Prior Population Immunity Reduces the Expected Impact of CTL-Inducing Vaccines for Pandemic Influenza Control
Prior Population Immunity Reduces the Expected Impact of CTL-Inducing Vaccines for Pandemic Influenza Control
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DOI：
10.1371/journal.pone.0120138
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发表时间：
2015-03-26
期刊：
影响因子：
3.7
通讯作者：
McVernon, Jodie
中科院分区：
文献类型：
--
作者：
Bolton, Kirsty J.;McCaw, James M.;McVernon, Jodie
引发流感特异性细胞毒性T细胞（CTL）反应的疫苗可能通过限制新型甲型流感病毒（IAV）的传播来帮助控制大流行。我们考虑在一系列流行病学上合理的大流行情景中使用假设的ctl诱导疫苗进行干预。我们估计了可实现的发病率降低，并通过采用将流行病进展与IAV变体的出现联系起来的模型，估计了抗原漂移的机会。我们证明，如果在成人中广泛发现的流感特异性T细胞已经抑制了传播并且证明难以增强，那么ctl诱导疫苗在改变人群水平结果方面的效用有限。在“经历过流感”和“未经历流感”的宿主中施用有效的ctl诱导疫苗，可能会充分减缓传播，从而减轻中度IAV大流行。然而，如果针对新出现的IAV的中和性交叉反应抗体在经历过流感的宿主中很常见，就像猪变种H3N2v一样，增强CTL免疫可能对减少群体传播无效，这表明CTL诱导疫苗最好用于对抗H7N9等新型亚型。除非疫苗不能轻易地抑制来自具有初始T细胞池的受感染宿主的传播，否则靶向流感初始宿主是可取的。如果幼稚的宿主通常是密集混合的儿童，并且当一部分有经验的宿主预先存在中和交叉反应抗体时，这种策略的益处会增强。我们发现ctl诱导的疫苗接种运动可能比以前认为的具有更大的抑制抗原漂移的能力，当疫苗接种运动没有能力降低发病率时，针对成年人可能是实现这一目标的最佳策略。我们的研究结果强调了基于预先存在的细胞免疫和对疫苗效力的宿主决定因素的了解设计干预措施的必要性，并为评估高影响ctl诱导疫苗的性能要求提供了一个框架。
Vaccines that trigger an influenza-specific cytotoxic T cell (CTL) response may aid pandemic control by limiting the transmission of novel influenza A viruses (IAV). We consider interventions with hypothetical CTL-inducing vaccines in a range of epidemiologically plausible pandemic scenarios. We estimate the achievable reduction in the attack rate, and, by adopting a model linking epidemic progression to the emergence of IAV variants, the opportunity for antigenic drift. We demonstrate that CTL-inducing vaccines have limited utility for modifying population-level outcomes if influenza-specific T cells found widely in adults already suppress transmission and prove difficult to enhance. Administration of CTL-inducing vaccines that are efficacious in "influenza-experienced" and "influenza-naive" hosts can likely slow transmission sufficiently to mitigate a moderate IAV pandemic. However if neutralising cross-reactive antibody to an emerging IAV are common in influenza-experienced hosts, as for the swine-variant H3N2v, boosting CTL immunity may be ineffective at reducing population spread, indicating that CTL-inducing vaccines are best used against novel subtypes such as H7N9. Unless vaccines cannot readily suppress transmission from infected hosts with naive T cell pools, targeting influenza-naive hosts is preferable. Such strategies are of enhanced benefit if naive hosts are typically intensively mixing children and when a subset of experienced hosts have pre-existing neutralising cross-reactive antibody. We show that CTL-inducing vaccination campaigns may have greater power to suppress antigenic drift than previously suggested, and targeting adults may be the optimal strategy to achieve this when the vaccination campaign does not have the power to curtail the attack rate. Our results highlight the need to design interventions based on pre-existing cellular immunity and knowledge of the host determinants of vaccine efficacy, and provide a framework for assessing the performance requirements of high-impact CTL-inducing vaccines.