Influenza primary prevention
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mohammad Braizat, M.S. [2]
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Primary Prevention
Primary prevention of influenza relies on two complementary strategies: annual vaccination, which is the cornerstone intervention for all persons aged ≥6 months without contraindications, and targeted antiviral chemoprophylaxis, reserved for defined high-risk exposure scenarios rather than widespread use.[1]
Influenza Vaccination
Routine annual influenza vaccination is recommended for all persons aged ≥6 months without contraindications.[1] Several vaccine platforms are available — inactivated (IIV), recombinant (RIV), and live attenuated (LAIV) — with no preference among age-appropriate options noted by the American Academy of Pediatrics (AAP).[2] Vaccination should ideally occur by the end of October but should be continued throughout the season as long as viruses are circulating.[3] For older adults, CDC recommends vaccination in September or October and advises against administering too early due to waning immunity, which may be more pronounced in this population.[4]
Age- and Risk-Specific Vaccine Selection
- Adults aged ≥65 years: The Advisory Committee on Immunization Practices (ACIP) preferentially recommends one of three enhanced formulations — high-dose inactivated (HD-IIV), recombinant (RIV), or adjuvanted inactivated (aIIV, MF59-adjuvanted) — over standard-dose IIV. This is due to diminished immune responses to standard vaccination in this population. A network meta-analysis of 32 studies (>71 million vaccinated participants) found enhanced vaccines conferred modestly greater protection against influenza-associated hospitalization than standard-dose vaccine (pooled relative vaccine effectiveness [rVE] of 18%, 95% CI 3–32% from randomized studies; 11%, 95% CI 8–14% from observational studies), with no significant differences among HD, adjuvanted, and recombinant vaccines.[5] The pooled DANFLU-2/GALFLU (FLUNITY-HD) analysis and subsequent trials have since demonstrated HD-IIV superiority over standard-dose vaccine for hospitalization outcomes in adequately powered individually randomized trials.[6] A cluster-randomized crossover study found adjuvanted vaccine noninferior to HD-IIV for PCR-confirmed influenza and related hospitalization outcomes.[7] Reactogenicity (injection-site pain, systemic symptoms) is generally greater with enhanced formulations, but the benefit-risk balance favors enhanced vaccines in this population.[1][5]
- Solid organ transplant recipients: ACIP recommends that solid organ transplant recipients aged 18–64 years receiving immunosuppressive medications may receive HD-IIV3 or aIIV3 as acceptable options, without preference over other age-appropriate vaccines.[1]
- Children aged 6 months–8 years: Those requiring 2 doses (per prior vaccination history) should receive the first dose as soon as possible after vaccine becomes available, with the second dose ≥4 weeks later.[2]
- Immunocompromised patients: Live attenuated vaccine should not be administered; high-dose vaccine is favored in these groups where evidence supports improved immunogenicity.[3]
2025–26 Season Updates
Key updates for the 2025–26 season include revised antigenic composition, FDA approval of FluMist for self- or caregiver-administration, expansion of Flublok (RIV) to ages ≥9 years (from ≥18 years), and a new ACIP recommendation that children ≤18 years, pregnant women, and all adults receive only single-dose, thimerosal-free formulations.[1][4] Interim 2025–26 vaccine effectiveness estimates are lower than recent seasons but remain protective: 38–41% against outpatient visits and 41% against hospitalization in children/adolescents; 22–34% against outpatient visits and 30% against hospitalization in adults.[8]
Egg Allergy and Contraindications
ACIP now recommends that all persons aged ≥6 months with egg allergy of any severity, including anaphylaxis, receive influenza vaccine, using any age-appropriate formulation (egg-based or non–egg-based), with no additional safety measures required beyond those for any vaccine recipient.[1] This recommendation is based on 20 studies with no reported anaphylaxis cases (GRADE certainty: very low).[1] This supersedes older guidance that distinguished hive-only reactions from more severe egg reactions requiring special observation settings.
True contraindications/precautions include:[1]
- Severe allergic reaction (e.g., anaphylaxis) to any vaccine component or a prior dose of that vaccine — labeled contraindication.
- LAIV specifically: is not approved for and should not be given to persons aged <2 or >49 years; also contraindicated in pregnancy, immunosuppression, and several other conditions per ACIP beyond the package insert.
- History of Guillain-Barré syndrome within 6 weeks of a prior influenza vaccine dose — a precaution for all influenza vaccines.
- Moderate-to-severe acute illness (with or without fever) — general precaution, defer until resolution.
Antiviral Chemoprophylaxis
Antiviral chemoprophylaxis is not recommended for routine or widespread seasonal/pre-exposure use, to limit emergence of antiviral resistance and preserve treatment availability for high-risk or severely ill patients. It is reserved for specific postexposure scenarios:[9][10]
- High-risk persons exposed to an infectious contact during the first 2 weeks after vaccination (before immunity develops).
- Persons with severe immunodeficiency or others unlikely to respond to vaccination (e.g., on immunosuppressive therapy) after exposure.
- High-risk persons with a vaccine contraindication after exposure.
- Outbreak control in institutional settings (e.g., long-term care facilities).
A 2024 systematic review and network meta-analysis supporting WHO guideline development found moderate-certainty evidence that oseltamivir, zanamivir, and baloxavir probably reduce symptomatic influenza risk in high-risk individuals but have little important effect in low-risk populations.[10]
Evidence base for chemoprophylaxis agents:
- Oseltamivir (oral) and zanamivir (inhaled): Efficacious in randomized placebo-controlled household-contact studies.[9]
- Baloxavir: FDA-approved for post-exposure prophylaxis of influenza in patients aged ≥5 years.[11] A single dose within 48 hours of exposure to a symptomatic household contact reduced influenza incidence to 2% versus 13% with placebo (aRR 0.14) in a Japanese RCT (household members ≥5 years of age).[9]
- IV peramivir: No chemoprophylaxis data exist; FDA-approved indication is limited to treatment of acute uncomplicated influenza in patients aged ≥6 months symptomatic for ≤2 days.[11]
Practical points: Chemoprophylaxis should generally not be initiated if >48 hours have elapsed since exposure. When used, once-daily prophylactic dosing (oseltamivir/zanamivir) must be distinguished from higher treatment dosing. Close monitoring with early treatment initiation if symptoms develop is a reasonable alternative to prophylaxis in many exposed persons.[9]
Key Changes from Prior Guidance
- Egg allergy, including anaphylaxis, is no longer a reason to withhold or specially observe influenza vaccination.[1]
- Enhanced vaccines (HD, adjuvanted, recombinant) are now preferentially recommended for adults aged ≥65 years.[1]
- Solid organ transplant recipients aged 18–64 years on immunosuppressive medications may receive HD-IIV3 or aIIV3 as acceptable options.[1]
- Baloxavir is now FDA-approved for post-exposure prophylaxis in patients aged ≥5 years.[11]
Areas of Uncertainty or Controversy
- Whether HD-IIV, adjuvanted, or recombinant vaccine is superior for older adults remains unresolved; head-to-head data show no consistent superiority of one over another across seasons.[5][7][12]
- Interim 2025–26 vaccine effectiveness estimates (22–41% depending on age group and outcome) are lower than in recent prior seasons, underscoring year-to-year variability tied to antigenic match.[8]
- Optimal timing of vaccination in older adults is debated given concerns about waning immunity if given too early in the season.[3]
High-Yield Clinical Pearls
- Egg allergy of any severity is not a contraindication to any influenza vaccine — this is a frequently missed update in practice.[1]
- For adults aged ≥65 years, reach for HD-IIV, RIV, or aIIV first; if unavailable, give any age-appropriate vaccine rather than delaying.[1]
- LAIV is not approved for children <2 years or adults >49 years.[1]
- Baloxavir is FDA-approved for post-exposure prophylaxis in patients ≥5 years; oseltamivir and zanamivir are used off-label for this indication.[11]
- Antiviral chemoprophylaxis window closes at 48 hours post-exposure — after this, favor close symptom monitoring plus early treatment-dose therapy if illness develops.[9]
- Never use once-daily prophylactic antiviral dosing to treat a symptomatic patient — this constitutes under-dosing.[9]
Common Pitfalls
- Withholding LAIV or IIV from egg-allergic patients or requiring extended observation — no longer indicated.[1]
- Using antiviral chemoprophylaxis broadly/indiscriminately, risking resistance and depleting supply needed for treatment of high-risk or severely ill patients.[9]
- Giving LAIV to contraindicated groups (age <2 years, >49 years, pregnancy, immunosuppression).[1]
- Delaying vaccination while awaiting "ideal timing" — vaccination should proceed as soon as vaccine is available and continue throughout the season.[3]
References
- ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 1.14 1.15 Grohskopf LA, Blanton LH, Ferdinands JM; et al. (2025). "Prevention and Control of Seasonal Influenza With Vaccines: Recommendations of the Advisory Committee on Immunization Practices - United States, 2025-26 Influenza Season". MMWR. Morbidity and Mortality Weekly Report. 74 (32): 500–507. doi:10.15585/mmwr.mm7432a2.
- ↑ 2.0 2.1 American Academy of Pediatrics (2024). "Influenza". Red Book: 2024–2027 Report of the Committee on Infectious Diseases: 511–522.
- ↑ 3.0 3.1 3.2 3.3 Lutz MK, Caldera F (2025). "Vaccination Outcomes and Recommendations Among Older Adults in a Gastroenterology and Hepatology Practice". The American Journal of Gastroenterology. 120 (Suppl 10): S67–S75. doi:10.14309/ajg.0000000000003641.08.
- ↑ 4.0 4.1 "2025–2026 Flu Season". United States Centers for Disease Control and Prevention. Retrieved 2026-08-10.
- ↑ 5.0 5.1 5.2 Ferdinands JM, Blanton LH, Alyanak E; et al. (2024). "Protection Against Influenza Hospitalizations From Enhanced Influenza Vaccines Among Older Adults: A Systematic Review and Network Meta-Analysis". Journal of the American Geriatrics Society. 72 (12): 3875–3889. doi:10.1111/jgs.19176.
- ↑ Skaarup KG, Lassen MCH, Hosseini K; et al. (2026). "High-Dose vs Standard-Dose Influenza Vaccines in Older Adults". JAMA. doi:10.1001/jama.2026.14620.
- ↑ 7.0 7.1 Hsiao A, Leong T, Fireman B; et al. (2026). "Adjuvanted vs High-Dose Influenza Vaccines in Older US Adults: A Cluster Randomized Crossover Study". JAMA Network Open. 9 (5): e2610120. doi:10.1001/jamanetworkopen.2026.10120.
- ↑ 8.0 8.1 Maloney P, Reeves EL, Wielgosz K; et al. (2026). "Interim Estimates of 2025-26 Seasonal Influenza Vaccine Effectiveness - United States, September 2025-February 2026". MMWR. Morbidity and Mortality Weekly Report. 75 (9): 116–123. doi:10.15585/mmwr.mm7509a2.
- ↑ 9.0 9.1 9.2 9.3 9.4 9.5 9.6 Committee on Infectious Diseases, American Academy of Pediatrics (2025). "Recommendations for Prevention and Control of Influenza in Children, 2025-2026". Pediatrics.
- ↑ 10.0 10.1 Zhao Y; et al. (2024). "Antiviral post-exposure prophylaxis for influenza: a systematic review and network meta-analysis". Lancet. doi:10.1016/S0140-6736(24)01345-2.
- ↑ 11.0 11.1 11.2 11.3 "FDA Orange Book". U.S. Food and Drug Administration. Retrieved 2026-08-10.
- ↑ Imran M, Puig-Barbera J, Ortiz JR; et al. (2024). "Relative Effectiveness of the MF59®-Adjuvanted Influenza Vaccine Versus High-Dose and Non-Adjuvanted Influenza Vaccines in Preventing Cardiorespiratory Hospitalizations During the 2019–2020 US Influenza Season". Influenza and Other Respiratory Viruses. 18 (4): e13288. doi:10.1111/irv.13288.