Knuf Markus, Leroux-Roels Geert, Rümke Hans C, Abarca Katia, Rivera Luis, Lattanzi Maria, Pedotti Paola, Arora Ashwani, Kieninger-Baum Dorothee, Della Cioppa Giovanni
Zentrum für Kinder-und Jugendmedizin, Universitätsmedizin, Mainz, Germany.
Center for Vaccinology, Ghent University and Hospital, Ghent, Belgium.
Vaccine. 2015 Jan 1;33(1):174-81. doi: 10.1016/j.vaccine.2014.10.085. Epub 2014 Nov 11.
This study was designed to identify the optimal dose of an MF59-adjuvanted, monovalent, A/H1N1 influenza vaccine in healthy paediatric subjects.
Subjects aged 3-8 years (n=194) and 9-17 years (n=160) were randomized to receive two primary doses of A/H1N1 vaccine containing either 3.75 μg antigen with half a standard dose of MF59 adjuvant, 7.5 μg antigen with a full dose of MF59, or (children 3-8 years only), a non-adjuvanted 15 μg formulation. A booster dose of MF59-adjuvanted seasonal influenza vaccine including homologous A/H1N1 strain was given one year after priming. Immunogenicity was assessed by haemagglutination inhibition (HI) and microneutralization assays. Vaccine safety was assessed throughout the study (up to 18 months).
A single priming dose of either MF59-adjuvanted formulation was sufficient to meet the European licensure criteria for pandemic influenza vaccines (HI titres ≥1:40>70%; seroconversion>40%; and GMR>2.5). Two non-adjuvanted vaccine doses were required to meet the same licensure criteria. After first and second doses, percentage of subjects with HI titres ≥1:40 were between 97% and 100% in the adjuvanted vaccine groups compared with 68% and 91% in the non-adjuvanted group, respectively. Postvaccination seroconversion rates ranged from 91% to 98% in adjuvanted groups and were 68% (first dose) and 98% (second dose) in the non-adjuvanted group. HI titres ≥1:330 after primary doses were achieved in 69% to 90% in adjuvanted groups compared with 41% in the non-adjuvanted group. Long-term antibody persistence after priming and a robust antibody response to booster immunization were observed in all vaccination groups. All A/H1N1 vaccine formulations were generally well tolerated. No vaccine-related serious adverse events occurred, and no subjects were withdrawn from the study due to an adverse event.
An MF59-adjuvanted influenza vaccine containing 3.75 μg of A/H1N1 antigen was well tolerated and sufficiently immunogenic to meet all the European licensure criteria after a single dose in healthy children 3-17 years old.
本研究旨在确定MF59佐剂单价A/H1N1流感疫苗在健康儿童受试者中的最佳剂量。
将3至8岁（n = 194）和9至17岁（n = 160）的受试者随机分组，接受两剂含3.75μg抗原及半剂标准剂量MF59佐剂、7.5μg抗原及一剂全量MF59佐剂的A/H1N1疫苗，或（仅3至8岁儿童）一剂15μg无佐剂疫苗。在初次接种一年后给予一剂含同源A/H1N1毒株的MF59佐剂季节性流感疫苗加强针。通过血凝抑制（HI）和微量中和试验评估免疫原性。在整个研究期间（长达18个月）评估疫苗安全性。
任何一种MF59佐剂疫苗的单次初免剂量均足以满足欧洲大流行性流感疫苗的许可标准（HI效价≥1:40>70%；血清阳转率>40%；几何平均倍数（GMR）>2.5）。无佐剂疫苗需要两剂才能达到相同的许可标准。在初次和第二次接种后，佐剂疫苗组中HI效价≥1:40的受试者百分比分别为97%至100%，而无佐剂组分别为68%和91%。接种疫苗后的血清阳转率在佐剂组中为91%至98%，在无佐剂组中分别为68%（第一剂）和98%（第二剂）。初次接种后HI效价≥1:330的受试者在佐剂组中为69%至90%，而无佐剂组为41%。在所有疫苗接种组中均观察到初次接种后抗体的长期持久性以及对加强免疫的强烈抗体反应。所有A/H1N1疫苗制剂总体耐受性良好。未发生与疫苗相关的严重不良事件，也没有受试者因不良事件退出研究。
含3.75μg A/H1N1抗原的MF59佐剂流感疫苗耐受性良好，免疫原性足以使3至17岁健康儿童在单次接种后满足所有欧洲许可标准。
