Journal Article

The impact of egg adaptation and immune imprinting on influenza vaccine effectiveness

Youhanna, John, McGovern, Ian, Rajaram, Sankarasubramanian, Rockman, Steven, Stein, Alicia N., McMahon, Meagan, Ashraf, Mansoor, Miller, Matthew S.

2025

Overview

Most influenza vaccines are produced in hens' eggs and may undergo ‘egg adaptation’, whereby mutations within the haemagglutinin protein that result in adaptation to the avian cells undergo positive selection. It is well established that egg adaptation can impact antigenicity and vaccine effectiveness (VE) by causing mismatches between the vaccine virus and circulating viruses. However, few studies have investigated the potentially long-lasting impact of childhood vaccination with an egg-adapted vaccine on the immunological memory. Prior exposure history shapes subsequent immune responses, such that memory responses to previously encountered antigens trigger stronger immune responses than those elicited by de novo antigen exposure. This phenomenon is called immune imprinting, when referring specifically to the impact of the first lifetime exposure, and antigenic seniority, when referring to exposures after the first, which also shape an individual's antibody repertoire according to how early and how often they are encountered. Crucially, if an individual's first influenza exposure is via an egg-adapted vaccine, this imprinting event could adversely affect antibody responses to circulating viruses in future seasons, reducing the benefit of influenza vaccination. Using alternative types of vaccines that avoid egg adaptation is particularly important now that the World Health Organization (WHO) recommend immunising children aged ≥6 months against influenza. In this review, we cover the historical frequency and nature of egg adaptations and the impact of egg adaptation, immune imprinting and antigenic seniority on the clinical effectiveness of seasonal influenza vaccinations. We discuss the impact of interactions between egg adaptation and immune imprinting, examine how egg-adapted vaccines can lead to suboptimal imprinting and potentially reduce VE throughout an individual's lifetime, and identify how we can address this issue in future. [Display omitted] •A person's first exposure to influenza has a life-long impact on immune response.•To improve effectiveness, vaccine viruses should closely match circulating strains.•Egg adaptations can alter the antigenicity of the vaccines and reduce effectiveness.•Egg adaptations have been identified in most egg-based influenza vaccine viruses.•Childhood immunisation with non-egg-based vaccines could optimise immune imprinting.

• Publisher: Elsevier Ltd,Elsevier Limited
• Subject: Adaptation / Adaptation, Physiological / Allergy and Immunology / Animals / Antibodies / Antibodies, Viral - immunology / Antigenic seniority / Antigenicity / Antigens / Avian cells / Avian flu / birds / Cell-based vaccines / Chickens / childhood / Children / chronic exposure / Effectiveness / Egg-adapted mutations / Eggs / Eggs - virology / Exposure / Hemagglutinins / Humans / Immune imprinting / Immune response / Immune system / Immunologic Memory / Immunological memory / Immunology / Infections / Influenza / influenza vaccination / influenza vaccines / Influenza Vaccines - immunology / Influenza, Human - immunology / Influenza, Human - prevention & control / memory / Mutation / Positive selection / Seniority / Vaccination / Vaccine effectiveness / Vaccine Efficacy / Vaccines / Viruses / World Health Organization