Prevalence of Influenza B/Yamagata Viruses From Season 2012/2013 to 2021/2022 in Italy as an Indication of a Potential Lineage Extinction

Abstract

Background: Influenza B/Yamagata viruses exhibited weak antigenic selection in recent years, reducing their prevalence over time and requiring no update of the vaccine component since 2015. To date, no B/Yamagata viruses have been isolated or sequenced since March 2020.

Methods: The antibody prevalence against the current B/Yamagata vaccine strain in Italy was investigated: For each influenza season from 2012/2013 to 2021/2022, 100 human serum samples were tested by haemagglutination inhibition (HAI) assay against the vaccine strain B/Phuket/3073/2013. In addition, the sequences of 156 B/Yamagata strains isolated during the influenza surveillance activities were selected for analysis of the haemagglutinin genome segment.

Results: About 61.9% of the human samples showed HAI antibodies, and 21.7% had protective antibody levels. The prevalence of antibodies at protective levels in the seasons between the isolation of the strain and its inclusion in the vaccine was between 11% and 25%, with no significant changes observed in subsequent years. A significant increase was observed in the 2020/2021 season, in line with the increase in influenza vaccine uptake during the pandemic. Sequence analysis showed that from 2014/2015 season onward, all B/Yamagata strains circulating in Italy were closely related to the B/Phuket/2013 vaccine strain, showing only limited amino acid variation.

Conclusions: A consistent prevalence of antibodies to the current B/Yamagata vaccine strain in the general population was observed. The prolonged use of a well-matched influenza vaccine and a low antigenic diversity of B/Yamagata viruses may have facilitated a strong reduction in B/Yamagata circulation, potentially contributing to the disappearance of this lineage.

Keywords: Yamagata lineage; humoral immunity; influenza B virus.

FIGURE 1

Prevalence of antibodies against influenza B/Phuket/3073/2013 virus from 2012/2013 to 2021/2022 influenza season. Blue line with circles indicates prevalence of HAI titres ≥ 10, while red line with squares indicates prevalence of HAI titres ≥ 40. B/Yamagata vaccine strains by season are indicated in boxes. Dotted line indicates influenza vaccine coverage for general population according to the Italian Ministry of Health [14].

FIGURE 2

Median HAI titres against influenza B/Phuket/3073/2013 virus from 2012/2013 to 2021/2022 influenza season. Dots represent individual values, and bars represent median with IQR.

FIGURE 3

Prevalence of antibodies against influenza B/Phuket/3073/2013 virus from 2012/2013 to 2021/2022 influenza season by age group: 18–64 years old (a) and ≥ 65 years old (b). Blue line with circles indicates prevalence of HAI titres ≥ 10, while red line with squares indicates prevalence of HAI titres ≥ 40. B/Yamagata vaccine strains by season are indicated in boxes. Dotted line indicates influenza vaccine coverage (data available only for elderly) according to the Italian Ministry of Health [14].

FIGURE 4

Median HAI titres against influenza B/Phuket/3073/2013 virus from 2012/2013 to 2021/2022 influenza season by age group: 18–64 years old (a) and ≥65 years old (b). Dots represent individual values, and bars represent median with IQR.

FIGURE 5

Phylogenetic tree of the HA protein sequences from influenza B/Yamagata lineage viruses detected in Italy from 2012/2013 to 2017/2018. The analysis includes 156 sequences of isolates and the three recommended vaccine strain (B/Wisconsin/1/2010, B/Massachusetts/2/2012, B/Phuket/3073/2013, marked in bold). Clades were marked and mainly characterizing amino acid substitutions in comparison with B/Wisconsin/1/2010 vaccine strain were reported (coloured dots, see legend in the figure). * not showing the L172Q substitution; # not showing N116K, K298E, E312K substitutions.