Biomedical Advanced Research and Development Authority (BARDA), Office of the Assistant Secretary for Preparedness and Response (ASPR), Department of Health and Human Services (HHS), Washington, DC, USA.
St. Jude Children's Research Hospital, Memphis, TN, USA.
Vaccine. 2019 Jan 14;37(3):435-443. doi: 10.1016/j.vaccine.2018.11.069. Epub 2018 Dec 12.
As part of the U.S. Department of Health and Human Services (HHS) Pandemic Influenza Plan preparedness and response strategy, the National Pre-Pandemic Influenza Vaccine Stockpile (NPIVS) program was established by the Biomedical Advanced Research and Development Authority (BARDA) in 2005 with the goal of building and maintaining a stockpile of vaccines for influenza viruses with pandemic potential to vaccinate 20 million people in the critical workforce in the event of a pandemic. The NPIVS program continuously monitors the integrity of influenza vaccine antigens and adjuvants stored within the stockpile. In addition to monitoring physical and chemical properties in stability studies, it is important to regularly assess the safety and immunogenicity of stockpiled vaccines and adjuvants to maintain preparedness for use in the event of an influenza pandemic.
BARDA conducted a randomized, double-blinded Phase 2 clinical study with the oldest stockpiled influenza A(H5N1) antigen, stored over the previous 10-12 years administered with or without MF59® adjuvant, stored over the previous 2-7 years at the time of vaccination.
Stockpiled vaccines were well-tolerated, adverse events were generally mild, and there was no drop in immunogenicity to the oldest stockpiled A(H5N1) vaccine. Compared to unadjuvanted vaccine, greater peak antibody responses were observed in subjects who were vaccinated with MF59-adjuvanted vaccines, regardless of antigen dose. Vaccination with the A(H5N1) vaccine antigen also results in cross-reactive antibody responses to contemporary circulating strains of A(H5) influenza viruses.
The frequency, type, and severity of AEs observed during this study are similar to historical clinical study data with A(H5N1) vaccines and MF59 adjuvant indicating that a stockpiled A(H5N1) vaccine appears to remain safe and tolerable. The vaccines were immunogenic when administered as a two-dose vaccine regimen in healthy adults, despite extended storage of HA antigen or MF59 adjuvant within the NPIVS.
ClinicalTrials.gov: NCT02680002.
作为美国卫生与公众服务部（HHS）大流行性流感计划防备和应对战略的一部分，生物医学高级研究与发展管理局（BARDA）于 2005 年建立了国家大流行性流感预备疫苗储备（NPIVS）计划，目标是为具有大流行潜力的流感病毒建立和维持储备疫苗，以便在大流行时为 2000 万关键劳动力人群进行疫苗接种。NPIVS 计划持续监测储备疫苗中的流感疫苗抗原和佐剂的完整性。除了在稳定性研究中监测物理和化学特性外，定期评估储备疫苗和佐剂的安全性和免疫原性对于在流感大流行时做好使用准备非常重要。
BARDA 进行了一项随机、双盲、2 期临床试验，使用最古老的储备 A(H5N1) 抗原（储存超过 10-12 年），或与储存超过 2-7 年的 MF59®佐剂联合使用，对疫苗进行接种。
储备疫苗具有良好的耐受性，一般不良事件轻微，且对最古老的储备 A(H5N1)疫苗的免疫原性没有下降。与未加佐剂的疫苗相比，接受 MF59 佐剂疫苗接种的受试者观察到更高的峰值抗体反应，无论抗原剂量如何。接种 A(H5N1)疫苗抗原还会导致对当代流行的 A(H5)流感病毒株产生交叉反应性抗体反应。
在这项研究中观察到的 AE 频率、类型和严重程度与 A(H5N1)疫苗和 MF59 佐剂的历史临床研究数据相似，表明储备的 A(H5N1)疫苗似乎仍然安全且耐受。尽管 NPIVS 中 HA 抗原或 MF59 佐剂的储存时间延长，但储备疫苗在健康成年人中作为两剂疫苗方案接种时仍具有免疫原性。
ClinicalTrials.gov：NCT02680002。
