IMMUNE IMPRINTING IN INFLUENZA: CELLULAR MECHANISMS, CLINICAL SIGNIFICANCE, AND PROSPECTS FOR NEXT – GENERATION VACCINE DEVELOPMENT

Abstract

Influenza viruses remain a major cause of seasonal morbidity and mortality worldwide, while the effectiveness of current influenza vaccines depends not only on the antigenic match between vaccine and circulating strains but also on an individual’s immunological history. One of the key mechanisms shaping both infection- and vaccine-induced immunity is immune imprinting, historically described as Original Antigenic Sin (OAS). The aim of this review was to summarize current knowledge on the cellular and molecular mechanisms of immune imprinting in influenza, evaluate its clinical and epidemiological significance, and discuss its implications for the development of next-generation influenza vaccines. This narrative review was based on publications retrieved from the PubMed, Scopus, and Web of Science databases. Particular attention was paid to the roles of memory B cells, long-lived plasma cells, germinal centers, and T follicular helper cells in the establishment and maintenance of immunological memory. The review also examines the influence of antigenic distance between sequential influenza strains on the effectiveness of naturally acquired and vaccine-induced immunity and highlights recent advances in antigen engineering aimed at reshaping pre-existing immune memory. Current evidence indicates that immune imprinting is a fundamental property of adaptive immunity that may either enhance broad cross-protective immunity or restrict the generation of novel immune specificities, depending on the antigenic context. Recent developments in vaccine engineering, systems immunology, and high-throughput immune profiling provide new opportunities for the design of universal influenza vaccines capable of rationally modulating immunological memory while inducing durable and broadly protective immune responses