Fifteen Years of Surveillance Reveal Influenza B Lineage Shift in Riyadh

Influenza B virus has long lived in the shadow of its influenza A counterpart, attracting less attention from researchers and public health authorities despite its capacity to cause substantial seasonal morbidity. A new study from King Saud University in Riyadh now offers one of the most detailed long-term pictures of influenza B evolution in the Arabian Peninsula, drawing on molecular surveillance data spanning 2010 to 2025. The research, published in BMC Infectious Diseases, documents a complete shift in the dominant viral lineage circulating in the Saudi capital and shows that, even as the virus continues to evolve, recent strains remain genetically close to the vaccine strains recommended by the World Health Organization.

The investigation was led by Reem M. Aljowaie, Ibrahim M. Aziz, Mohamed A. Farrag, Noorah A. Alkubaisi, Asma N. Alsaleh and Fahad N. Almajhdi of the Department of Botany and Microbiology at King Saud University. Between 2014 and 2020, the team collected 311 respiratory specimens from patients presenting with influenza-like illness in Riyadh. Each sample was screened by reverse transcription polymerase chain reaction, a molecular technique capable of detecting viral RNA with high sensitivity. Of the 311 specimens, 88, or 28.3 percent, tested positive for influenza A, while only six samples, representing 1.9 percent, were positive for influenza B virus. Although the number of influenza B detections was modest, the researchers sequenced the complete hemagglutinin and neuraminidase genes of these viruses, providing the full-length genetic data needed for rigorous evolutionary analysis.

Hemagglutinin and neuraminidase are the two surface proteins that define the antigenic identity of influenza viruses. Hemagglutinin mediates entry into host cells and is the principal target of neutralizing antibodies, while neuraminidase facilitates the release of newly formed viral particles. Mutations accumulating in these proteins can alter antigenic properties and, by extension, the degree of protection conferred by vaccination. The Riyadh team recorded mutations at both the nucleotide and amino acid levels, mapped N-linked glycosylation sites, and compared their sequences against WHO vaccine reference strains. They also generated six influenza B isolates from the 2014 to 2020 specimens and incorporated 31 previously published Riyadh sequences covering 2010 through 2025, allowing the analysis to extend across a decade and a half of local viral evolution.

The phylogenetic results revealed a clear lineage replacement event. Viruses belonging to the B/Yamagata lineage were detected in Riyadh in 2015, whereas samples from 2020 belonged exclusively to the B/Victoria lineage. Influenza B viruses are divided into these two genetically and antigenically distinct lineages, which co-circulated globally for decades before the B/Yamagata lineage dramatically declined after the COVID-19 pandemic. The Riyadh dataset mirrors this global pattern: among the sequenced isolates available for the full 2010 to 2025 period, no B/Yamagata-lineage viruses were detected in recent years, and sustained B/Victoria predominance was observed throughout the later portion of the surveillance window.

Within the B/Victoria lineage, the analysis showed that recent isolates from 2023 to 2025 carried the characteristic deletion of amino acids at positions 164 and 165 in the hemagglutinin protein. This deletion, located in or near antigenic regions of the protein, first emerged in globally circulating Victoria-lineage viruses and has become a defining feature of newer subclades. The Riyadh sequences from 2021 to 2025 all belonged to the V1A.3a.2 subclade, which has become the globally dominant form of B/Victoria. Earlier viruses in the dataset fell within subclades V1A.3 and related groups, illustrating the stepwise genetic drift that has characterized the lineage over the surveillance period.

Despite this ongoing evolution, the study found that the hemagglutinin and neuraminidase proteins of the circulating viruses were highly conserved relative to the WHO vaccine strains. Substitutions were identified in the major antigenic regions of hemagglutinin, including the 120-loop, the 150-loop, the 160-loop and the 190-helix, structural elements that antibodies recognize when they neutralize the virus. However, these changes were limited in number and did not translate into substantial genetic distance from the vaccine components. The B/Yamagata viruses from earlier years displayed lineage-specific glycosylation patterns, while the Victoria-lineage viruses maintained largely conserved N-linked glycosylation profiles, with one notable exception: some isolates showed a gain or loss of a glycosylation site at hemagglutinin position 197, a change that could potentially influence antigenicity and deserves continued monitoring.

Perhaps the most reassuring finding from a public health standpoint concerns vaccine compatibility. The researchers compared recent Riyadh isolates with the WHO-recommended vaccine strains B/Austria/1,359,417/2021 and B/Tokyo/EIS13-175/2025 and found that the local viruses remained genetically close to both, exhibiting only limited amino acid substitutions. This suggests that the influenza B component of seasonal vaccines has continued to match the viruses circulating in Riyadh, supporting the effectiveness of current vaccination strategies in the region. Because influenza B vaccine mismatch has historically contributed to reduced vaccine effectiveness in some seasons, this genetic concordance is a meaningful indicator for Saudi immunization planning.

The study also underscores the practical challenges of influenza B surveillance. With only 1.9 percent of the collected specimens testing positive for influenza B, the virus circulates at low levels in Riyadh compared with influenza A, and the number of sequences available for any given season is small. The authors are careful to frame their lineage replacement conclusion as reflecting the available surveillance dataset rather than an absolute claim of global or even national disappearance of B/Yamagata. Nevertheless, the finding aligns with international observations that B/Yamagata has not been robustly detected since around 2020, raising questions about whether the lineage may have gone extinct and whether quadrivalent vaccines, which include both B lineages, will continue to be necessary or whether trivalent formulations lacking B/Yamagata will become standard.

The research was approved by the Research Ethics Committee at King Saud University under Institutional Review Board number 14/4463/IRB 03/IRB, approved on December 3, 2014, and conducted in accordance with the Declaration of Helsinki, with informed consent obtained from all participants. The work was funded by the Ongoing Research Funding Program of King Saud University under grant ORF-2026-198. The authors declare no competing interests, and the article is published open access under a Creative Commons license.

For Saudi Arabia and the wider Middle East region, where long-term influenza B sequence data have historically been sparse, this fifteen-year record fills an important gap in the global map of influenza B evolution. The authors conclude that the predominance of B/Victoria and the non-detection of B/Yamagata within the available dataset underscore the need for continuous molecular surveillance to monitor viral evolution, assess vaccine strain compatibility, and support influenza prevention efforts in the kingdom. As influenza B continues its slow but steady genetic drift, sustained sequencing efforts in underrepresented regions such as Saudi Arabia will remain essential for ensuring that vaccine recommendations rest on a genuinely global picture of viral diversity.

Subject of Research: Long-term molecular epidemiology and genetic evolution of influenza B virus in Riyadh, Saudi Arabia, from 2010 to 2025

Article Title: Long-term molecular surveillance of influenza B virus in Riyadh, Saudi Arabia (2010–2025): lineage replacement, genetic evolution, and vaccine strain compatibility

Article References: Aljowaie, R. M., Aziz, I. M., Farrag, M. A., Alkubaisi, N. A., Alsaleh, A. N., & Almajhdi, F. N. (2026). Long-term molecular surveillance of influenza B virus in Riyadh, Saudi Arabia (2010–2025): lineage replacement, genetic evolution, and vaccine strain compatibility. BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14442-9

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14442-9

Keywords: influenza B virus, B/Victoria lineage, B/Yamagata lineage, hemagglutinin, vaccine effectiveness, phylogenetic analysis, molecular epidemiology, lineage replacement, glycosylation, Saudi Arabia, viral evolution, surveillance