Dept. of Health Sciences, University of Genoa, Italy.
Vaccine. 2012 Apr 16;30(18):2908-13. doi: 10.1016/j.vaccine.2012.02.003. Epub 2012 Feb 15.
The aim of the present study was to explore the ability of Intanza(®) 15 μg, the intradermal (ID) trivalent inactivated split-virion influenza vaccine containing 15 μg hemagglutinin per strain, to enhance the antibody responses against heterologous circulating H3N2 strains in adults 60 years and older. During the 2006-2007 influenza season, subjects aged 60 years or older were randomly assigned to receive one dose of ID or an intramuscular (IM, Vaxigrip(®)) influenza vaccine, which contained the reassortant A/Wisconsin/67/05(H3N2) strain as the H3N2 component. Antibody responses were assessed against the homologous vaccine strain, against the A/Brisbane/10/07(H3N2) reassortant strain and against four heterologous H3N2 field isolates (A/Genoa/62/05(H3N2), A/Genoa/3/07(H3N2), A/Genoa/2/07(H3N2), A/Genoa/3/06(H3N2)). The viruses tested belonged to three different clades that were closely related antigenically to A/California/7/04(H3N2), A/Nepal/921/06(H3N2) and A/Brisbane/10/07(H3N2). Antibody responses to these viruses were measured in 25 subjects per group using both haemagglutination inhibition (HI) and neutralization (NT) assays. At least one Committee for Medicinal Products for Human Use (CHMP) immunogenicity criteria for vaccine approval in the elderly was reached by both vaccines against all the viruses used in the study. All three CHMP criteria were reached against A/California/7/04(H3N2)-like, A/Nepal/921/06(H3N2)-like and A/Brisbane/10/07(H3N2)-like viruses by Intanza(®) 15 μg ID vaccine, while IM vaccination did not meet seroprotection criteria against circulating A/Nepal/921/06(H3N2)-like and A/Brisbane/10/07(H3N2)-like viruses or seroconversion criteria against A/Brisbane/10/07(H3N2)-like viruses. Post-vaccination HI titer, seroconversion, and seroprotection rates were higher against all viruses in subjects who received Intanza(®) 15 μg. The superiority of the seroprotection rate against the A/Nepal/921/06(H3N2)-like strain attained statistical significance despite the small sample size. Upon Beyer correction for pre-vaccination status, post-immunization HI titers against A/California/7/04(H3N2)-like and A/Brisbane/10/07(H3N2)-like strains and NT post-immunization titers against A/Wisconsin/67/05(H3N2), A/California/7/04(H3N2)-like, A/Brisbane/10/07(H3N2)-like strains were significantly higher in subjects immunized with Intanza(®) 15 μg than in individuals receiving IM vaccine. This study, although limited in the size of study population, demonstrated the broader immune response elicited by an ID influenza vaccine vs. a standard IM influenza vaccine against heterologous viruses including field isolates.
本研究旨在探索 Intanza(®)15μg （含 15μg 血凝素的三价流感疫苗）在 60 岁及以上成人中增强针对异源流行 H3N2 株的抗体应答的能力。在 2006-2007 年流感季节，60 岁及以上的受试者被随机分配接受一剂 ID 或肌肉内（IM，Vaxigrip(®)）流感疫苗，其中含有重配 A/Wisconsin/67/05(H3N2)株作为 H3N2 成分。针对同源疫苗株、A/Brisbane/10/07(H3N2)重配株和四种异源 H3N2 野毒株（A/Genoa/62/05(H3N2)、A/Genoa/3/07(H3N2)、A/Genoa/2/07(H3N2)、A/Genoa/3/06(H3N2)）评估了抗体应答。所测试的病毒属于与 A/California/7/04(H3N2)、A/Nepal/921/06(H3N2)和 A/Brisbane/10/07(H3N2)密切相关的三个不同的分支，具有抗原性。在每组 25 名受试者中使用血凝抑制（HI）和中和（NT）测定法测量了针对这些病毒的抗体应答。两种疫苗均至少达到了老年人人用药品委员会（CHMP）对疫苗批准的一项免疫原性标准，针对研究中使用的所有病毒。Intanza(®)15μg ID 疫苗针对 A/California/7/04(H3N2)-样、A/Nepal/921/06(H3N2)-样和 A/Brisbane/10/07(H3N2)-样病毒达到了所有三个 CHMP 标准，而 IM 疫苗针对流行的 A/Nepal/921/06(H3N2)-样和 A/Brisbane/10/07(H3N2)-样病毒未达到血清保护标准，针对 A/Brisbane/10/07(H3N2)-样病毒也未达到血清转化标准。接受 Intanza(®)15μg 的受试者针对所有病毒的接种后 HI 滴度、血清转化率和血清保护率均较高。尽管样本量较小，但针对 A/Nepal/921/06(H3N2)-样株的血清保护率优势达到了统计学意义。在 Beyer 校正接种前状态后，Intanza(®)15μg 免疫后针对 A/California/7/04(H3N2)-样和 A/Brisbane/10/07(H3N2)-样株的 HI 滴度和针对 A/Wisconsin/67/05(H3N2)、A/California/7/04(H3N2)-样、A/Brisbane/10/07(H3N2)-样株的 NT 接种后滴度均显著高于接受 IM 疫苗的受试者。尽管研究人群规模有限，但这项研究表明，与标准 IM 流感疫苗相比，ID 流感疫苗在针对包括野毒株在内的异源病毒时可引发更广泛的免疫应答。
