent vaccines were found to elicit serum antibodies that potently neutralized the homologous virus but had no or weak neutralization activity against the heterologous one; in contrast, the bivalent vaccine immunized sera efficiently neutralized both EV71 and CA16. More importantly, passive immunization with the bivalent vaccine protected mice against either EV71 or CA16 lethal infections, whereas the monovalent vaccines only prevented the homologous but not the heterologous challenges. Together, our results demonstrate that the experimental bivalent vaccine comprising of inactivated EV71 and CA16 induces a balanced protective immunity against both EV71 and CA16, and thus provide proof-of-concept for further development of multivalent vaccines for broad protection against HFMD.