(J-396) Probing immune imprinting and memory recall within an influenza vaccine trial

Introduction:: Immune imprinting is a phenomenon in which the immune system retains a memory of a previous encounter with a pathogen, leading to enhanced protection against future infections. It has been shown that vaccination can induce immune imprinting, but the duration and efficacy of this effect remain unclear. In this study, we aim to investigate the long-term immune imprinting effects in the context of influenza vaccination. Using statistical and machine learning models, we systematically analyzed serological data collected from a clinical trial where volunteers were vaccinated with split, inactivated Fluzone influenza vaccine in four consecutive influenza seasons from 2013 to 2016 seasons.


Materials and Methods:: We recruited healthy volunteers from different age groups (18-30, 40-60, and 60+) and collected blood samples pre- and post- Fluzone vaccination. We quantified the antibodies induced by the vaccine, using hemagglutination inhibition (HAI) assays, enzyme-linked immunosorbent assays (ELISAs) and high-throughput Systems Serology. We implemented powerful statistical methods (Mann-Whitney U test, Wilcoxon test and ANOVA) and machine learning models (partial least squared regression and partial least squared discriminative analysis), to evaluate the breadth of repeated vaccination of the pandemic strain H1N1 CA09 at genetic, protein and systems level.


Results, Conclusions, and Discussions:: Our results suggested that repeated vaccination of the pandemic strain H1N1 CA09 gradually broaden the coverage of vaccine-induced immunity against other major H1N1 strains. It is noteworthy that additional computational analysis revealed that neither age nor the route (intramuscular or intradermal) or dose of vaccine administration had a detrimental effect on the breadth of immunity induced by the repeated vaccination. This study provides valuable insights into the long-term immune imprinting effects of vaccination and can inform future vaccine development strategies in influenza. The integrative computational approach performed in this study provides a useful framework for other infectious disease research, particularly those where immune imprinting poses a challenge in developing vaccines that confer broad immunity.


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