腸病毒71型疫苗研發

國際腸病毒71型疫苗研發進度 研發單位 國別 開發進度 病毒株 備註 國家衛生研究院 中華民國 完成Phase I B4 已技術移轉國光生技與基亞生技 國光生技 準備進行Phase II Phase II IND已有條件核准 基亞生技 已申請Phase II IND，待核准 中生集團 中國大陸 完成Phase Ⅲ C4 結果顯示該疫苗對由EV71型病毒引起的手足口病具有90%的保護率。(Lancet.2013 Jun 8 ;381(9882):2024-32.) 北京科興 初步結果顯示疫苗具有良好的安全性和有效性，對EV71型病毒導致的手足口病或疱疹性咽峽炎保護率為94.8% 。(N Engl J Med. 2014 Feb 27; 370(9):818-28.) 昆明生物所 結果顯示該疫苗對由EV71型病毒引起的手足口病具有97.4%的保護率。(N Engl J Med2014 Feb 27; 370(9):829-37.) Inviragen 新加坡 B 結果顯示該疫苗具安全性及免疫性 Sentinext 馬來西亞 Pre-clinical N/A bivalent VLP vaccine for EV71and CA16 2

(Inactivated vero cell-based alum-adjuvanted EV71 vaccine) 國家衛生研究院腸病毒71型疫苗研發 (Inactivated vero cell-based alum-adjuvanted EV71 vaccine) 疫苗生產所使用的細胞庫與病毒庫為符合國際標準並確定為安全且無遭受污染，因此委託英國專業檢驗公司(Bio-Reliance) 進行檢驗之確效作業，耗時近二年的時間證明其具安全且無致癌性。 自2007 年到2011 年間疫國衛院疫苗研發中心建立了符合國際規範PIC/S cGMP 生物製劑廠及發展細胞培養製程生產符合國際規範疫苗成品，促使腸病毒71 型疫苗進入第一期人體臨床試驗。 自2009 年開始生產腸病毒71 型疫苗後，於2010 年第一季向行政院衛生署食品藥物管理局(TFDA) 申請人體試驗。2010 年10 月份取得第一期人體臨床試驗許可證，同年12月份開始第一位受試者接種疫苗。

Phase I 臨床實驗設計 於2011年6月份完成第一階段10人臨床試驗，受試者的資料 由評估委員會判斷安全性良好，才進行第二階段50位受試者。2012年3月份完成所有受試者疫苗施打，並持續觀察受試者至2012年9月份。臨床試驗的資料顯示安全性良好，並引發顯著的中和能力。

Efficacy, safety, and immunology of an inactivated alum-adjuvant enterovirus 71 vaccine in children (Lancet.2013 Jun 8 ;381(9882):2024-32) Vaccine : Inactivated vero cell-based alum-adjuvanted EV71 vaccine ,containing 320 U of antigen and 0·18 mg of alum, was developed and manufactured by Beijing Vigoo Biological. Recipients : 10,245 Healthy infants and young children,6 to 35months of age, were vaccinated intramuscularly in the deltoid region on day0 and day28. Surveillance : The effect of EV71 vaccine was evaluated during a 12-month surveillance period.

Results : Vaccine effi cacy was 90·0% against EV71-associated HFMD disease and 80·4% against EV71-associated disease . Serious adverse events were reported by 62 of 5117 (1·2%) participants in the vaccine group versus 75 of 5123 (1·5%) in the placebo group. Conclusion : EV71 vaccine provides high efficacy, satisfactory safety, and sustained immunogenicity in infants and young children. .

Efficacy, Safety, and Immunogenicity of an Enterovirus 71 Vaccine in China(N Engl. J. Med 2014;370 : 818-828.) Vaccine : The Vero cell-based inactivated human EV71 vaccine(Sinovac Biotech) contained 400U of EV71 antigen with alum adjuvant was packaged in syringes (0.5ml per vial). Recipients : 10,077 Healthy infants and young children,6 to 35months of age, were vaccinated intramuscularly in the deltoid region on day0 and day28. Surveillance : The effect of EV71 vaccine was evaluated during a 12-month surveillance period from day 57 to month 14.

Results : The vaccine efficacy against EV-71 associated HFM disease was 94.8%. The vaccine efficacy against EV-71 associated hospitalization and neurologic complications were both 100%. Conclusion : The EV-71 vaccine provided protection against EV-71 associated HFM disease in infants and young children. 2. Future Vaccine manufacturer Sinovac has been awarded a US$9.6 million grant for the construction of a hand, foot and mouth disease vaccine facility. Sinovac filed a new drug application (NDA) for its proprietary EV71 vaccine. The NDA is currently under review by Centers for Drug Evaluation.

An Inactivated Enterovirus 71 Vaccine in Healthy Children(N Engl. J An Inactivated Enterovirus 71 Vaccine in Healthy Children(N Engl. J. Med 2014;370 : 829-837.) Vaccine : The diploid-cell line (KMB17 strain) inactivated vaccine contained 100 U of inactivated EV71 viral antigen adsorbed to 0.5 mg of aluminum hydroxide and suspended in 0.5 ml of buffered saline. Recipients : 12,000 Healthy infants and young children,6 to 72months of age, were vaccinated intramuscularly in the deltoid region on day0 and day28. Surveillance : The effect of EV71 vaccine was evaluated during a 11-month surveillance period.

Results : The seroconversion rate was 100% 4 weeks after the two vaccinations, with a geometric mean titer of 170.6. Over the course of two epidemic seasons, the vaccine efficacy was 97.4%. Conclusion : The inactivated EV71 vaccine elicited EV71-specific immune responses and protection against EV71-associated hand, foot, and mouth disease.