Abstract：
Influenza A has two hemagglutinin groups, with stronger cross-immunity to reinfection within than between groups. Here, we explore the implications of this heterogeneity for proposed cross-protective influenza vaccines that may offer broad, but not universal, protection. While the development goal for the breadth of human influenza A vaccine is to provide cross-group protection, vaccines in current development stages may provide better protection against target groups than non-target groups. To evaluate vaccine formulation and strategies, we propose a novel perspective: a vaccine population-level target product profile (PTPP). Under this perspective, we use dynamical models to quantify the epidemiological impacts of future influenza A vaccines as a function of their properties. Our results show that the interplay of natural and vaccine-induced immunity could strongly affect seasonal subtype dynamics. A broadly protective bivalent vaccine could lower the incidence of both groups and achieve elimination with sufficient vaccination coverage. However, a univalent vaccine at low vaccination rates could permit a resurgence of the non-target group when the vaccine provides weaker immunity than natural infection. Moreover, as a proxy for pandemic simulation, we analyze the invasion of a variant that evades natural immunity. We find that a future vaccine providing sufficiently broad and long-lived cross-group protection at a sufficiently high vaccination rate, could prevent pandemic emergence and lower the pandemic burden. This study highlights that as well as effectiveness, breadth and duration should be considered in epidemiologically informed TPPs for future human influenza A vaccines.
摘要：
甲型流感有两个血凝素组，与群体之间相比，内部对再感染的交叉免疫力更强。这里,我们探讨了这种异质性对拟议的交叉保护性流感疫苗的影响，这些疫苗可能提供广泛的，但不是普遍的，保护。虽然人类甲型流感疫苗的开发目标是提供跨群体保护，目前发展阶段的疫苗可能比非目标群体对目标群体提供更好的保护。为了评估疫苗配方和策略，我们提出了一个新的观点：疫苗群体水平目标产品概况(PTPP)。在这个视角下,我们使用动态模型来量化未来甲型流感疫苗的流行病学影响,作为其特性的函数.我们的结果表明，天然免疫和疫苗诱导免疫的相互作用可以强烈影响季节性亚型动态。广泛保护性的二价疫苗可以降低两组的发病率，并以足够的疫苗接种覆盖率实现消除。然而,低疫苗接种率的单价疫苗可以允许非目标人群在疫苗提供比自然感染更弱的免疫力时复活。此外，作为大流行模拟的代理，我们分析了一种逃避自然免疫的变种的入侵。我们发现，未来的疫苗在足够高的疫苗接种率下提供足够广泛和长寿命的跨群体保护，可以防止大流行的出现并减轻大流行的负担。这项研究强调，除了有效性之外，对于未来的人类甲型流感疫苗，应在流行病学知情的TPPs中考虑宽度和持续时间。
