Fast rise of broadly cross-reactive antibodies after boosting long-lived human memory B cells primed by an MF59 adjuvanted prepandemic vaccine
Fast rise of broadly cross-reactive antibodies after boosting long-lived human memory B cells primed by an MF59 adjuvanted prepandemic vaccine
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DOI：
10.1073/pnas.0903181106
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发表时间：
2009-05-12
影响因子：
11.1
通讯作者：
Stephenson, Iain
中科院分区：
文献类型：
--
作者：
Galli, Grazia;Hancock, Kathy;Stephenson, Iain
在下一次流感大流行之前的主动引发可以诱导对新流感抗原的免疫记忆应答。在一项开放标签研究中，我们分析了54名成年人的B细胞记忆和抗体应答，这些成年人接受了2剂7.5 μ g剂量的MF 59佐剂A/Vietnam/1194/2004进化枝1（H5 N1）疫苗。在1999-2001年期间，24名受试者先前用MF 59佐剂或普通进化枝0样A/鸭/新加坡/1997（H5 N3）疫苗初免。在致敏和未致敏个体中，对A/Vietnam/1194/2004反应的循环记忆B细胞的接种前频率均较低。然而，在加强后第21天，MF 59佐剂致敏的受试者比普通致敏或未致敏的受试者显示出更高频率的H5 N1特异性记忆B细胞。免疫记忆通过单次疫苗施用被迅速动员，并且在第7天已经导致针对抗原性多样的进化枝0、1和2的中和抗体的高滴度。一般来说，接种疫苗后抗体滴度显着高于在未引发的主题。与普通疫苗相比，用MF 59佐剂疫苗引发的受试者的反应明显更好，最明显的是在交叉反应抗体应答的早期诱导和持续时间方面。6个月后，在MF 59致敏的受试者中仍可检测到高滴度的交叉反应性抗体。我们的结论是，与进化枝0-样H5 N3的远距离引发诱导了交叉反应性记忆B细胞的池，这些细胞可以在多年后通过错配的MF 59佐剂疫苗快速增强，以快速产生高滴度的交叉反应性中和抗体。这些结果表明，应考虑大流行前的疫苗接种策略。
Proactive priming before the next pandemic could induce immune memory responses to novel influenza antigens. In an open-label study, we analyzed B cell memory and antibody responses of 54 adults who received 2 7.5-mu g doses of MF59-adjuvanted A/Vietnam/1194/2004 clade 1 (H5N1) vaccine. Twenty-four subjects had been previously primed with MF59-adjuvanted or plain clade 0-like A/duck/Singapore/1997 (H5N3) vaccine during 1999-2001. The prevaccination frequency of circulating memory B cells reactive to A/Vietnam/1194/2004 was low in both primed and unprimed individuals. However, at day 21 after boosting, MF59-adjuvanted primed subjects displayed a higher frequency of H5N1-specific memory B cells than plain-primed or unprimed subjects. The immune memory was rapidly mobilized by a single vaccine administration and resulted in high titers of neutralizing antibodies to antigenically diverse clade 0, 1, and 2 H5N1 viruses already at day 7. In general, postvaccination antibody titers were significantly higher in primed subjects than in unprimed subjects. Subjects primed with MF59-adjuvanted vaccine responded significantly better than those primed with plain vaccine, most notably in early induction and duration of cross-reacting antibody responses. After 6 months, high titers of cross-reactive antibody remained detectable among MF59-primed subjects. We conclude that distant priming with clade 0-like H5N3 induces a pool of cross-reactive memory B cells that can be boosted rapidly years afterward by a mismatched MF59-adjuvanted vaccine to generate high titers of cross-reactive neutralizing antibodies rapidly. These results suggest that pre-pandemic vaccination strategies should be considered.