Influenza, Vaccines

by Andrew Pavia, M.D. last updated Dec 04, 2023 11:28 AM © Antimicrobial Therapy, Inc.
influenza vaccine, Fluarix, Flublok, FluMist, FluAd

Indications for Vaccination


  • Annual influenza vaccination is indicated for everyone older than 6 months
  • Enhanced vaccines are recommended for those >65: High dose (HD-IIV4), adjuvanted (aIIV4) or recombinant (RIV4) are all considered enhanced vaccines
  • Children 6 months-8 years old should receive two doses as a primary series the first time they get flu vaccine. In subsequent years children receive one dose
  • Some people are at significantly higher risk of influenza complications. 
    • All children aged 6 through 59 months.
    • All persons aged ≥50 years.
    • Adults and children who have chronic pulmonary (including asthma), cardiovascular (excluding isolated hypertension), renal, hepatic, neurologic, hematologic, or metabolic disorders (including diabetes mellitus).
    • Persons who are immunocompromised due to any cause (including but not limited to immunosuppression caused by medications or HIV infection).
    • Persons who are or will be pregnant during the influenza season.
    • Children and adolescents (aged 6 months through 18 years) who are receiving aspirin- or salicylate-containing medications and who might be at risk for experiencing Reye syndrome after influenza virus infection.
    • Residents of nursing homes and other long-term care facilities.
    • American Indian or Alaska Native persons.
    • Persons who are extremely obese (body mass index ≥40 for adults).


  • In temperate regions, influenza in seasonal, typically October-May in the Northern hemisphere and April-September in the Southern Hemisphere
  • Vaccination is recommended in September through October, as well as throughout the influenza season if not already vaccinated.
  • Timing of influenza vaccine may be altered for those traveling to the Southern Hemisphere. Southern hemisphere vaccine formulation may be different and is usually not available in the north
  • Influenza  may circulate year round in tropical regions
  • Consider pre-departure vaccination for US residents at higher risk for complications traveling during the southern winter (April–September) to the Southern Hemisphere or to the tropics, or on a cruise ship or organized tourist group to any location if they were not vaccinated during the previous northern fall/winter.
  • All persons (regardless of risk status) who are vaccinated in preparation for travel before the upcoming influenza season’s vaccine is available should receive the current vaccine the following fall or winter.

Dose and Schedule

Vaccine (type, CDC acronym) Age Dose and Route Primary Schedule - routine Subsequent Booster
Standard dose inactivated egg-based          
Afluria Quadrivalent,

Standard dose, Egg-based, IIV4 ≥ 6 months

6 months-35 months 7.5 µg/0.25mL IM

≥ 3 years

15 µg/0.5 mL IM

2 doses initially if 6 months -8 years

Otherwise, single dose

Fluarix Quadrivalent,
FluLaval Quadrivalent,
Fluzone Quadivalent
Standard dose, Egg-based, IIV4 ≥ 6 months 15 µg/0.5 mL IM

2 doses initially if 6 months -8 years

Otherwise, single dose

Standard dose cell-based  

Flucelvax Quadrivalent Cell-based, Egg-free, ccIIV4 ≥ 6 months 15 µg/0.5 mL IM

2 doses initially if 6 months -8 years

Otherwise, single dose


Flublok Quadrivalent Recombinant, Egg-free, RIV4  ≥ 18 years 45 µg/0.5 mL IM Single dose Annual
Fluzone High-Dose Quadrivalent High dose, Egg-based, HD-IIV4 ≥ 65 years 60 µg/0.5 mL IM Single dose Annual
Fluad Quadrivalent Adjuvanted, Egg-based, aIIV4 ≥ 65 years 15 µg/0.5 mL IM Annual
Live attenuated  
FluMist Quadrivalent Attenuated live virus, Egg-based, LAIV4 2 years-49 years 106.5–7.5 fluorescent focus units/0.2 mL intranasal

2 doses initially if 6 months -8 years

Otherwise, single dose


Efficacy, Duration of Protection

Standard Vaccines

  • Efficacy varies by season; 0-60%. Average ~55% Clin Infect Dis 2023; 768: 540
  • Protection lasts around 6 months but wanes after ~4 months.
  • Waning at largely in those >60

Enhanced Vaccines

  • Clinical trial data are limited and not entirely consistent
  • Observational data are more available but subject to bias and unmeasured confounders
  • Generally studies have shown modest increased efficacy relative to standard vaccines in the range of 17-30% increase in relative efficacy
  • For more detail see CDC. Prevention and Control of Seasonal Influenza

Choice, Interchangeability

  • IIV4 products are largely interchangeable
  • LAIV4 has the narrowest age range of suitable patients
  • All 3 enhanced vaccines (aIIV4, HD-IIV4, RIV4) suitable for older adults. No adequate head to head comparisons


  • Allergic reactions to eating eggs, including anaphylaxis no longer need to be considered in the choice of influenza vaccines. As of 2023, ACIP recommends that all persons with egg allergy should receive an age appropriate influenza vaccine that is either egg-based or non-egg based. For a review of the evidence, see evidence to recommendation summary. 
  • All vaccines should be administered in a setting where anaphylaxis can be recognized and managed
  • History of anaphylaxis to any influenza vaccine is a contraindication to future use of all egg-based vaccines and LAIV
  • For LAIV, the following are considered contraindications:
    • Children who are receiving aspirin or salicylate containing medications
    • Children aged 2 through 4 years who have received a diagnosis of asthma or wheezing in the last 12 months
    • Children and adults who are immunocompromised due to any cause
    • Close contacts and caregivers of severely immunosuppressed persons who require a protected environment.
    • Pregnancy
    • Persons with active CSF leak or Persons with cochlear implants
    • Receipt of influenza antiviral medication within the previous 48 hours for oseltamivir and zanamivir, previous 5 days for peramivir, and previous 17 days for baloxavir


  • Moderate or severe acute illness with or without fever is a general precaution for vaccination
  • A history of Guillain-Barré syndrome (GBS) within 6 weeks of a previous dose of any type of influenza vaccine is considered a precaution
  • A history of a severe allergic reaction (e.g., anaphylaxis) to any egg-based IIV or LAIV of any valency is a precaution for the use of ccIIV4 or RIV4.
  • Fluzone, quadrivalent: syncope has been reported immediately following vaccination
    • Procedures should be in place to avoid injury from fainting.
  • For LAIV, Asthma in persons aged ≥5 years, moderate or severe current illness, and underlying conditions that increase the risk of influenza complications are precautions

History of egg allergy

  • Allergic reactions to eating eggs, including anaphylaxis, is no longer  factor. See above

Adverse Effects

  • Local reactions including pain, redness or swelling

Drug Interactions

  • Influenza antiviral medications impair the replication of LAIV leading to decreased efficancy

Special Populations

Pregnancy, Breastfeeding

  • Pregnancy is associated with an increased risk of complications from influenza and influenza vaccination is recommended during pregnancy
  • Influenza vaccination during pregnancy is associated with a decreased risk of respiratory illness and influenza during pregnancy and in the immediate post partum period
  • Influenza vaccination during pregnancy is associated with decreased risk of respiratory illness or influenza in neonates
  • Breastfeeding is not a contraindication or precaution

Immunocompromised / HIV

  • HIV is associated with decreased efficacy of influenza vaccines in patients with significant CD4 cell suppression
  • Other types of immunosuppression may decrease efficacy. For a complete discussion see Clin Infect Dis. 2014 Feb;58(3):e44
  • Immunocompromised patients should not receive LAIV4

Serologic Testing

  • Serologic testing has no role