VACCINE TYPE

Four major types are available in the U.S.:

• Inactivated influenza vaccine, Trivalent (IIV3)
  • Available as a high-dose vaccine.
• Recombinant influenza vaccine, Trivalent (RIV3)
• Live attenuated influenza vaccine, Trivalent (LAIV3)
• mRNA influenza vaccine, Trivalent
  • FDA-approved August 2026; not yet incorporated into CDC’s September 2026 interim influenza vaccine guidance.
• All 2026-27 Influenza season vaccines will be trivalent vaccines, as the influenza B/Yamagata lineage is no longer circulating.

INDICATIONS

FORMS

^†FluMist is now available for self-administration for recipients aged 18 - 49 years or administration by a caregiver ≥ 18 years of age for those aged 2 - 17 years.

*Prices represent the specified cost per unit and the "Average Wholesale Price" (AWP).

**Multidose presentation contains thimerosal and is not consistent with current ACIP preference for single-dose, preservative-free formulations.
^Dosage is indicated in mg unless otherwise noted.

PATHOGEN DIRECTED PROTECTION

• Influenza A and B
• No influenza vaccine is preferentially recommended when more than one age-appropriate vaccine is available, except in adults ≥65 years, for whom HD-IIV3, RIV3, or aIIV3 are preferred.
• Approximately 2 weeks are required for development of vaccine-induced protection.

DOSE/ADMINISTRATION

ADVERSE DRUG REACTIONS

VACCINE/DRUG INTERACTIONS

• Immunosuppressive therapies (corticosteroids, alkylating drugs, antimetabolites, and radiation): Do not co-administer LAIV. This may theoretically increase the risk of disseminated infection.
• It can be co-administered with the pneumococcal vaccine and the COVID vaccinations (Comirnaty, Spikevax, Novavax). In infants and children < 24 months, IIV can be co-administered with nirsevimab (Beyfortus) if indicated.
• The attenuated intranasal influenza vaccine should not be administered from 48 hours before through 2 weeks after LAIV; peramivir 5 days before through 2 weeks after; baloxavir 17 days before through 2 weeks after.
  • If antivirals are given in these windows, CDC advises revaccination with age-appropriate IIV3 or RIV3.

WARNINGS/CONTRAINDICATIONS

• Egg allergy:
  • Not a contraindication to influenza vaccination.
    • Persons aged ≥6 months with egg allergy may receive any age- and health-appropriate influenza vaccine, including egg-based products, regardless of the severity of a previous reaction to egg. No additional observation or other special safety measures are required beyond those recommended for any vaccine recipient.
    • A previous severe allergic reaction (e.g., anaphylaxis) to an influenza vaccine or to a vaccine component other than egg protein may be a contraindication or precaution, depending on the vaccine involved.
  • LAIV (FluMist) contraindications: Do not administer to:
    • Children and adolescents receiving aspirin- or salicylate-containing therapy.
    • Children aged 2–4 years with asthma or wheezing during the preceding 12 months.
    • Persons who are immunocompromised, including those with HIV infection, medication-associated immunosuppression, congenital or acquired immunodeficiency, or anatomic/functional asplenia.
    • Pregnant persons.
    • Close contacts/caregivers of severely immunocompromised persons who require a protected environment.
    • Persons with an active cranial CSF leak or a cochlear implant.
    • Persons with sufficiently recent receipt of an influenza antiviral that could interfere with LAIV replication (see Vaccine/Drug Interactions).
  • Precautions:
    • Guillain-Barré syndrome within 6 weeks of a previous influenza vaccine is a precaution—not an absolute contraindication—relevant to all influenza vaccines.
    • Moderate or severe acute illness, with or without fever, is a precaution to vaccination.
    • For LAIV, asthma in persons aged ≥5 years and other underlying conditions that increase the risk of complications from influenza are precautions; an age-appropriate inactivated or recombinant vaccine is generally preferred.

IMMUNE RESPONSE

• In adults aged ≥65 years, high-dose IIV (HD-IIV3), recombinant (RIV3), and MF59-adjuvanted IIV (aIIV3) generally produce enhanced immune responses and/or clinical protection compared with standard-dose unadjuvanted IIV. These three vaccines are preferentially recommended for this age group, although existing evidence is insufficient to consistently find one superior.
  
  • High-dose IIV (Fluzone High-Dose):
    • Contains approximately 4-fold more hemagglutinin antigen per strain than standard-dose IIV and produces higher HAI antibody titers and seroprotection rates in older adults.
    • In a large randomized trial of adults ≥65 years, HD-IIV reduced laboratory-confirmed influenza by 24.2% relative to standard-dose IIV (95% CI, 9.7%–36.5%).[10]
    • More recent randomized data also support improved protection against severe outcomes: among adults aged 65–79 years, HD-IIV had 23.7% relative effectiveness against hospitalization for influenza or pneumonia and 31.8% against influenza hospitalization compared with standard-dose vaccine.[5]
  • MF59-adjuvanted IIV (Fluad):
    • MF59 enhances innate immune activation and can increase the magnitude and breadth of antibody responses, including responses to antigenically divergent influenza strains. Enhanced cellular responses have also been demonstrated.
    • Clinical effectiveness compared with standard-dose IIV has generally favored aIIV in observational studies, although estimates vary substantially by season.[6]
    • Direct comparative evidence does not demonstrate consistent superiority over HD-IIV. In a large 2023–2024 pragmatic randomized comparison in adults ≥65 years, effectiveness against PCR-confirmed influenza was similar for aIIV and HD-IIV (relative VE of aIIV vs HD-IIV, 1.5%; 95% CI, −8.4% to 10.5%).[4]
  • Recombinant influenza vaccine (FluBlok):
    • Contains 3-fold more hemagglutinin antigen per strain than standard-dose IIV and is produced without eggs, avoiding egg-adaptive antigenic changes.
    • In a randomized trial of adults ≥50 years during an H3N2-predominant, antigenically mismatched season, RIV reduced RT-PCR-confirmed influenza-like illness by 30% relative to standard-dose IIV (95% CI, 10%–47%); benefit was not statistically established in the ≥65-year subgroup alone.[9]
    • A subsequent large pragmatic study in adults aged 50–64 years found 15.3% relative effectiveness against PCR-confirmed influenza compared with standard-dose influenza vaccines.[7]
  • mRNA influenza vaccine (MFLUSIVA)[12]:
    • In adults ≥65 years, the Moderna mRNA influenza vaccine used to support licensure produced higher day-29 HAI geometric mean titers and seroconversion rates than Fluzone High-Dose for all vaccine strains, meeting prespecified immunogenicity superiority criteria.
    • In adults ≥50 years, MFLUSIVA demonstrated 26.6% relative vaccine efficacy (95% CI, 16.7%–35.4%) versus standard-dose IIV against RT-PCR-confirmed influenza-like illness; relative efficacy was 26.1% among those aged 50–64 years.
    • For adults ≥65 years, approval was based primarily on the superior immunogenicity comparison with high-dose IIV; supportive clinical efficacy versus standard-dose IIV was 27.4%, but confirmatory clinical-effectiveness data versus high-dose vaccine are required under the accelerated approval pathway.
  • Live attenuated influenza vaccine (LAIV; FluMist):
    • LAIV replicates locally in the nasopharynx and generates a qualitatively different immune response from injected vaccines, including mucosal IgA, systemic antibody, and cellular immune responses.
    • Serum HAI responses after LAIV are often lower than after IIV and are a poor correlate of LAIV-mediated protection; mucosal and cellular immunity appear to contribute importantly to protection.[3]
    • Historical randomized trials demonstrated superior efficacy of LAIV versus IIV in some pediatric populations, but effectiveness has varied by season and vaccine strain.[11] Recent data support effectiveness in children, but there is no current recommendation to preferentially use LAIV over other age-appropriate influenza vaccines.

CLINICAL EFFICACY

• Vaccine efficacy varies substantially by season, circulating strain, age, and host factors; enhanced vaccines are preferentially recommended for ≥65.

OTHER INFORMATION

• mRNA Influenza vaccine approved by FDA August 5, 2026, for prevention of influenza caused by vaccine-matched influenza A and B viruses in persons ≥50 years of age.
  • Approval in adults 50–64 years was through the traditional approval pathway based on clinical efficacy data compared to standard-dose IIV for RT-PCR-confirmed infection; the indication in adults ≥65 years was granted under accelerated approval based primarily on immunogenicity data, with continued approval contingent on confirmation of clinical benefit.
    • MFLUSIVA (FDA label) had 26.6% relative vaccine efficacy (95% CI, 16.7%-35.4%) versus standard-dose IIV for RT-PCR-confirmed influenza-like illness. The 50-64 subgroup rVE was 26.1% (95% CI, 12.3%-37.7%). In ≥65-year-olds, the supportive clinical efficacy estimate versus standard-dose IIV was 27.4% (95% CI, 12.1%-40.0%), while the accelerated approval was principally supported by superior HAI immunogenicity versus Fluzone High-Dose.
      • For the ≥75 subgroup, the descriptive rVE was 25.3%, but its CI crossed zero (−10.4 to 49.5); this is why the FDA approval for the ≥65 indication rests principally on immunogenicity rather than efficacy.
• Providing the vaccine to healthy adults generally reduces URIs and employee absenteeism, but there is conflicting data on cost-effectiveness.
• Healthcare workers should be vaccinated to protect patients and other healthcare workers.
  • If given FluMist within 7 days post-administration, avoid contact for 7 days with severely immunosuppressed persons who require a protected environment.

Basis for recommendation

1. Grohskopf LA, Blanton LH, Ferdinands JM, et al. Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices - United States, 2025-26 Influenza Season. MMWR Morb Mortal Wkly Rep. 2025;74(32):500-507.  [PMID:40879559]

   Comment: Annual update from ACIP with recommendations for flu vaccination for the 2025-26 season. Notable updates include a substitution for the H3N2 component of the vaccine, expansion of approval for FluBlok to individuals 9 years of age and older (previously 18 years of age), and the recommendation that FluMist be available for self-administration. Additionally, all recipients should receive a vaccine that is free of thimerosal as a preservative.
   

2. American Academy of Pediatrics. Recommendations for Prevention and Control of Influenza in Children, 2026–2027: Policy Statement. accessed 10/27/2026.

   Comment: Annual recommendations from the Committee on Infectious Diseases of the American Academy of Pediatrics for the 2026-2027 season. All children six months and older are still recommended. The companion AAP technical report has greater detail and background.
   

References

3. Dvorscek AR, Kushnir AS, Dibben O, et al. Mucosal immunity as a vaccine-induced correlate of protection against influenza. Mucosal Immunol. 2026;19(4):100381.  [PMID:42419427]

   Comment: Industry-sponsored review of mucosal correlates of protection after influenza vaccination. Serum LAIV-derived HAI titers correlated poorly with LAIV-mediated protection, whereas nasal antibodies and mucosal B- and T-cell responses likely contribute importantly to immunity.
   

4. Hsiao A, Leong T, Fireman B, et al. Adjuvanted vs High-Dose Influenza Vaccines in Older US Adults: A Cluster Randomized Crossover Study. JAMA Netw Open. 2026;9(5):e2610120.  [PMID:42081247]

   Comment: Large cluster-randomized crossover study of 429,595 adults aged ≥65 years comparing MF59-adjuvanted vaccine with high-dose IIV during 2023–2024. No significant difference in PCR-confirmed influenza was demonstrated (rVE 1.5%; 95% CI, −8.4% to 10.5%); thus, it is not possible to say there is a preference between these two enhanced vaccines.
   

5. Pardo-Seco J, Rodríguez-Tenreiro-Sánchez C, Giné-Vázquez I, et al. High-Dose Influenza Vaccine to Reduce Hospitalizations. N Engl J Med. 2025;393(23):2303-2312.  [PMID:40888694]

   Comment: Large randomized GALFLU trial in community-dwelling adults aged 65–79 years across the 2023–2024 and 2024–2025 seasons. Compared with standard-dose IIV, high-dose IIV was associated with 23.7% relative effectiveness against hospitalization for influenza or pneumonia and 31.8% against influenza hospitalization. There was no significant difference in safety/SAEs between groups.
   

6. Askar M, Ali KA, Batke M, et al. Relative Efficacy, Effectiveness and Safety of Newer and/or Enhanced Seasonal Influenza Vaccines for the Prevention of Laboratory-Confirmed Influenza in Individuals Aged 18 years and Over: Update of a Systematic Review. Rev Med Virol. 2025;35(2):e70020.  [PMID:39994168]

   Comment: This study found that MF59-adjuvanted vaccine effectiveness generally favored enhanced vaccination, but had heterogeneous estimates and low certainty for laboratory-confirmed influenza.
   

7. Hsiao A, Yee A, Fireman B, et al. Recombinant or Standard-Dose Influenza Vaccine in Adults under 65 Years of Age. N Engl J Med. 2023;389(24):2245-2255.  [PMID:38091531]

   Comment: Large cluster-randomized observational study of >1.6 million adults aged 18–64 years comparing recombinant influenza vaccine with standard-dose egg-based influenza vaccines. Among adults aged 50–64 years, recombinant vaccine provided 15.3% greater relative effectiveness (95% CI, 5.9%–23.8%) against PCR-confirmed influenza; no significant advantage was demonstrated for influenza-related hospitalization.
   

8. Cowling BJ, Perera RAPM, Valkenburg SA, et al. Comparative Immunogenicity of Several Enhanced Influenza Vaccine Options for Older Adults: A Randomized, Controlled Trial. Clin Infect Dis. 2020;71(7):1704-1714.  [PMID:31828291]

   Comment: Randomized comparative immunogenicity study in adults aged 65–82 years evaluating standard-dose IIV versus MF59-adjuvanted, high-dose, and recombinant vaccines. Enhanced vaccines generally produced greater HAI and/or microneutralization responses than the standard-dose vaccine. Immunogenicity study. It did not assess comparative clinical efficacy.
   

9. Dunkle LM, Izikson R, Patriarca P, et al. Efficacy of Recombinant Influenza Vaccine in Adults 50 Years of Age or Older. N Engl J Med. 2017;376(25):2427-2436.  [PMID:28636855]

   Comment: Randomized trial in adults aged ≥50 years showing 30% greater relative efficacy of recombinant influenza vaccine versus standard-dose egg-based IIV against RT-PCR-confirmed influenza-like illness during an H3N2-predominant, antigenically mismatched season. The ≥65-year subgroup alone did not demonstrate statistically significant superiority.
   

10. DiazGranados CA, Dunning AJ, Kimmel M, et al. Efficacy of high-dose versus standard-dose influenza vaccine in older adults. N Engl J Med. 2014;371(7):635-45.  [PMID:25119609]

    Comment: Pivotal randomized efficacy trial in adults aged ≥65 years. High-dose IIV produced higher HAI antibody responses and provided 24.2% greater relative efficacy (95% CI, 9.7%–36.5%) than standard-dose IIV against laboratory-confirmed influenza. This was the first major study supporting preferential use of enhanced influenza vaccine in older adults.
    

11. Belshe RB, Edwards KM, Vesikari T, et al. Live attenuated versus inactivated influenza vaccine in infants and young children. N Engl J Med. 2007;356(7):685-96.  [PMID:17301299]

    Comment: Landmark randomized trial comparing LAIV with IIV in young children; LAIV resulted in approximately 55% fewer culture-confirmed influenza cases than IIV. Historical evidence of superior pediatric efficacy in that setting, but subsequent strain- and season-specific variability means LAIV is not currently preferred over other age-appropriate vaccines.
    

12. Moderna. MFLUSIVA- influenza vaccine, mrna injection, suspension [Aug 2026]

    Comment: FDA prescribing information for MFLUSIVA, the Moderna trivalent mRNA influenza vaccine approved August 5, 2026, for adults aged ≥50 years. The 50–64-year indication received traditional approval based principally on a Phase 3 randomized trial comparing MFLUSIVA with standard-dose IIV; relative vaccine efficacy against RT-PCR-confirmed influenza-like illness was 26.6% overall (2.0% vs 2.8%; 95% CI, 16.7%–35.4%) and 26.1% among adults aged 50–64 years. The ≥65-year indication received accelerated approval based primarily on immunogenicity versus high-dose IIV, supported by descriptive relative efficacy of 27.4% versus standard-dose IIV. Each 0.38-mL IM dose contains 37.5 mcg total mRNA (12.5 mcg encoding hemagglutinin from each of 3 influenza strains) in lipid nanoparticles; the product contains no egg protein, antibiotics, or preservatives. The label also provides age-stratified reactogenicity, storage/handling, contraindications, and the requirement for confirmatory evidence of clinical benefit in adults ≥65 years.
    
    
    
    

13. Interim Clinical Considerations for the Use of Seasonal Influenza Vaccines in the United States | Influenza (Flu) | CDC

    Comment:
    Per the CDC: "Because of legal uncertainties and inquiries, the CDC states the recommendations for seasonal influenza vaccination from the July 2025 immunization schedule remain in effect for the 2026-2027 influenza season.
    
    
    The above link references key take-home points for the 2026-2027 influenza season that are largely taken from the 2025-2026 MMWR report referenced in this module.
    Of note, the Afluria product is not available for the 2026-2027 season. MFLUSIVA, FDA-approved in August 2026, is not yet incorporated into this September 2026 interim CDC guidance.