van Boxtel Renée A J, Verdijk Pauline, de Boer Otto J, van Riet Elly, Mensinga Tjeert T, Luytjes Willem
a Center for Infectious Diseases Control ; National Institute for Public Health and the Environment (RIVM) ; Bilthoven , The Netherlands.
Hum Vaccin Immunother. 2015;11(4):983-90. doi: 10.1080/21645515.2015.1012004.
Influenza vaccine production capacity is still insufficient to meet global demand in case of a pandemic. To expand worldwide influenza vaccine production capacity, a solid and transferable egg-based influenza vaccine production process was established that is suitable for upscaling and technology transfer to vaccine manufacturers in low- and middle-income countries. As a proof-of-concept, the safety and immunogenicity of a pandemic whole inactivated virus (WIV) vaccine (H5N1) and a monovalent seasonal WIV vaccine (H3N2) were evaluated in a phase I clinical trial in adults.
Subjects were vaccinated with 2 doses of pandemic WIV vaccine (pWIV), or one dose of either seasonal WIV vaccine (sWIV) or a commercially available trivalent comparator vaccine followed by a placebo dose. Haemagglutination inhibiting antibody titres against the influenza strains were determined before and 21 d after each vaccination.
The frequency and severity of adverse reactions were comparable between groups. No serious adverse events were reported. After a single dose of sWIV the seroconversion rate was 91% (Committee for Proprietary Medicinal Products (CPMP) criterion >40%), the seroprotection rate was 100% (CPMP criterion >70%), and the mean geometric mean titre (GMT) increase was 24.9 (CPMP criterion >2.5). After two doses of pWIV, seroconversion rate and seroprotection rate were both 71%, and the mean GMT increase was 7.8.
Both pWIV and sWIV were equally well-tolerated as the comparator vaccine, and both vaccines complied with all 3 CPMP criteria. EudraCT 2011-000159-17. Netherlands National Trial Register 2695.
在大流行情况下，流感疫苗的生产能力仍不足以满足全球需求。为扩大全球流感疫苗生产能力，建立了一种可靠且可转移的基于鸡蛋的流感疫苗生产工艺，该工艺适用于扩大规模并向低收入和中等收入国家的疫苗制造商进行技术转让。作为概念验证，在一项针对成年人的I期临床试验中评估了大流行全灭活病毒（WIV）疫苗（H5N1）和单价季节性WIV疫苗（H3N2）的安全性和免疫原性。
受试者接种2剂大流行WIV疫苗（pWIV），或1剂季节性WIV疫苗（sWIV）或市售三价对照疫苗，随后接种安慰剂。在每次接种前和接种后21天测定针对流感毒株的血凝抑制抗体滴度。
各组不良反应的频率和严重程度相当。未报告严重不良事件。单剂sWIV接种后，血清转化率为91%（欧洲药品评价局（CPMP）标准>40%），血清保护率为100%（CPMP标准>70%），平均几何平均滴度（GMT）增加24.9（CPMP标准>2.5）。两剂pWIV接种后，血清转化率和血清保护率均为71%，平均GMT增加7.8。
pWIV和sWIV与对照疫苗的耐受性相当，两种疫苗均符合所有3项CPMP标准。EudraCT 2011-000159-17。荷兰国家试验注册编号2695。
