The Spanish flu emerged in 1918 and was identified as the influenza A H1N1 virus. In 1940, the first outbreak of respiratory illness occurred in children, with clinical signs similar to those of the influenza A virus (IAV). This lead to the identification of a new virus, named the influenza B virus (Francis Jr, 1940). It is now understood that influenza A and B viruses co-circulate among the human population across different age groups with varying degrees of severity. Unlike the influenza A virus, the influenza B virus has no established animal reservoir and poses no pandemic risk (Jackson et al., 2011). The influenza B virus can pose significant challenges during annual epidemics, yet it often receives less attention compared to other strains, while influenza C and D are not as prevalent. According to the WHO and CDC, influenza causes approximately 650,000 deaths each year, with the influenza B virus contributing to 20 to 30% of these fatalities. The purpose of this review is to provide a comprehensive analysis of influenza B, focusing on its epidemiology, genetic evolution, and impact on public health. Understanding the significance of influenza B is crucial due to its substantial role in seasonal flu epidemics, particularly affecting vulnerable populations such as children and the elderly, and the ongoing challenges it presents in vaccine development after the low prevalence of B/Yamagata and public health management (Figure 1).

The influenza B virus has segmented, negative-sense, single-stranded RNA composed of 8 segments. It includes three surface glycoproteins (HA, NA, and NB), a BM2 ion channel, a nuclear export protein (sometimes referred to as BNS2 or NEP), a matrix protein (BM1), a nonstructural protein (NS1), and a nucleoprotein (NP), which encodes three polymerase proteins (PB1, PB2, and PA). The virus belongs to the Orthomyxoviridae family (Palese, 2007). The influenza A virus is classified into various subtypes based on the combination of hemagglutinin (HA) and neuraminidase (NA) surface proteins, leading to substantial antigenic variation and the potential for pandemics. Influenza A has 18 HA subtypes (H1 to H18) and 11 NA subtypes (N1 to N11). The most significant influenza subtypes are H1N1 and H3N2, which contribute to various epidemics and pandemics (Shao et al., 2017). Influenza B virus does not have accessory proteins PA-X or PB1-F2 while influenza A has these proteins (Krumbholz et al., 2011; Shi et al., 2012). The proteins of influenza A and B show differences in composition, length, and functions (Jackson et al., 2011). Influenza A virus has various subtypes while influenza B viruses have been divided into two antigenically and genetically different lineages: B/Yamagata/16/1988-like and B/Victoria/2/1987-like virus (Rota et al., 1990; McCullers et al., 2004; Vijaykrishna et al., 2015).

Influenza viruses are a significant cause of morbidity and mortality worldwide, posing major public health challenges. Among these, two types of influenza viruses circulate widely in human populations: influenza A and influenza B. Influenza A viruses, particularly the A (H3N2) subtype, are known for their widespread impact (McCullers and Hayden, 2012), are generally associated with higher rates of hospitalization and mortality compared to influenza B, the latter still significantly contributes to the global influenza disease burden, causing approximately one-third of global influenza cases each year and severe disease, especially in children (Yang et al., 2012). Influenza B viruses are classified into two distinct lineages: B/Yamagata/16/88 (Yamagata lineage) and B/Victoria/2/87 (Victoria lineage) (Kanegae et al., 1990). These lineages emerged in the 1970s and have co-circulated globally since at least 1983, with both lineages alternating in regional dominance (Kanegae et al., 1990). The differentiation is marked by HA features, and by 1988, 27 amino acid (a.a.) differences were noted in the HA1 domains of these lineages (Rota et al., 1990). Minimal a.a. changes were observed in the HA2 domains at that time, and phylogenetic analysis indicated separate lineages for the HA2 domains of both B/Yamagata/16/88-like and B/Victoria/2/87-like viruses (Rota et al., 1992). Genome-wide analyses suggest that reassortment plays a crucial role in the evolution of influenza B viruses, with frequent exchanges observed between the Yamagata and Victoria lineages across all eight gene segments (Chen and Holmes, 2008). Despite the slower pace of antigenic change in influenza B compared to influenza A, the Victoria lineage experiences more rapid lineage turnover, exhibiting distinct epidemiological patterns such as longer persistence in local regions before wider dissemination. Victoria-lineage viruses tend to show faster antigenic drift rates, averaging 3.9 to 5.1 years, whereas the Yamagata lineage has an average antigenic drift rate of 6.3 to 7.2 years (Langat et al., 2017). Nonetheless, Yamagata viruses tend to infect an older population and exhibit an epidemiological pattern of alternating antigenic dominance between seasons (Figure 2).

The evolutionary patterns of these lineages reveal that Yamagata-lineage viruses consist of two coexisting clades: clade 2 (B/Massachusetts/02/2012) and clade 3 (B/Wisconsin/1/2010) (Skowronski et al., 2014). In contrast, Victoria-lineage viruses have diversified into two dominant monophyletic clades (clades 1A and 1B) since 2011 (Langat et al., 2017). The PB1 and PB2 phylogenetic trees display considerable divergence akin to the HA gene, with the PB1, PB2, and HA genes consistently originating from a singular lineage (Dudas et al., 2015). Historically, influenza B virus epidemics have been sporadic compared to influenza A, but recent years have seen significant changes, with substantial epidemics reported globally, such as the high activity observed in Europe in 2015 (Barr et al., 2016). Since 2001, both influenza B lineages have been co-circulating worldwide during each epidemic season. They can coexist in different proportions within the same season and in specific regions (Chen and Holmes, 2008). Most studies suggest that the B/Victoria lineage is more prevalent than the B/Yamagata lineage in younger populations (Yang et al., 2018). A comprehensive analysis conducted using the Global Influenza B Surveillance (GIBS) database has highlighted significant differences in the age demographics affected by B/Victoria and B/Yamagata influenza infections. The findings reveal that B/Yamagata infections predominantly affect older age groups compared to B/Victoria. In most countries studied, B/Victoria infections are primarily found in younger individuals, typically between 0 to 25 years old, with a notable peak among children under 10 years of age. On the other hand, B/Yamagata infections often exhibit a bimodal age distribution pattern. This means there are two distinct peaks in infection rates: one among children under 10 years old and another, albeit smaller, among adults aged 25 to 50 years (Yang et al., 2018).

The introduction of quadrivalent vaccines, which include strains from both influenza B lineages, has been recommended to mitigate issues often seen with trivalent vaccines that cover only one lineage. This limitation frequently results in reduced vaccine effectiveness (Tisa et al., 2016). Efforts to develop a universal vaccine capable of targeting both B lineages are a critical public health priority. Recent research indicates that both lineages have undergone selective sweeps preceding resurgences. Victoria-lineage viruses have shown more pronounced changes in the HA gene, including nucleotide deletions, and have co-evolved with neuraminidase (NA) and internal gene segments. In contrast, Yamagata-lineage viruses exhibit stronger seasonal fluctuations due to antigenic drift in the NA protein. While antibody cross-protection between the two B lineages is generally considered low, some studies suggest significant levels of cross-reactive serum antibodies (Skowronski et al., 2011). Experimental evidence indicates that vaccination with the B/Yamagata lineage can induce cross-antibody responses to the Victoria lineage, though the reverse is less effective. Studies involving B-cell memory and monoclonal antibodies (mAbs) derived from individuals vaccinated with the quadrivalent seasonal vaccine (IIV-4) have confirmed the immunological dominance of B/Yamagata HA (Liu et al., 2019).

The 1889–1890 Russian flu emerged in 1889 and lasted for four years in 4 waves. The Russian flu was caused by Myxovirus and lately confirmed as influenza H2N2 (Berche, 2022a). It caused 257 million deaths in 1890, 574,000 in 1891 and 534,000 in 1892 (Honigsbaum, 2011). The 1918–1919 Spanish flu was caused by influenza A virus H1N1. It caused 50–100 million deaths (Berche, 2022b). The 1957–1958 Asian flu was caused by an H2N2 strains of influenza A virus. While influenza B co-circulated during this period but their role was minor as compared to influenza A (MacKellar, 2007). The 1968–1969 Hong Kong flu caused by H3N2 strain of influenza A virus. Influenza B did not play a significant role in this period but co-circulate in this season (Tang et al., 2008). The 1977 Russian flu was caused by the reemergence by a novel H1N1 strain of influenza A virus similar to the 1918 virus. Influenza B did not contribute to this epidemic (Kalyar et al., 2024). The 2009–2011 Swine flu mainly caused by H1N1 (Lim and Mahmood, 2011). The cases of IBV infection can vary rapidly during the influenza season (Toback et al., 2012). In a period between 1985 and 2000, a single influenza B virus lineage, B/Yamagata in the 1990s and B/Victoria in the late 1980s, dominated the season of influenza, but after 2001, both lineages have been spreading in the southern and northern hemispheres (Bodewes et al., 2011; Sauerbrei et al., 2014; Paul Glezen et al., 2013; Kim et al., 1979). In 20th century, influenza B virus caused 23.4% cases in each flu season. In the Netherlands, the B/Yamagata lineage has spread every influenza season between the periods of 1999 and 2007, except for the season of 2002–2003. The B/Victoria lineage spread from 2001 to 2006, except in 2004 (Thompson et al., 2004). Early thoughts suggested that IBV causes a less severe disease than IAV. However, the rates of mortality, morbidity, and hospitalization (except during the IAV pandemic) did not support this evidence. (Thompson et al., 2004). IBV is normally thought to be less severe as compared to IAV/H3N1 but more severe than IAV/H1N1 in the last ten years (Thompson et al., 2004; Thompson et al., 2010; McCullers and Hayden, 2012; Claas et al., 1995; Grant et al., 2009; Kawai et al., 2011). IBV causes disease in a population of all age groups, and the disease is spreading more among young adults and children. B/Yamagata lineage causes more infection in the young age group as compared to B/Victoria (McCullers and Hayden, 2012). According to the CDC report, IBV accounted for 34% of influenza deaths during the period between 2004–2005 and 2009–2010, except for the pandemic of 2009 (Thompson et al., 2010). From the Netherlands data, a 29% ratio of IBV was detected in respiratory samples from the period of 1992–1993 to 2006–2007 (Dijkstra et al., 2009). In the Netherlands, an analysis performed with serum samples taken from 720 children showed that 72% of the children at the age of 7 years had developed antibodies against IBV, which is indicative of a high attack rate (Bodewes et al., 2011). On the other side, in Germany, a seroprevalence study conducted from 2008 to 2010 indicated that 47% of individuals under the age of 17 developed specific IgG antibodies against IBV (Sauerbrei et al., 2014). Data from 12 pediatric hospitals in Canada between 2004 and 2013 indicated that the mortality rate among hospitalized patients (aged ≤16 years) with influenza B (1,510 cases) was higher compared to those with influenza A (2,645 cases), with 16 deaths (1.1%) for influenza B and 10 deaths (0.4%) for influenza A (Tran et al., 2016). This study also revealed that otherwise healthy children (aged ≥10 years) infected with influenza B had a significantly higher likelihood of requiring intensive care unit (ICU) admission than those with influenza A, with an odds ratio of 5.79 (95% confidence interval 1.91–17.57). Additionally, a systematic review of 126 studies emphasized the severity of influenza B infections in children, showing that influenza B accounted for 22–44% of all influenza-related pediatric deaths from 2004 to 2011, excluding the 2009–2010 period (Paul Glezen et al., 2013). More recent data from the US (2010–2016) supports these findings, indicating that influenza B viruses were responsible for 16–52% of all influenza-associated pediatric deaths (Shang et al., 2018). Fatal cases of influenza B in children are often linked to bacterial pneumonia and cardiac injury, with the latter being a major cause of influenza B-related deaths in this age group (Paddock et al., 2012). In comparison, almost all the children at the age of 7 developed antibodies against at least one IAV strain (Toback et al., 2012; Sauerbrei et al., 2014). The seroprevalence is based on many factors, including the spreading of the influenza virus (A/H1N1, B, and A/H3N2), the endurance of the evident antibody feedback, and a geographic map showing the need for more comprehensive studies. Based on CDC data, an average of 24% of respiratory samples with infection collected in the United States from 2001–2002 to 2010–2011 (2009 is excluded because it was the pandemic year) tested positive for IBV through reverse transcriptase polymerase chain reaction (RT-PCR) (Toback et al., 2012). Surveillance data from Europe showed that an average of 23% of influenza-infected respiratory samples tested positive for IBV simultaneously (Dijkstra et al., 2009). Influenza B caused 20% of the influenza cases in each season from 2000 to 2018 in 21th century. Influenza B type contribute 20% in 118 seasons, 20 to 50% in 115 seasons and above 50% in 45 seasons. Influenza B usually peaked in August to September in the countries of the southern hemisphere 1.1 month later than influenza A. Average proportion of influenza B cases that were reported in a season caused by B/Victoria lineage. In 27 seasons out of 84, 20% co-circulation of the both the lineages were reported. While B/Victoria contributed 70% of the cases in a season while B/Yamagata reported 30% of the cases. Influenza B/Victoria infected age between 10 and 13 while B/Yamagata infected older people. The proportion of B/lineage vaccine mismatch was 42.9% in countries of the northern hemisphere and 54.2% I the countries of the southern hemisphere (Caini et al., 2019).

After 2020, B/Yamagata circulation has not been confirmed (Caini et al., 2023). In 2021, India reported 3 B/Yamagata detections, while Bulgaria, Afghanistan, Nigeria, Mexico, and the United States reported 1 B/Yamagata detection. In 2022, North Korea and Germany reported 1 B/Yamagata detection. In 2023, Cuba reported 1 B/Yamagata detection. There were many new cases reported in the early months of 2024, but none of the sequences were uploaded to GISAID. No B/Yamagata detection has been confirmed since 2021. There is a myth that influenza B/Yamagata extinct but it is too early to declare the extinction of B/Yamagata. The absence of B/Yamagata sequences post-March 2020 highlights the importance of continued molecular surveillance to monitor lineage dynamics and detect potential resurgence events. Overall, the combined analysis of epidemiological and molecular surveillance data provides valuable information on the temporal trends and dynamics of influenza activity, informing strategies for influenza prevention, control, and preparedness. According to WHO Flu Net and GISAID, Table 1 represents a summary of influenza cases in the last 5 years (GISAID, n.d.; WHO, 2024).

A sore throat, coughing, nasal discharge, and fever are signs of an IBV infection (Wright and Kawaoka, 2007). Overall, despite possible differences in consequences, IBV and IAV caused illnesses are identical (Irving et al., 2012). Neurological and muscular symptoms (Moon et al., 2013; Thabet et al., 2013), cardiologic issues (Frank et al., 2010; Paddock et al., 2012; Taremi et al., 2013), and subsequent bacterial infections (Paddock et al., 2012; Taremi et al., 2013; Aebi et al., 2010; Scaber et al., 2011) are also possible signs of IBV. The period between the commencement of the illness and death in fatal cases of influenza was shown to be shorter for IBV than for the 1918, 1957, 1968, and 2009 pandemics of IAV (Paddock et al., 2012). The influenza B virus is more prevalent in children, but it also infects older people and adults. The Victoria lineage of the influenza virus is more common in children than the Yamagata lineage. The respiratory route serves as an entry point for the influenza B virus into the body, predominantly through inhaling respiratory droplets that carry the virus. These droplets are produced during activities such as coughing, sneezing, or talking by an infected individual (Kutter et al., 2018). Infected individuals can spread the from 1 day before symptoms appear and up to 7 days after becoming sick. The virus attaches to the respiratory epithelial cells lining the airways, primarily in the nose and throat. The viral surface protein called hemagglutinin binds to specific receptors on the surface of the host cells. The virus then enters the cells using receptor-mediated endocytosis. Once inside the host cell, the virus releases its genetic material, which is in the form of eight single-stranded RNA segments (Matsuoka et al., 2013; Kapoor et al., 2014). The viral RNA serves as a template for the synthesis of new viral proteins and the replication of the viral genome. This process occurs in the host cell’s nucleus. The newly synthesized viral proteins and RNA segments are assembled to form new virus particles. These viral particles then exit the host cell by budding from the cell membrane or causing the cell to burst (lysis) (Chauhan and Gordon, 2022). The released virus can infect neighboring cells, leading to the spread of infection throughout the respiratory tract. The infection triggers an immune response in the body. The immune system recognizes the presence of the virus and initiates an inflammatory response to control the infection. Immune cells, such as macrophages and natural killer cells, target and eliminate infected cells. The adaptive immune response, involving B cells and T cells, produces antibodies that can neutralize the virus and help clear the infection (Figure 3).

The replication cycle begins when the virus accesses the columnar epithelial cells of the respiratory tract, overcoming the protective mucus layer by using its neuraminidase (NA) glycoprotein to cleave mucin and sialic acid. The hemagglutinin (HA) glycoprotein then binds the virus to the exposed epithelial cells, facilitating endocytosis via clathrin and caveolin-dependent mechanisms. Within the acidic environment of the lysosome, the viral matrix protein (M1) dissociates from the ribonucleoprotein (RNP) complex, releasing viral RNA that is subsequently imported into the host cell nucleus for replication (Mohsan Ullah Goraya and Munir, 2015).

Influenza A virus circulates among humans and various other wild animals, including dogs, pigs, horses, and chickens. Nevertheless, IBV has been isolated from diverse species such as grey seals (Halichoerus grypus), harbor seals (Phoca vitulina), and dogs (Canis lupus familiaris), understanding the virus’s ability to infect these animals (Chang et al., 1976; Leyva-Grado et al., 2012). Moreover, serological evidence confirms IBV infection in specific animal species residing in close proximity to humans. These species include guinea pigs (Cavia porcellus), dogs (Canis lupus familiaris), pigs (Sus domesticus), ruminants (Bornean orangutans) (Pongo pygmaeus), horses (Equus ferus caballus), western lowland gorillas, western common chimpanzees (Pan troglodytes verus), and zoo birds (Horimoto et al., 2014; Brown et al., 1995; Kawano et al., 1978; Buitendijk et al., 2014; Romvary et al., 1980; Ran et al., 2015; Ohishi et al., 2002; Bodewes et al., 2013). Distinct antibodies specific to IBV have been identified in various species of wild pinnipeds, such as grey seals (Halichoerus grypus), Caspian seals (Phoca caspica), South American fur seals (Arctocephalus australis), and harbor seals (Phoca vitulina). However, these antibodies have not been detected in harbor porpoises (Phocoena phocoena) (Bodewes et al., 2014; Blanc et al., 2009). Although IBV demonstrates the ability to infect certain wild species, there is no evidence of transmission to humans. Influenza B virus isolated from seals in Netherland but no evidence of transmission from seals to human observed. Influenza B virus continue to infect seals and support the notion that seals could be reservoir for influenza B virus (Bodewes et al., 2013). The primary specific reason influenza B virus does not have an extensive animal reservoir is its host specificity. Unlike influenza A virus, which has the ability to infect a wide range of species due to its diverse subtypes and high genetic variability, influenza B virus is primarily adapted to humans and, to a lesser extent, seals. It has been shown that influenza B virus also susceptible to pigs. A serological study indicated that influenza B antibodies detected in 7.3% of tested swine herds (Ran et al., 2015). Influenza B virus also detected from the respiratory tract of ferrets and pigs (Pica et al., 2012; Elderfield et al., 2015). There are certain reason influenza B does not have animal reservoir. Firstly, influenza B viruses have evolved to bind specifically to receptors found in the human respiratory tract. This receptor binding specificity limits their ability to infect and replicate in other species, as different animals may have different types of receptors that influenza B cannot efficiently bind to. Secondly, Influenza B virus has less genetic diversity compared to influenza A. This limits its ability to adapt to and evolve in different animal hosts. The genetic makeup of influenza B is fine-tuned for human hosts, reducing its ability to spill over into other species. Finally, influenza A viruses can undergo antigenic shift, where different subtypes reassort their gene segments, potentially creating new viruses that can infect new host species. Influenza B does not have this capability, which limits its ability to jump to and establish itself in new animal hosts. Influenza B host range is currently not well understood or may likely expand over time (Jang and Seong, 2020).

The study of the pathogenicity of influenza B virus infection indicates the importance of employing experimental model animals to analyze vaccine protective efficiency and immunogenicity in the context of human disease. Numerous studies involving IBV have been conducted on various animal models, including ferrets (Mustela putorius furo) and mice (Mus musculus). Additionally, pigs, guinea pigs, dogs, Syrian golden hamsters (Mesocricetus auratus), cynomolgus macaques (Macaca fascicularis), and cotton rats (Sigmodon hispidus) have been practically inoculated with various IBV strains, as detailed in Table 2 (Ran et al., 2015; Huang et al., 2014; Ottolini et al., 2005; Song et al., 2015; Rarey et al., 1987; Kim et al., 2009; Maassab et al., 1982; Pica et al., 2012; Hirst, 1947; Pica et al., 2011; Davis et al., 1990; Davis, 1987; Takatsy and Romvary, 1969; Reeve and Gerendas, 1981; Kitano et al., 2010). Virus multiplication has been observed in all laboratory animals except for dogs, and a specific experimental study in pigs demonstrated pig-to-pig circulation infected with B/Victoria strains (Ran et al., 2015). Clinical signs were widely observed, and the severity of the disease was contingent on the IBV strains employed for inoculation (Huang et al., 2014; Pica et al., 2012; Davis, 1987). In the 1980s and 1990s, a mouse-adapted human IBV strain (B/Lee/40) was introduced to experimental mice to examine IBV’s characteristics in the progression of Reye’s syndrome in children (Davis, 1987). Through intravenous inoculation, mice exhibited numerous pathological, clinical, and virological features identical to those observed in children with Reye’s syndrome. The titration of IBV was also scrutinized in ferrets (Deshmukh, 1985; Rarey et al., 1984; Mukhopadhyay et al., 1992; Rarey, 1985).

Influenza B viruses are a significant cause of respiratory illness, particularly in children. The host immune response to the influenza B virus is critical for controlling the infection and preventing severe disease. This discussion aims to cover the immunology of influenza B viruses, encompassing the innate and adaptive immune responses, along with the current understanding of protection mechanisms and immune evasion (Figure 4).

There are two types of approved anti-influenza B drugs: neuraminidase inhibitors (NAIs) like zanamivir and oseltamivir, and adamantanes such as rimantadine and amantadine. Adamantanes inhibit the activity of the ion channel AM2, but not BM2. This is due to specific amino acid residues in the BM2 ion channel, which, being polar, decrease the drug’s access to the ion channel pore (Ma et al., 2008). As a result, adamantanes are ineffective against IBV. NAIs can inhibit IBV replication. The high degree of catalytic site conservation between IAV and IBV can be used to explain why NAIs have an inhibitory effect on both IAV and IBV. Burnham et al. (Burnham et al., 2014) have published a thorough study on the effectiveness of NAIs and the resistance mutations of IBVs. Oseltamivir is less effective in treating influenza B virus compared to its effectiveness against influenza A virus. On the other hand, zanamivir shows similar effectiveness against both influenza B virus and influenza A virus. Clinical isolates, surveillance isolates, and reverse genetics investigations all contain mutations that confer resistance to NAIs. Both the catalytic region of the enzyme (like R152K) and the framework residues (like D198N and I222T) might contain these changes. Contrary to the majority of resistance mutations, studies on the fitness cost of NAI-resistant mutations have demonstrated that the E119A and H274Y mutations have little effect on viral replication and fitness (Burnham et al., 2014). A new drug, baloxavir marboxil, has been developed against influenza A and B. This drug acts as a polymerase inhibitor that acts on influenza A and B. It’s interesting to note that distinct mutations in the NA gene from the two IBV lineages appear to have varied frequencies and effects (Farrukee et al., 2015).

Influenza B virus (IBV) stands as a significant pathogen in the history of respiratory illnesses, demanding continual research and vigilance to combat its impact on human health. The recent reported cases of influenza B highlight the decline in influenza B/Yamagata and the possibility of extinction. Therefore, it’s compulsory to review the new detection, prevention, and vaccine policies. This review highlights the various aspects of IBV, from its evolution and phylodynamic to diagnostic techniques, immunology, and antiviral strategies. IBV’s evolutionary history has been a fascinating topic of study because it has shown that it is capable of undergoing genetic alterations that can result in the formation of new strains and seasonal variations. Understanding the phylodynamic of the virus helps public health officials predict and prepare for potential outbreaks, as well as select the most suitable vaccine strains to include in seasonal influenza vaccines. Accurate and prompt diagnosis plays a crucial role in managing IBV cases effectively. The advent of advanced diagnostic techniques such as real-time PCR, RT-PCR, microassay, pyrosequencing, NASBA, LAMP, CRISPR and NGS has revolutionized the detection process, allowing for rapid identification of IBV strains and early intervention.

The immunology of IBV is a complex area of research, highlighting the interplay between the virus and the human immune system. Understanding the host immune response is critical to developing effective vaccines and antiviral therapies that can target IBV and reduce its impact on vulnerable populations. Moreover, antiviral strategies against IBV have seen significant advancements, with ongoing research into novel therapeutic approaches and the development of antiviral agents. Prophylactic measures, including annual influenza vaccination, play a pivotal role in mitigating the severity of IBV infections and preventing complications. Compared to influenza A, the greatest risk of influenza B to humans lies in its potential to cause severe illness in specific populations, such as children and the elderly, and its ability to co-circulate with influenza A, complicating prevention and treatment efforts. Despite the focus on influenza A due to its pandemic potential, studying influenza B is equally important as it contributes significantly to the annual flu burden, requires distinct vaccine considerations due to its two lineages, and poses unique challenges in public health, particularly in predicting and controlling seasonal outbreaks. As we conclude, it is clear that the influenza B virus remains a persistent public health concern worldwide. Collaborative efforts between virologists, immunologists, epidemiologists, and public health officials are essential in advancing our understanding of the virus and improving our preparedness to face future outbreaks. Continued research into IBV’s evolution, diagnostics, and immunology will empower us to stay one step ahead of the virus, safeguarding the well-being of global populations and reducing the burden on healthcare systems during influenza seasons.