Hodgson David, Sánchez-Ovando Stephany, Carolan Louise, Liu Yi, Hadiprodjo A Jessica, Fox Annette, Sullivan Sheena G, Kucharski Adam J
Center of Mathematical Modelling of Infectious Diseases, London School of Hygiene and Tropical Medicine, London, UK.
Department of Infectious Diseases, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia; WHO Collaborating Centre for Reference and Research on Influenza, Royal Melbourne Hospital, At The Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
Vaccine. 2025 Jan 12;44:126579. doi: 10.1016/j.vaccine.2024.126579. Epub 2024 Dec 5.
Epidemiological studies suggest that heterogeneity in influenza vaccine antibody response can be associated with specific host factors, including pre-vaccination immune status, age, gender, and vaccination history. However, the pattern of reported associations varies between studies. To better understand the underlying influences on antibody responses, we combined host factors and vaccine-induced in-host antibody kinetics from a cohort study conducted across multiple seasons with a unified analysis framework. We developed a flexible individual-level Bayesian model to estimate associations and interactions between host factors, including pre-vaccine HAI titre, age, sex, vaccination history and study setting, and vaccine-induced HAI titre antibody boosting and waning. We applied the model to derive population-level and individual effects of post-vaccine antibody kinetics for A(H1N1) and A(H3N2) influenza subtypes. We found that post-vaccine HAI titre dynamics were significantly influenced by pre-vaccination HAI titre and vaccination history and that lower pre-vaccination HAI titre results in longer durations of seroprotection (HAI titre equal to 1:40 or higher). We also observed that the effect of vaccination history on antibody boosting was stronger for egg-grown A(H1N1) vaccinating strains in individuals with higher pre-vaccination HAI titres, whereas this effect diminished for egg-grown A(H3N2) vaccinating strains. Consequently, for cell-grown A(H1N1), our inference finds that the expected duration of seroprotection post-vaccination was 171 (95 % Posterior Predictive Interval[PPI] 128-220) and 159 (95 % PPI 120-200) days longer for those who are infrequently vaccinated (<2 vaccines in last five years) compared to those who are frequently vaccinated (2 or more vaccines in the last five years) at pre-vaccination HAI titre values of 1:10 and 1:20 respectively. In addition, we found significant differences in the empirical distributions that describe the individual-level duration of seroprotection for A(H1N1) cell-grown strains. In future, studies that rely on serological endpoints should include the impact of pre-vaccine HAI titre and prior vaccination status on seropositivity and seroconversion estimates, as these can significantly influence an individual's post-vaccination antibody kinetics.
流行病学研究表明，流感疫苗抗体反应的异质性可能与特定宿主因素有关，包括接种前的免疫状态、年龄、性别和接种史。然而，不同研究报告的关联模式有所不同。为了更好地理解对抗体反应的潜在影响，我们将来自多个季节队列研究的宿主因素和疫苗诱导的体内抗体动力学结合起来，采用统一的分析框架。我们开发了一个灵活的个体水平贝叶斯模型，以估计宿主因素之间的关联和相互作用，包括接种前血凝抑制（HAI）滴度、年龄、性别、接种史和研究环境，以及疫苗诱导的HAI滴度抗体增强和减弱。我们应用该模型推导A（H1N1）和A（H3N2）流感亚型接种后抗体动力学的人群水平和个体效应。我们发现，接种后HAI滴度动态受到接种前HAI滴度和接种史的显著影响，接种前HAI滴度较低会导致血清保护持续时间更长（HAI滴度等于1:40或更高）。我们还观察到，对于接种前HAI滴度较高的个体，接种史对鸡蛋培养的A（H1N1）疫苗株抗体增强的影响更强，而对于鸡蛋培养的A（H3N2）疫苗株，这种影响减弱。因此，对于细胞培养的A（H1N1），我们的推断发现，接种前HAI滴度值分别为1:10和1:20时，与频繁接种者（过去五年接种2剂或更多疫苗）相比，不频繁接种者（过去五年接种少于2剂疫苗）接种后的预期血清保护持续时间分别长171天（95%后验预测区间[PPI]128 - 220）和159天（95%PPI 120 - 200）。此外，我们发现描述细胞培养的A（H1N1）株个体水平血清保护持续时间的经验分布存在显著差异。未来，依赖血清学终点的研究应包括接种前HAI滴度和既往接种状态对血清阳性和血清转化估计的影响，因为这些会显著影响个体接种后的抗体动力学。
