国产四价流感病毒裂解疫苗在婴幼儿接种中的安全性及免疫原性初探

Preliminary evaluation on safety and immunogenicity of a China-made split-virion quadrivalent influenza vaccine in infants

目的初步评价国产四价流感病毒裂解疫苗在婴幼儿接种中的安全性和免疫原性。方法采用单中心、剂量递增、开放设计,受试者为6~35月龄健康婴幼儿,按0、28 d接种低或高剂量试验疫苗。收集安全性数据,随访首剂接种至全程接种后半年内严重不良事件。采集首剂接种前和每剂接种后第28 d静脉血,检测H1N1、H3N2、BV(B/Victoria)、BY(B/Yamagata)型流感病毒血凝抑制抗体。结果本研究低、高剂量组各入组30人,接种后7 d内不良反应发生率为21.7%,28 d不良事件发生率为26.7%,低、高剂量组2个时段不良反应发生率差异均无统计学意义(P值均>0.05)。不良反应发生多为1级或2级,研究期间发生3例严重不良事件,均与试验疫苗无关。全程免疫后第28 d,各型抗体阳转率在30.8%~48.1%,保护率在46.2%~61.5%,各型抗体几何平均滴度(GMT)在25.9~75.8,几何平均增长倍数(GMI)在3.06~5.17;免前阴性人群低、高剂量组H3N2型抗体GMT(1∶13.2 vs.1∶31.7)和GMI(2.64 vs.6.35),组间差异均有统计学意义(P值均<0.05),其他人群2种剂量组各型抗体阳转率、保护率、GMT、GMI差异均无统计学意义(P值均>0.05)。结论6~35月龄婴幼儿可耐受该四价流感病毒裂解疫苗,具有较好的安全性;高剂量疫苗在免疫原性方面略优于低剂量疫苗。

Objective To preliminarily evaluate the safety and immunogenicity of a China-made split-virion quadrivalent influenza vaccine in infants.Methods A single-center,dose-escalating,open-label trial was performed in healthy infants aged 6-35 months.Subjects received 2 doses of low-dose or high-dose experimental vaccine according to the 0 and 28-d immunization schedule.Diary cards were used to collect safety data,and serious adverse events(SAE)were followed up from the first dose to half a year after full vaccination.Venous blood samples were collected before the first dose and on the 28 th day after each dose of inoculation and hemagglutination inhibitory(HI)antibodies of H1 N1,H3 N2,BV(B/Victoria)and BY(B/Yamagata)influenza viruses were detected.Results In this trial,30 participants were enrolled in each dose group.In general,the incidence of adverse reactions within 7 d and 28 d were 21.7%and 26.7%,respectively;there was no significant difference in the incidence of adverse reactions between the low and high dose groups in the 2 time periods(all P>0.05).Most of adverse events were grade 1 or 2,totally 3 SAEs occurred during the study period,none were related to the experimental vaccine.On 28 d after full immunization,the positive conversion rates various types of antibodies were from 30.8%to 48.1%,and protection rates were from 46.2%to 61.5%,the geometric mean titer(GMT)of various types of antibodies were from 25.9 to 75.8,the geometric mean increase(GMI)were from 3.06 to 5.17.Only in the pre-immunization negative group,the GMT(1:13.2 vs.1:31.7)and GMI(2.64 vs.6.35)of H3 N2 antibody in the low and high dose groups were statistically significant(all P<0.05),while the positive conversion rates,protection rates,GMT and GMI of the 2 dose groups in other populations were not statistically significant(all P>0.05).Conclusion The test vaccine can be tolerated among infants aged 6-35 months and has good safety;high-dose inoculation is slightly better than low-dose inoculation in terms of immunogenicity.