Extent of immune history shapes the antibody response against the influenza virus in a mouse model

Antigenic imprinting refers to the effects of prior exposures on subsequent immune responses to antigenically related viral strains and the human immune history influences the magnitude and quality of future antibody responses. However, the impact of age-dependent immune history on the antibody response to the 2009 H1N1 virus remains largely elusive, primarily due to the complexity of human experiences with infection and vaccination. Moreover, how the extent of immune history affects antibody response is unclear. In this study, we investigated the antigenic imprinting effect on hemagglutinin (HA) and neuraminidase (NA) by utilizing a mouse model, sequentially infecting them with pre-2009 seasonal H1N1 viruses and challenging them with 2009 H1N1 virus. We assessed HA- and NA-specific antibodies both before and after subjecting different groups of mice to the 2009 H1N1 viral challenge. Intriguingly, our findings show that the extent of prior infection experience influences the functional antibody response to both HA and NA against antigenically drifted or shifted strains. Furthermore, our additional experiments revealed that the pattern of antigenic imprinting for HA and NA is different across different virus strains. In conclusion, this study underscores how the extent of prior infection experiences can determine the quality and specificity of antibody responses. These findings are vital for developing more effective strategies for vaccination and antiviral treatments.