# The Persistence of Cross-Reactive Immunity to Influenza B/Yamagata Neuraminidase Despite the Disappearance of the Lineage: Structural and Serological Evidence

## TL;DR

The study found that immunity to the influenza B/Yamagata lineage persists even after it stopped circulating, possibly due to cross-reactive antibodies from other influenza B strains.

## Contribution

The study provides structural and serological evidence for the persistence of cross-reactive immunity to B/Yamagata neuraminidase despite its disappearance.

## Key findings

- Antibody levels to B/Yamagata neuraminidase remained high in 2023 despite no recent infections.
- Antibodies to B/Yamagata and B/Victoria neuraminidase correlated in older individuals, suggesting antigenic sin.
- Cross-reactive antibodies may offer broad protection between influenza B lineages.

## Abstract

Influenza B viruses, divided into B/Victoria and B/Yamagata lineages, have not had B/Yamagata isolates after 2020. A study evaluated immunity to influenza B surface antigens hemagglutinin (HA) and neuraminidase (NA) in 138 patient sera from 2023 and 23 pairs of sera from 2018 to 2019 vaccine recipients. The phylogenetic tree of the influenza B virus, based on HA and NA genes, shows that the Yamagata lineage evolves gradually, while the Victoria lineage exhibits rapid mutations with short branches. In 2023, mean levels of antibodies to HA and NA of B/Yamagata virus were higher than to B/Victoria, despite no cases of B/Yamagata lineage isolation after 2020. The titers of antibodies to NA of B/Yamagata statistically significantly differed among individuals born before and after 1988. Among patients examined in 2018–2019, neuraminidase-inhibiting (NI) antibody titers before vaccination were higher to B/Yamagata than to B/Victoria, and NI antibodies to B/Victoria and B/Yamagata positively correlated with neutralizing antibodies to B/Victoria virus before and after vaccination. Immunity to B/Yamagata virus was stronger in 2023, despite no isolation since 2020, probably due to the presence of cross-reactive antibodies from B/Victoria infections or vaccinations. Antibodies to NA of B/Victoria and B/Yamagata in 2023 correlated significantly in patients born before 1988, potentially supporting the concept of ‘antigenic sin’ phenomenon for influenza B viruses. The fact that NI antibody titers to B/Victoria and B/Yamagata correlated with neutralizing antibody titers to B/Victoria may suggest broad cross-protection. Studying influenza B virus NA antigenic properties helps understand the evolution and antigenic competition of HA and NA.