Department of Immunology and Medicine, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.
PLoS One. 2013;8(3):e59674. doi: 10.1371/journal.pone.0059674. Epub 2013 Mar 26.
Recent studies have demonstrated that inactivated seasonal influenza vaccines (IIV) may elicit production of heterosubtypic antibodies, which can neutralize avian H5N1 virus in a small proportion of subjects. We hypothesized that prime boost regimens of live and inactivated trivalent seasonal influenza vaccines (LAIV and IIV) would enhance production of heterosubtypic immunity and provide evidence of cross-protection against other influenza viruses.
In an open-label study, 26 adult volunteers were randomized to receive one of four vaccine regimens containing two doses of 2009-10 seasonal influenza vaccines administered 8 (±1) weeks apart: 2 doses of LAIV; 2 doses of IIV; LAIV then IIV; IIV then LAIV. Humoral immunity assays for avian H5N1, 2009 pandemic H1N1 (pH1N1), and seasonal vaccine strains were performed on blood collected pre-vaccine and 2 and 4 weeks later. The percentage of cytokine-producing T-cells was compared with baseline 14 days after each dose.
Subjects receiving IIV had prompt serological responses to vaccine strains. Two subjects receiving heterologous prime boost regimens had enhanced haemagglutination inhibition (HI) and neutralization (NT) titres against pH1N1, and one subject against avian H5N1; all three had pre-existing cross-reactive antibodies detected at baseline. Significantly elevated titres to H5N1 and pH1N1 by neuraminidase inhibition (NI) assay were observed following LAIV-IIV administration. Both vaccines elicited cross-reactive CD4+ T-cell responses to nucleoprotein of avian H5N1 and pH1N1. All regimens were safe and well tolerated.
Neither homologous nor heterologous prime boost immunization enhanced serum HI and NT titres to 2009 pH1N1 or avian H5N1 compared to single dose vaccine. However heterologous prime-boost vaccination did lead to in vitro evidence of cross-reactivity by NI; the significance of this finding is unclear. These data support the strategy of administering single dose trivalent seasonal influenza vaccine at the outset of an influenza pandemic while a specific vaccine is being developed.
ClinicalTrials.gov NCT01044095.
最近的研究表明，灭活季节性流感疫苗（IIV）可能会引发异源抗体的产生，而这些抗体可以中和一小部分人群中的禽流感 H5N1 病毒。我们假设，使用活疫苗和灭活三价季节性流感疫苗（LAIV 和 IIV）进行初次加强免疫接种方案会增强异源免疫的产生，并提供对其他流感病毒的交叉保护证据。
在一项开放性标签研究中，26 名成年志愿者被随机分配接受四种疫苗方案中的一种，每种方案均包含两剂 2009-10 季节性流感疫苗，间隔 8（±1）周：LAIV 两剂；IIV 两剂；LAIV 后 IIV；IIV 后 LAIV。在接种疫苗前和接种后 2 周和 4 周采集血液，进行针对禽流感 H5N1、2009 年大流行 H1N1（pH1N1）和季节性疫苗株的体液免疫测定。在每次接种后 14 天，与基线相比，比较细胞因子产生 T 细胞的百分比。
接受 IIV 的受试者对疫苗株有快速的血清学反应。两名接受异源初次加强免疫接种方案的受试者对 pH1N1 和禽流感 H5N1 的血凝抑制（HI）和中和（NT）滴度增强，其中一名受试者对禽流感 H5N1 也有增强；所有三名受试者在基线时都检测到预先存在的交叉反应性抗体。在接受 LAIV-IIV 给药后，通过神经氨酸酶抑制（NI）测定观察到对 H5N1 和 pH1N1 的显著升高的滴度。两种疫苗都引发了针对禽流感 H5N1 和 pH1N1 的核蛋白的交叉反应性 CD4+T 细胞反应。所有方案均安全且耐受良好。
与单剂量疫苗相比，同源或异源初次加强免疫接种均未增强血清 HI 和 NT 对 2009 年 pH1N1 或禽流感 H5N1 的滴度。然而，异源初次加强接种确实导致了通过 NI 的体外交叉反应性证据；这一发现的意义尚不清楚。这些数据支持在流感大流行开始时，同时正在开发特定疫苗的情况下，采用单剂量三价季节性流感疫苗的策略。
ClinicalTrials.gov NCT01044095。
