--- title: "An evolving virus. A year-round challenge." description: "Explore how influenza changes, why vaccines are regularly updated, and what science is uncovering about broader, longer-lasting protection." url: https://www.ncage.org/en/influenza language: en site: nCage Therapeutics --- # An evolving virus. A year-round challenge. Explore how influenza changes, why vaccines are regularly updated, and what science is uncovering about broader, longer-lasting protection. _A guide to influenza: the virus, how it changes, what that does to vaccines, and what the evidence actually shows. Every figure on this page links to the document it came from._ ## Four virus types, two of which matter for seasonal epidemics Influenza is an acute respiratory infection caused by influenza viruses. It is not “a bad cold”: it has a distinct virus, a distinct seasonal pattern and a measurable burden of hospitalization and death. **Influenza A** — Subtyped by two surface proteins, hemagglutinin (H) and neuraminidase (N): 18 H and 11 N subtypes are known. The two subtypes now circulating routinely in people are A(H1N1) and A(H3N2). Only influenza A viruses are known to have caused pandemics. [cdc-types, who-factsheet] **Influenza B** — Not divided into subtypes but into two lineages, B/Victoria and B/Yamagata. B/Yamagata viruses have not been detected by global surveillance after March 2020 (see Science and discovery). [cdc-types, who-rec-2026-27] **Influenza C** — Usually causes mild illness and is not considered a public-health problem; it does not cause epidemics. [who-factsheet, cdc-types] **Influenza D** — Primarily infects cattle and is not known to infect or cause illness in people. It was first isolated from pigs in Oklahoma in 2011 and has seven genome segments. [who-factsheet, cdc-types, hause-2013] Influenza A and B viruses carry their genome as eight separate segments of RNA rather than one continuous strand. The two proteins studding the outside — hemagglutinin, which binds the virus to cells, and neuraminidase, which releases new particles — are what the immune system mostly “sees” and what the vaccine mostly targets. [krammer-2018, cdc-change] The virus spreads easily from person to person, mainly in infectious droplets when people cough or sneeze, and indirectly through respiratory secretions on hands and surfaces; aerosol transmission also plays a role. The incubation period is about two days, ranging from one to four. [who-factsheet, ecdc-factsheet] Virus is found in nose and throat samples from about one day before symptoms start to five to seven days after — so people are infectious before they know they are ill. [ecdc-factsheet] ### Typical symptoms - Sudden onset of fever - Cough, usually dry, which can last two weeks or more - Headache - Muscle and joint pain - Severe malaise (feeling unwell) - Sore throat and runny nose ### Complications Most people recover within a week without medical care, but severe cases can involve pneumonia, myocarditis (inflammation of the heart muscle) or encephalitis, and secondary bacterial pneumonia is a typical complication. The risk of severe disease is highest in older people and in those with chronic conditions. [who-factsheet, ecdc-factsheet] ### Groups at higher risk - Pregnant women - Children under five - Older people - People with chronic medical conditions - People with weakened immune systems - Health workers (higher exposure, and risk of onward transmission) ## Why does the flu vaccine need updating? Seven connected diagrams, from the virus particle to the vaccine calendar. Step through them in order, switch between plain language and scientific detail, and open the sources behind any statement. Nothing in this module is a simulation of real numbers: where a picture is conceptual, it is labeled as such. _How to read these diagrams: they show mechanisms, not measurements. Shapes and distances are chosen for clarity, not drawn to scale, and no diagram predicts how well a particular vaccine will work in a particular person._ ### A · Explore the virus — The parts that matter for infection, immunity and evolution An influenza particle is a small envelope studded with two kinds of protein spikes and carrying its genetic instructions inside as eight separate pieces. Select a part to see what it does and why it matters for vaccines. Influenza A and B are enveloped, negative-sense RNA viruses with a segmented genome (eight segments). Hemagglutinin (HA) mediates receptor binding and membrane fusion; neuraminidase (NA) cleaves sialic acid to release progeny virions. HA is the immunodominant target of neutralizing antibodies, and the head domain of HA tolerates far more amino-acid change than the stem. [krammer-2018, cdc-change, cdc-types] ### B · Antigenic drift — Changing recognition, one substitution at a time As the virus copies itself, small errors accumulate in the genes for its surface proteins. Most of these changes make no difference to whether your antibodies still recognize the virus. Occasionally, a change lands in exactly the spot an antibody grips — and recognition weakens. That is antigenic drift. Antigenic drift is the accumulation of point mutations in HA and NA genes. Genetic change and antigenic change are not the same thing: antigenic evolution of A(H3N2) has been shown to be more punctuated than genetic evolution, with a small number of substitutions occasionally producing a disproportionately large antigenic effect (“cluster transitions”). Recognition by existing antibodies is a matter of degree, measured as reduced titres, not a switch. [cdc-change, smith-2004] ### C · Antigenic shift — Reassortment: when whole segments are swapped Because the genome comes in separate pieces, two different influenza A viruses infecting the same cell can produce offspring that mix their pieces. If the result carries a surface protein most people have never met, it is a major, abrupt change — antigenic shift — and it is how pandemics can begin. It is rare, and most reassortment events go nowhere. Antigenic shift is an abrupt, major change in an influenza A virus that results in a new HA, or new HA and NA, in viruses infecting humans. It can arise by reassortment of genome segments during co-infection or by direct animal-to-human transmission. The 2009 H1N1 pandemic virus is the most recent example. Shift is distinct from drift and is not the reason seasonal vaccine composition is reviewed each year; drift is. [cdc-change, cdc-2009] ### D · Multiple circulating viruses — Several viruses, changing share, different places There is never just one “flu” in circulation. A(H1N1)pdm09, A(H3N2) and influenza B/Victoria circulate at the same time, and which one dominates changes from month to month and region to region. A vaccine has to cover all of them, chosen months before anyone knows which will lead. The WHO report for the 2026–27 northern hemisphere recommendation covers 1 September 2025 to early February 2026. Influenza A predominated overall; A(H3N2) subclade K (previously J.2.4.1) predominated in most regions, A(H1N1)pdm09 circulated globally without predominating in any region, and all characterized influenza B viruses belonged to the B/Victoria lineage. Proportions varied between and within transmission zones over the period. [who-rec-2026-27, who-flunet] ### E · The selection timeline — From surveillance to a needle, with a forecast in the middle Twice a year — February for the northern hemisphere, September for the southern — WHO convenes experts to look at what has been circulating and recommend what next season’s vaccine should contain. Manufacturers then need the intervening months to produce and distribute it. The catch: the decision is made before the season it is meant for, so it is a forecast. GISRS, created by WHO in 1952, now comprises 152 National Influenza Centres in over 129 countries conducting year-round surveillance, with WHO Collaborating Centres and Essential Regulatory Laboratories characterizing viruses. The consultation is held in February (northern) and September (southern); in the United States, FDA’s advisory committee makes the national decision in February or March. Northern-hemisphere vaccination then runs from autumn into a winter season. [cdc-selection, who-rec-2026-27, who-recs-index, cdc-timeline] ### F · Match and protection — Antigenic match is not the same as vaccine effectiveness Whether the vaccine viruses “match” what is circulating is one factor in how well vaccination protects — but only one. Age, what your immune system has met before, how long ago you were vaccinated and which outcome you count (any infection, a doctor’s visit, a hospital stay) all change the answer. Choose the factors to see what the evidence says about each. Antigenic match is assessed in the laboratory with ferret antisera and human serology; vaccine effectiveness (VE) is estimated epidemiologically, most often with test-negative designs, and varies by virus type and subtype, age group, time since vaccination and outcome. A well-matched season does not guarantee high VE against A(H3N2), and VE can be moderate even when the match is imperfect. [belongia-2016, ferdinands-2017, cdc-ve, who-rec-2026-27] ### G · Why not one permanent vaccine? — Variable targets, conserved targets, and what is being tried The part of the virus that antibodies find easiest to attack is also the part that changes fastest. Parts that change slowly exist, but the immune system tends to ignore them. Researchers are testing ways to point immunity at those steadier targets. Several approaches are in early human trials; none is yet shown to give broad, lasting protection. The HA head is immunodominant and highly variable; the HA stem is relatively conserved across subtypes within a phylogenetic group but subdominant. Immune imprinting from the first childhood infection shapes later responses. NIAID’s 2018 strategic plan set criteria for a “universal” vaccine; candidates such as a group 2 stabilized-stem ferritin nanoparticle have completed phase 1 safety and immunogenicity trials. No candidate has demonstrated clinical efficacy against multiple subtypes over multiple seasons. [krammer-2018, gostic-2016, erbelding-2018, casazza-2024] ### Reviewed every year, changed when the evidence calls for it WHO-recommended egg-based vaccine viruses for three consecutive northern-hemisphere seasons. Between 2024–25 and 2025–26 only the A(H3N2) component changed; for 2026–27 all three changed, after ferret antisera and human sera against the 2025–26 viruses showed poor recognition of the newly predominant A(H3N2) subclade K. [who-rec-2026-27, who-rec-2025-26, who-rec-2024-25] ### What would count as “universal”? - At least 75% effective against symptomatic influenza - Protects against both group 1 and group 2 influenza A viruses - Durable protection for at least one year - Suitable for all age groups [erbelding-2018] Putting the module together: influenza viruses accumulate genetic change continuously, and some of that change alters what antibodies recognize (drift). Several types and subtypes circulate at once, with a shifting balance across regions and months. Vaccine composition has to be recommended months before the season it serves, on the basis of what is circulating at the time — so it is a forecast, and forecasts sometimes miss. Meanwhile, the protection a vaccine gives fades over months and depends on age, prior exposure and subtype. [cdc-change, who-rec-2026-27, cdc-selection, ferdinands-2017, belongia-2016] That is why the composition is reviewed every year and updated when needed, and why annual vaccination is recommended even in years when nothing changes — two different reasons that are often conflated. A vaccine that made both unnecessary would have to aim at the conserved parts of the virus; that work is under way and, as of September 2026, still in early clinical stages. [cdc-keyfacts, cdc-change, erbelding-2018, casazza-2024] ## Large numbers, mostly modeled Influenza deaths are rarely recorded as such on death certificates, so headline burden figures are estimates produced by models from surveillance data. This section keeps observations and estimates apart and says what each number is a denominator of. ### Worldwide (WHO) - Cases of seasonal influenza each year: ≈ 1 billion - Cases of severe illness: 3–5 million - Respiratory deaths: 290 000 – 650 000 Annual estimates from WHO’s fact sheet (updated 28 February 2025). The death figure counts respiratory deaths only and is a modeled range; deaths from cardiovascular and other complications are not included. WHO also notes that 99% of deaths in children under five with influenza-related lower-respiratory infections occur in developing countries. [who-factsheet] ### European Union / EEA (ECDC) - Symptomatic cases each year: up to 50 million - Deaths each year: 15 000 – 70 000 From ECDC’s factsheet (last updated 12 April 2022). The wide range reflects season-to-season variation and modeling uncertainty. ECDC does not publish a season-by-season series comparable to the US one below, so none is charted here. [ecdc-factsheet] In temperate climates, seasonal epidemics occur mainly during winter; in tropical regions influenza may occur throughout the year, with outbreaks that are more irregular. In Europe, epidemics generally fall between November and April. [who-factsheet, ecdc-factsheet] Season size varies several-fold: CDC’s US estimates range from 9.4 million symptomatic illnesses in 2011–12 to 51 million in 2024–25 (preliminary). The 2020–21 season, during COVID-19 restrictions, had too little influenza to estimate at all. [cdc-burden] ### A world map is deliberately missing Country-level influenza surveillance differs enormously in testing intensity, so mapping raw FluNet counts would mostly show where testing happens, not where influenza is. Rather than draw a misleading map, this page links to WHO’s FluNet, where positivity and type/subtype data can be explored country by country with the surveillance context attached. ## Several technologies, one recommendation, a menu of antivirals All statements about approvals and recommendations here refer to the United States for the 2026–27 season unless stated otherwise, because that is where the most complete public documentation exists. Products and age indications differ in the EU and elsewhere. **Egg-based inactivated (IIV3)** — Candidate vaccine viruses are grown in embryonated hens’ eggs, inactivated and purified. The oldest and still the most widely used method; an inactivated vaccine was licensed for civilian use in 1945. US 2026–27: Fluarix, FluLaval (GSK); Fluzone and Fluzone High-Dose (Sanofi). Ages 6 months and over; High-Dose 65 and over. Growing viruses in eggs can introduce egg-adapted changes that make the vaccine virus differ from circulating viruses; a 2017 study attributed reduced 2016–17 effectiveness against A(H3N2) in part to a glycosylation site absent from the egg-adapted strain. [cdc-vax-summary, cdc-timeline, cdc-cell-based, zost-2017] **Cell-culture inactivated (ccIIV3)** — Viruses are grown in mammalian cell lines instead of eggs; since 2019–20 all candidate viruses used in Flucelvax are cell-derived, avoiding egg adaptation. US 2026–27: Flucelvax (Seqirus), ages 6 months and over. CDC notes cell-based production might allow faster start-up in a pandemic because cells can be banked and frozen; the page gives no timeline comparison. [cdc-cell-based, cdc-vax-summary] **Recombinant (RIV3)** — The HA protein is produced directly by recombinant methods; no candidate vaccine virus is needed and there is no egg adaptation. US 2026–27: Flublok (Sanofi), ages 9 and over. Preferentially recommended, alongside high-dose and adjuvanted vaccines, for adults 65 and over in US guidance. [cdc-vax-summary, cdc-vaccine-types] **Adjuvanted (aIIV3)** — An egg-based inactivated vaccine formulated with an adjuvant to strengthen the immune response in older adults. US 2026–27: Fluad (Seqirus), ages 65 and over. One of the three preferentially recommended options for adults 65 and over. [cdc-vax-summary, cdc-vaccine-types] **Live attenuated (LAIV3)** — Weakened viruses given as a nasal spray. US 2026–27: FluMist (AstraZeneca), ages 2 through 49. Not for people 50 and over or under 2 in the US. [cdc-vax-summary, cdc-vaccine-types] **mRNA (new in 2026)** — mRNA encoding HA is delivered in lipid nanoparticles, as in COVID-19 vaccines. US: mFLUSIVA (Moderna), approved 5 August 2026 for adults 50 and over; company states it expects availability for the 2026–27 season. Under review in the EU, Canada and Australia (company-reported). Not yet listed on CDC’s 2026–27 vaccine summary as of 1 September 2026. Approval for those 65 and over is accelerated and contingent on post-marketing evidence. [moderna-mflusiva, biopharmadive-mflusiva, cdc-vax-summary] For 2026–27, WHO recommended trivalent vaccines containing A/Missouri/11/2025 (H1N1)pdm09-like, A/Darwin/1454/2025 (H3N2)-like and B/Tokyo/EIS13-175/2025 (B/Victoria)-like viruses for egg-based products, with different reference viruses for cell-, recombinant- and nucleic-acid-based products. All US vaccines have been trivalent since 2024–25, when the B/Yamagata component was removed. [who-rec-2026-27, cdc-trivalent, cdc-vaccine-types] ### How well vaccines work is measured after the fact CDC estimates effectiveness each season with a test-negative design: among people seeking care for respiratory illness, it compares vaccination rates in those who test positive for influenza with those who test negative, adjusting for site, age, sex, underlying conditions and time from onset to enrollment. [cdc-ve] ### Antiviral treatment Four antivirals are FDA-approved and recommended by CDC (page dated 10 March 2026). CDC recommends starting treatment as soon as possible for hospitalized patients, those with severe or progressive illness and those at higher risk; for otherwise healthy outpatients, within two days of onset. EU indications differ. [cdc-antivirals, who-rec-2026-27] - Oseltamivir (Tamiflu) — Neuraminidase inhibitor, Oral. Treatment from 14 days; prophylaxis from 1 year (US label) - Zanamivir (Relenza) — Neuraminidase inhibitor, Inhaled. Treatment from 7 years; prophylaxis from 5 years; not for people with underlying airway disease - Peramivir (Rapivab) — Neuraminidase inhibitor, Intravenous. Treatment from 6 months; not recommended for prophylaxis - Baloxavir marboxil (Xofluza) — Cap-dependent endonuclease (polymerase) inhibitor, Oral, single dose. Treatment and post-exposure prophylaxis from 5 years CDC describes resistance among circulating viruses as currently very low but able to change; reduced susceptibility has emerged in immunocompromised patients and in children treated with baloxavir. WHO’s February 2026 report found no evidence of reduced baloxavir susceptibility among the B/Victoria viruses examined. ## Findings that changed how influenza is understood ### A whole lineage of influenza B appears to have vanished No confirmed detections of circulating B/Yamagata lineage viruses have been recorded anywhere in global surveillance after March 2020. [who-rec-2026-27, cdc-trivalent, cdc-types] **Why it matters:** It is the reason vaccines went from four components to three: WHO stopped recommending a B/Yamagata component and all US vaccines became trivalent from 2024–25. It is also a natural experiment in how pandemic-era measures affect virus populations. **What it cannot tell us:** Absence of detections is not proof of extinction; surveillance has gaps, and WHO’s wording is deliberately “no confirmed detections”. ### Antigenic change is jumpier than genetic change By placing viruses on an “antigenic map” from ferret antisera data, Smith and colleagues showed in 2004 that A(H3N2) evolved antigenically in clusters, with punctuated jumps, while genetic change was gradual; some single substitutions had a disproportionately large antigenic effect. [smith-2004] **Why it matters:** It explains why counting mutations does not tell you whether a vaccine still matches, and it underpins the way WHO and its collaborating centers monitor drift today. **What it cannot tell us:** The study covers A(H3N2) from 1968 to 2003; antigenic cartography depends on ferret antisera, which do not fully reproduce human immune histories. ### Your first childhood flu shapes your defenses for life Using all known human cases of H5N1 and H7N9, Gostic and colleagues found that a person’s first influenza A infection confers lifelong protection against severe disease from novel HA subtypes in the same phylogenetic group: 75% against severe infection and 80% against death. [gostic-2016] **Why it matters:** Any broadly protective vaccine will act on an immune system already imprinted; birth year, not just age, predicts who is vulnerable to which subtype. **What it cannot tell us:** Statistical inference from case age distributions, not a mechanistic demonstration; applies to avian subtypes and does not by itself predict seasonal vaccine responses. ### Eggs can quietly change the vaccine virus Contemporary A(H3N2) viruses carry a glycosylation site in antigenic site B that the egg-adapted 2016–17 vaccine strain lacked; antibodies raised by that egg-grown strain poorly neutralized the glycosylated circulating virus. [zost-2017, who-rec-2026-27] **Why it matters:** Part of the case for cell-based and recombinant vaccines, which avoid egg adaptation, and part of why WHO now names separate reference viruses for egg- and non-egg-based products. **What it cannot tell us:** The authors propose that egg adaptation “likely contributed” to reduced effectiveness that season; the size of that contribution is not quantified. ### Protection from a seasonal vaccine fades within the season In US network data pooled over 2011–12 to 2014–15, effectiveness fell by about 7 percentage points per month for A(H3N2) and B and 6–11 per month for A(H1N1)pdm09, while remaining above zero for at least five to six months. [ferdinands-2017, cdc-keyfacts] **Why it matters:** One of the two reasons annual vaccination is recommended, separate from the reason composition is reviewed; it also informs when campaigns should start. **What it cannot tell us:** Observational data from one network and four seasons; the rate of waning varied by subtype and was steeper in people vaccinated the previous season. ### A fourth influenza type, found in pigs In 2011 a novel orthomyxovirus with seven RNA segments, about 50% amino-acid identity to human influenza C, was isolated from pigs in Oklahoma; it is now classified as influenza D and is mainly found in cattle. [hause-2013, who-factsheet] **Why it matters:** A reminder that the influenza family is larger than the two types that cause human epidemics, and that surveillance in animals is part of pandemic preparedness. **What it cannot tell us:** Influenza D is not known to infect or cause illness in people. ### Stem-directed antibodies can be raised in people A first-in-human phase 1 trial of a group 2 HA stabilized-stem ferritin nanoparticle vaccine (25 adults) was safe and induced stem-binding and neutralizing antibodies that stayed above baseline at 40 weeks, including cross-reactive H3 and H7 binding. [casazza-2024] **Why it matters:** It is the kind of result a broadly protective vaccine would need first — but only first. **What it cannot tell us:** Open-label, 25 participants, no efficacy endpoint; immunogenicity is not protection. ### Milestones - **1918** — The H1N1 pandemic. An H1N1 virus with genes of avian origin infected about 500 million people — a third of the world’s population — and killed at least 50 million worldwide, about 675 000 in the United States (historical estimates). [cdc-1918] - **1945** — First inactivated vaccine licensed for civilians. Inactivated influenza vaccine is licensed for civilian use in the United States. [cdc-timeline] - **1952** — WHO creates GISRS. The Global Influenza Surveillance and Response System is created to monitor the evolution of influenza viruses; it now comprises 152 National Influenza Centres in over 129 countries. [cdc-timeline, cdc-selection] - **1957** — The H2N2 pandemic. A new H2N2 virus emerges; about 1.1 million deaths globally and about 116 000 in the United States (historical estimates). [cdc-timeline] - **1968** — The H3N2 pandemic. A new H3N2 virus emerges; roughly 1 million deaths worldwide and 100 000 in the United States. Descendants of this virus still circulate as seasonal A(H3N2). [cdc-timeline, smith-2004] - **2004** — Antigenic cartography. The antigenic evolution of A(H3N2) from 1968 to 2003 is mapped and shown to proceed in punctuated clusters. [smith-2004] - **2009** — The H1N1pdm09 pandemic. A novel H1N1 virus is first detected in the United States in spring 2009. CDC estimates 151 700–575 400 deaths worldwide in its first year; WHO declares the pandemic over on 10 August 2010. Its descendants are today’s seasonal A(H1N1)pdm09. [cdc-2009] - **2011** — Influenza D isolated. A novel influenza virus, later designated type D, is isolated from pigs in Oklahoma. [hause-2013] - **2018** — NIAID universal-vaccine strategic plan. NIAID publishes criteria and a research plan for a universal influenza vaccine. [erbelding-2018] - **2020** — Last confirmed B/Yamagata detection. No confirmed circulating B/Yamagata viruses are detected after March 2020. [who-rec-2026-27] - **2024** — Vaccines return to three components. US vaccines become trivalent from the 2024–25 season after the B/Yamagata component is dropped. [cdc-trivalent] - **2026** — First mRNA seasonal influenza vaccine approved. FDA approves mFLUSIVA for adults 50 and over on 5 August 2026 (company announcement). [moderna-mflusiva, biopharmadive-mflusiva] ## What can be verified about the influenza vaccine market This section reports only what audited filings, company results announcements and regulatory documents say. Commercial market-size forecasts are not reproduced: their methods are opaque and they are not evidence. **Who makes the vaccines used in the United States** — For 2026–27, CDC lists products from four manufacturers: GSK (Fluarix, FluLaval), Sanofi (Fluzone, Fluzone High-Dose, Flublok), Seqirus (Flucelvax, Fluad) and AstraZeneca (FluMist). Moderna’s mFLUSIVA was approved on 5 August 2026 and is not yet on that list as of 1 September 2026. [cdc-vax-summary, moderna-mflusiva] **Sanofi: influenza and COVID-19 vaccines, 2025** — Company-reported: full-year 2025 sales of the “Influenza, COVID-19” vaccines line were €2 314 million, down 5.8% at constant exchange rates, of which €1 328 million in the United States. Fourth-quarter sales rose 31.5% to €575 million, which Sanofi attributed to more circulating virus and a higher vaccination rate than anticipated. The line combines influenza and COVID-19 products; an influenza-only figure is not disclosed. [sanofi-fy2025] **CSL Seqirus: fiscal 2025 and a planned demerger** — Company-reported, year to 30 June 2025: CSL Seqirus revenue US$2 166 million, up 2% at constant currency; Fluad sales US$901 million (down 14%) and Flucelvax US$474 million (down 12%), which CSL attributed to significantly lower immunization rates, particularly in the US, partly offset by about US$150 million of H5 avian-influenza pandemic-preparedness contracts. CSL announced its intention to demerge Seqirus as an ASX-listed company before the end of its fiscal 2026. [csl-fy2025] **Technology trend: away from eggs, and now mRNA** — Cell-based, recombinant and adjuvanted products carry US preferential recommendations for older adults, and the first mRNA seasonal vaccine was approved in August 2026. Whether these shift market share is not something this page can verify from public filings, and it does not claim to. [cdc-vax-summary, moderna-mflusiva] **Independent market sizing** — No independent, methodologically transparent estimate of the global influenza vaccine market was identified among the sources reviewed for this page. Figures circulated by commercial research firms are proprietary and were not used. _Company figures are as reported by the companies, in their own segment definitions and currencies, and are not audited by this page. Sanofi reports in euros at constant exchange rates; CSL in US dollars at constant currency; the two are not comparable._ ## How this page was made Source selection. Factual statements are supported by, in order of preference: WHO and national public-health agencies (CDC, ECDC); regulatory documents; peer-reviewed research identified by DOI; audited company filings and results announcements for market information; and trade press only for reporting of very recent events where the primary document was not yet indexed. Each source was opened and read on 12 September 2026, and the date shown next to it is the source’s own publication or last-updated date. Data transformations. None. The two charted series (CDC US burden by season; CDC US vaccine effectiveness by season) were transcribed from the published figure and table respectively, without interpolation, smoothing or combination with other datasets. Seasons the source does not estimate (2020–21) are stored as missing and drawn as a gap. Values are point estimates; CDC publishes uncertainty intervals for burden in its full tables, which are not reproduced in the summary figure used here, so the burden chart shows no intervals. The effectiveness chart shows the 95% confidence intervals exactly as published. Assumptions and limitations. US data are used for charts because they are the most complete open, season-by-season series with stated methods; they do not represent Europe or the world. Surveillance intensity differs between countries, which is why no map is drawn. Vaccine effectiveness estimates are population statistics from specific study designs and are not individual predictions. The interactive diagrams are conceptual and are labeled as such; the vaccine-match explorer only surfaces quoted findings and does not compute anything. Evidence labels. “Established finding” is used for results published in peer-reviewed journals or by public-health agencies and not, to the page authors’ knowledge, contradicted by later work. “Modeled estimate” marks numbers produced by statistical models rather than counts. “Emerging evidence” marks early-phase or single-study results. “Forecast or scenario” marks statements about the future. “Evidence gap” marks where reliable information was sought and not found. Update policy. Statements about approvals, recommendations and products are dated and jurisdiction-specific; they will go out of date. The page should be re-checked before each northern-hemisphere season, at minimum against the WHO February recommendation and CDC’s September vaccine summary. ## Every source used on this page - [who-factsheet] World Health Organization. Influenza (seasonal) — fact sheet. 2025-02-28. https://www.who.int/news-room/fact-sheets/detail/influenza-(seasonal) - [cdc-types] US Centers for Disease Control and Prevention. Types of influenza viruses. 2025-09-26. https://www.cdc.gov/flu/about/viruses-types.html - [cdc-change] US Centers for Disease Control and Prevention. How flu viruses can change: “drift” and “shift”. 2024-09-17. https://www.cdc.gov/flu/php/viruses/change.html - [cdc-selection] US Centers for Disease Control and Prevention. Selecting viruses for the seasonal influenza vaccine. 2026-09-01. https://www.cdc.gov/flu/vaccine-process/vaccine-selection.html - [cdc-keyfacts] US Centers for Disease Control and Prevention. Key facts about seasonal flu vaccine. 2026-09-01. https://www.cdc.gov/flu/vaccines/keyfacts.html - [cdc-ve] US Centers for Disease Control and Prevention. CDC seasonal flu vaccine effectiveness studies (past seasons’ estimates). 2026-03-16. https://www.cdc.gov/flu-vaccines-work/php/effectiveness-studies/index.html - [cdc-burden] US Centers for Disease Control and Prevention. About estimated flu burden — estimated US influenza burden by season, 2010–2025. 2026-02-25. https://www.cdc.gov/flu-burden/php/about/index.html - [cdc-vaccine-types] US Centers for Disease Control and Prevention. Different types of flu vaccines. 2026-09-01. https://www.cdc.gov/flu/vaccine-types/index.html - [cdc-vax-summary] US Centers for Disease Control and Prevention. Interim clinical considerations for the use of seasonal influenza vaccines in the United States, 2026–27. 2026-09-01. https://www.cdc.gov/flu/hcp/vax-summary/seasonal-influenza-vaccines.html - [cdc-trivalent] US Centers for Disease Control and Prevention. Trivalent influenza vaccines. 2026-05-11. https://www.cdc.gov/flu/vaccine-types/trivalent.html - [cdc-cell-based] US Centers for Disease Control and Prevention. Cell-based flu vaccines. 2023-08-25. https://www.cdc.gov/flu/vaccine-types/cell-based.html - [cdc-antivirals] US Centers for Disease Control and Prevention. Influenza antiviral medications: summary for clinicians. 2026-03-10. https://www.cdc.gov/flu/hcp/antivirals/summary-clinicians.html - [cdc-1918] US Centers for Disease Control and Prevention (archived page). 1918 pandemic (H1N1 virus). 2019-03-20. https://archive.cdc.gov/www_cdc_gov/flu/pandemic-resources/1918-pandemic-h1n1.html - [cdc-2009] US Centers for Disease Control and Prevention (archived page). 2009 H1N1 pandemic (H1N1pdm09 virus). 2019-06-11. https://archive.cdc.gov/www_cdc_gov/flu/pandemic-resources/2009-h1n1-pandemic.html - [cdc-timeline] US Centers for Disease Control and Prevention (archived page). Influenza historic timeline, 1930 and beyond. 2019-01-30. https://archive.cdc.gov/www_cdc_gov/flu/pandemic-resources/pandemic-timeline-1930-and-beyond.htm - [who-rec-2026-27] World Health Organization. Recommended composition of influenza virus vaccines for use in the 2026–2027 northern hemisphere influenza season (full report). 2026-02-27. https://www.who.int/publications/m/item/recommended-composition-of-influenza-virus-vaccines-for-use-in-the-2026-2027-northern-hemisphere-influenza-season - [who-rec-2025-26] World Health Organization. Recommendations announced for influenza vaccine composition for the 2025–2026 northern hemisphere influenza season. 2025-02-28. https://www.who.int/news/item/28-02-2025-recommendations-announced-for-influenza-vaccine-composition-for-the-2025-2026-northern-hemisphere-influenza-season - [who-rec-2024-25] World Health Organization. Recommendations announced for influenza vaccine composition for the 2024–2025 northern hemisphere influenza season. 2024-02-23. https://www.who.int/news/item/23-02-2024-recommendations-announced-for-influenza-vaccine-composition-for-the-2024-2025-northern-hemisphere-influenza-season - [who-recs-index] World Health Organization. WHO recommendations on the composition of influenza virus vaccines (index). 2026-02-27. https://www.who.int/teams/global-influenza-programme/vaccines/who-recommendations - [who-flunet] World Health Organization, Global Influenza Surveillance and Response System. FluNet — global influenza surveillance data. 2026-09-12. https://www.who.int/tools/flunet - [ecdc-factsheet] European Centre for Disease Prevention and Control. Factsheet about seasonal influenza. 2022-04-12. https://www.ecdc.europa.eu/en/seasonal-influenza/facts/factsheet - [belongia-2016] Belongia EA, Simpson MD, King JP, et al.. Variable influenza vaccine effectiveness by subtype: a systematic review and meta-analysis of test-negative design studies. Lancet Infect Dis 2016;16(8):942–951. 2016-08-01. https://doi.org/10.1016/S1473-3099(16)00129-8 - [ferdinands-2017] Ferdinands JM, Fry AM, Reynolds S, et al.. Intraseason waning of influenza vaccine protection: evidence from the US Influenza Vaccine Effectiveness Network, 2011–12 through 2014–15. Clin Infect Dis 2017;64(5):544–550. 2017-03-01. https://doi.org/10.1093/cid/ciw816 - [smith-2004] Smith DJ, Lapedes AS, de Jong JC, et al.. Mapping the antigenic and genetic evolution of influenza virus. Science 2004;305(5682):371–376. 2004-07-16. https://doi.org/10.1126/science.1097211 - [gostic-2016] Gostic KM, Ambrose M, Worobey M, Lloyd-Smith JO. Potent protection against H5N1 and H7N9 influenza via childhood hemagglutinin imprinting. Science 2016;354(6313):722–726. 2016-11-11. https://doi.org/10.1126/science.aag1322 - [zost-2017] Zost SJ, Parkhouse K, Gumina ME, et al.. Contemporary H3N2 influenza viruses have a glycosylation site that alters binding of antibodies elicited by egg-adapted vaccine strains. Proc Natl Acad Sci USA 2017;114(47):12578–12583. 2017-11-21. https://doi.org/10.1073/pnas.1712377114 - [hause-2013] Hause BM, Ducatez M, Collin EA, et al.. Isolation of a novel swine influenza virus from Oklahoma in 2011 which is distantly related to human influenza C viruses. PLoS Pathog 2013;9(2):e1003176. 2013-02-07. https://doi.org/10.1371/journal.ppat.1003176 - [krammer-2018] Krammer F, Smith GJD, Fouchier RAM, et al.. Influenza. Nat Rev Dis Primers 2018;4:3. 2018-06-28. https://doi.org/10.1038/s41572-018-0002-y - [erbelding-2018] Erbelding EJ, Post DJ, Stemmy EJ, et al.. A universal influenza vaccine: the strategic plan for the National Institute of Allergy and Infectious Diseases. J Infect Dis 2018;218(3):347–354. 2018-07-02. https://doi.org/10.1093/infdis/jiy103 - [casazza-2024] Casazza JP, Hofstetter AR, Costner PJM, et al. (VRC 323 study team). Phase 1 dose-escalation trial evaluating a group 2 influenza hemagglutinin stabilized stem nanoparticle vaccine. npj Vaccines 2024;9:171. 2024-09-17. https://doi.org/10.1038/s41541-024-00959-0 - [sanofi-fy2025] Sanofi. Press release: 2025 — strong sales and EPS growth; continued profitable growth expected in 2026 (full-year results). 2026-01-29. https://www.sanofi.com/assets/dotcom/pressreleases/2026/2026-01-29-06-30-00-3228191-en.pdf - [csl-fy2025] CSL Limited. ASX announcement: FY25 results and major strategic initiatives. 2025-08-19. https://investors.csl.com/pdf/56bf77f4-8eff-40ff-bb67-c890e3a3476e/CSL-FY25-Results-and-Major-Strategic-Initiatives.pdf - [moderna-mflusiva] Moderna, Inc. (via Nasdaq). Moderna receives U.S. FDA approval for influenza vaccine mFLUSIVA (press release). 2026-08-05. https://www.nasdaq.com/press-release/moderna-receives-us-fda-approval-influenza-vaccine-mflusiva-2026-08-06 - [biopharmadive-mflusiva] BioPharma Dive. FDA approves Moderna’s mRNA flu vaccine. 2026-08-06. https://www.biopharmadive.com/news/moderna-fda-approve-mflusiva-seasonal-influenza/826864/