Influenza vaccine

Kathryn Dzintars, Pharm.D. BCPS
Pediatric Dosing Author: Bethany Sharpless Chalk, Pharm.D., BCPPS

VACCINE TYPE

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

  • Inactivated influenza vaccine, Quadrivalent (IIV4)
    • Available as high-dose vaccination
  • Recombinant influenza vaccine, Quadrivalent (RIV4)
  • Live attenuated influenza vaccine, Quadrivalent (LAIV4)

INDICATIONS

ACIP RECOMMENDATIONS

  • Universal vaccination is recommended to all people aged 6 months and older who are otherwise without contraindications to vaccination.
    • Do not delay a specific vaccine preparation if an appropriate vaccine is unavailable.
    • Note: for the 2023-2024 season, the CDC recommends either the inactivated influenza vaccine (IIV), recombinant influenza vaccine (RIV) or the LAIV (intranasal).
      • For the 2023-2024 influenza season, inactivated influenza vaccines (IIVs) will be available in the quadrivalent (IIV4) formulation only, including the high-dose (HD) vaccine. The recombinant influenza vaccine (RIV) will also be available in a quadrivalent formulation (RIV4). LAIV4 is again an option for those considered appropriate. Trivalent vaccines are no longer being offered.
        • Vaccine virus strains included in 2023–2024 U.S. formulations: updates to the influenza A(H1N1)pdm09-like virus
          • U.S. egg-based influenza vaccines: A/Victoria/4897/2022(H1N1)pdm09-like virus, A/Darwin/9/2021 (H3N2)-like a virus, B/Austria/1359417/2021-like (Victoria lineage) virus, and B/Phuket/3073/2013 (Yamagata-lineage)-like virus.
          • U.S. cell culture-based vaccine (ccIIV4) and recombinant (RIV4) influenza vaccines: A/Wisconsin/67/2022 (H1N1)pdm09-like virus, A/Darwin/6/2021 (H3N2)-like virus, B/Austria/1359417/2021 (Victoria lineage)-like virus, B/Phuket/3073/2013 (Yamagata lineage)-like virus.
  • For persons with a history of egg allergy:
    • All persons > 6 months of age with an egg allergy should receive an influenza vaccine with any otherwise appropriate vaccine for the recipient’s age and health status. It is no longer recommended that persons with an egg allergy with symptoms other than urticaria (e.g., angioedema, anaphylaxis) be vaccinated in a monitored space. Egg allergy alone necessitates no additional safety measures for influenza vaccine beyond those recommended for any vaccine recipient, regardless of the severity of the previous reaction to egg.
    • See the influenza immunization and prophylaxis module for more details.
  • ACIP recommends that all adults over the age of 65 years receive any one of the HIGH-DOSE or adjuvanted influenza vaccines: HD-IIV4, RIV4 or aIIV4.

OTHER INFORMATION

  • Inactivated influenza vaccine can be used for anyone 6 months and older.
  • For the 2023-2024 influenza season, vaccination providers may choose to administer LAIV4 as an option for whom it is appropriate.
  • Flu vaccination in the era of COVID-19
    • Influenza vaccination to individuals > 6 months of age to reduce the prevalence of influenza may reduce symptoms that might be confused with COVID-19, and increased influenza vaccination may mitigate the severity of influenza illness, reduce hospitalizations and reduce intensive care unit admissions.
    • For those who have acute illness with suspected or laboratory-confirmed COVID-19 disease, consider delaying influenza vaccination until acute illness has resolved.
    • Guidance is available at https://www.cdc.gov/vaccines/pandemic-guidance/index.html

FORMS

brand name

preparation

manufacturer

route

form

dosage^

cost*

Afluria (6 months - 35 months)

Inactivated quadrivalent influenza vaccine Influenza

Seqiris

IM

Syringe

Vial

(10 doses)

0.25 mL

$20.79

$19.22

Afluria ( > 36 months)

Inactivated quadrivalent influenza vaccine Influenza

Seqirus

IM

Syringe

(* > 18y jet injector)

Vial

(10 doses)

0.5 mL

$20.79

$19.22

Fluarix Quadrivalent (> 6 months)

Inactivated Quadrivalent influenza vaccine, ccIIV4

GSK

IM

Syringe

0.5 mL

$19.73

FluBlok (> 18 years). Non-Egg Based.

Recombinant quadrivalent influenza vaccine, RIV4

Sanofi

IM

Vial (10 doses)

0.5 mL

$64.51

Flucelvax (>2 years)

Inactivated quadrivalent influenza vaccine

(preservative-free, antibiotic-free)

Seqirus

IM

Syringe

0.5 mL

$30.10

Flulaval Quadrivalent (>6 months)

Inactivated Quadrivalent influenza vaccine

GlaxoSmithKline

IM

Vial (10 doses)

0.5 mL

$19.73

FluMist Quadrivalent (2-49 years)

Live attenuated influenza vaccine

Astra Zeneca

Intranasal

Intranasal sprayer

0.2 mL

$24.50

Fluzone ( >6 months)

Inactivated quadrivalent vaccine

Sanofi-Pasteur

IM

Syringe

0.5 mL

$18.43

Fluzone High Dose (for persons ≥ 65 years)

Inactivated

quadrivalent influenza vaccine

Sanofi-Pasteur

IM

Syringe

0.7 mL

$61.48

Fluad (> 65 years)

Adjuvanted inactivated quadrivalent influenza vaccine

Seqirus

IM

Syringe

0.5 mL

$64.51

*Prices represent the specified cost per unit and the "Average Wholesale Price" (AWP).
^Dosage is indicated in mg unless otherwise noted.

PATHOGEN DIRECTED PROTECTION

  • Influenza A and B
  • 2023 - 2024 season: recomposed strains compared to the 2022-2023 season.
    • U.S. egg-based influenza vaccines: A/Victoria/4897/2022(H1N1)pdm09-like virus, A/Darwin/9/2021 (H3N2)-like virus, B/Austria/1359417/2021-like (Victoria lineage) virus, and B/Phuket/3073/2013 (Yamagata-lineage)-like virus.
    • U.S. cell culture-based vaccine (ccIIV4) and recombinant (RIV4) influenza vaccines: A/Wisconsin/67/2022 (H1N1)pdm09-like virus, A/Darwin/6/2021 (H3N2)-like virus, B/Austria/1359417/2021 (Victoria lineage)-like virus, B/Phuket/3073/2013 (Yamagata lineage)-like virus.
  • No preferential recommendation is made for one influenza vaccine over another (including children, 2023-2024 season).
  • Approximately 10 - 14 days are required to acquire immunologic protection.
    • Seroconversion in 76% and 66% of adults ages 18-49 and 50-64, respectively.
    • Titers ≥ 1:40 was achieved in 100% and 94% of adults ages 18-49 and 50-64, respectively.

DOSE/ADMINISTRATION

Adult PRIMARY SERIES

  • Should be given before the onset of influenza in the community; vaccines are usually available by mid- to late-August. The preference is to vaccinate by the end of October.
  • For adults living with HIV
    • Annual seasonal influenza vaccination is indicated for all people with HIV per the general vaccination series. Do not use the live attenuated (Flumist) when the CD4 count is < 200 cells/mm3.

Pediatric and Adult Vaccines

Age Indication

Dosage

Afluria

Quadrivalent

6 - 35 months

> 36 months

0.25 mL IM

0.5 mL IM

Fluarix Quadrivalent

≥ 6 months

0.5 mL IM

Flucelvax Quadrivalent

≥ 2 years

0.5 mL IM

Flulaval Quadrivalent

≥ 6 months

0.5 mL IM

FluMist Quadrivalent

≥ 2 - 49 years

0.2 mL IN

(0.1 mL per nostril)

Fluzone Quadrivalent

> 6 months

0.5 mL IM

ADULT VACCINES ONLY

FluBlok Quadrivalent

> 18 years

0.5 mL IM

Fluzone HIGH DOSE quadrivalent

> 65 years

0.7 mL IM

Fluad Adjuvant Quadrivalent

> 65 years

0.5 mL IM

Adult BOOSTER

  • Required each season due to reformulation based on recently circulating influenza strains.

Pediatric PRIMARY SERIES

Should be given before the onset of influenza in the community; vaccines are usually available by mid- to late-August. The preference is to vaccinate by the end of October.

Children: ages 6 months - 8 years, preferably before the start of the influenza season. See table.

  • Administer 2 doses ≥ 4 weeks apart if any of the following:
    • Patient’s first season of influenza immunization
    • The patient received ≤ 1 dose of quadrivalent influenza vaccine before July 1, preceding the current influenza season.
    • If vaccination history is unknown
  • Ages 2-8 years: no preference for any vaccine for healthy children without contraindications
  • See table for age and vaccine-specific dosing.

Pediatric BOOSTER

  • Required each season due to reformulation based on recently circulating influenza strains.

ADVERSE DRUG REACTIONS

GENERAL

  • Intranasal LAIV vaccine is not recommended in children < 24 months of age because of the increased risk of hospitalization and wheezing.

COMMON

  • IIV:
    • Soreness at the injection site, usually > 2 days in ~30%
    • Injection site reaction (mild transient) was reported in 36% of pts receiving Fluzone High-Dose (compared to 24% with standard Fluzone).
  • LAIV: runny nose/nasal congestion; headache, cough, and sore throat incidence were comparable to placebo.

OCCASIONAL

  • IIV: fever and malaise: 1.1% reported moderate to severe fevers with Fluzone High-Dose (compared to 0.3% with standard Fluzone).
  • LAIV: wheezing (especially in children 6-11 months). Avoid Flumist in children aged < 5 years with possible reactive airway disease (e.g., recurrent wheezing or a recent wheezing episode).

RARE

  • ALL:
    • Guillain-Barré syndrome: estimate 8 excess cases of GBS per 1 million vaccinations. This rate from the pandemic vaccine is similar to that found in seasonal influenza vaccines.
    • Allergy: hives, angioedema, asthma.
    • Ocular and respiratory symptoms: red eyes, cough, wheeze, chest tightness, difficulty breathing, facial swelling, and sore throat (associated with a formulation available in Canada during the 2000-2001 season).
  • IIV: febrile seizure reported in 5-9 cases/1,000 vaccinated children < 5 yrs old, with most seizures occurring < 3 yrs old when children received IIV (CSL Biotherapies) in Australia.

VACCINE/DRUG INTERACTIONS

  • Immunosuppressive therapies (corticosteroids, alkylating drugs, antimetabolites, and radiation): do not co-administer LAIV. May theoretically increase the risk of disseminated infection.
  • Can be co-administered with the pneumococcal vaccine, as well as the COVID vaccinations (Pfizer BioNTech, Moderna, J&J)
  • Reports of the influenza vaccine inhibiting the clearance of warfarin, theophylline, and phenytoin, although controlled studies have shown inconsistent results.
  • The attenuated intranasal influenza vaccine should not be administered until 48 hours after cessation of antiviral compounds. Antiviral drugs should not be administered until 2 weeks after administering the live attenuated intranasal influenza vaccine.

CONTRAINDICATIONS

  • Egg allergy is no longer a contraindication to receipt of the influenza vaccine. It is no longer recommended that persons with an egg allergy with symptoms other than urticaria (e.g., angioedema, anaphylaxis) be vaccinated in a monitored space. Egg allergy alone necessitates no additional safety measures for influenza vaccine beyond those recommended for any vaccine recipient, regardless of the severity of the previous reaction to egg.
  • LAIV: a history of hypersensitivity to vaccine components, children and adolescents (5-17 years of age) receiving aspirin, individuals with a history of Guillain-Barré syndrome, and individuals with immune deficiency diseases.
    • Children aged 6 to 12 months may have a higher rate of wheezing and hospitalization with LAIV.

IMMUNE RESPONSE

  • 6 months-8yrs: 86% had antibody response with 2 doses, but only 27% with 1 dose.
    • ACIP emphasizes the importance of administering 2 doses of vaccine to all children aged 6 months to 8 years if they have not been vaccinated previously at any time with either live, attenuated influenza vaccine.
      • LAIV: doses separated by >6 weeks.
      • IIV: doses separated by >4 weeks.
  • Adults >65 years: Fluzone High-Dose elicited significantly higher hemagglutination inhibition (HI) titers against all three influenza virus strains. The clinical effectiveness of the High-Dose Fluzone vaccine compared to the standard Fluzone vaccine appears more efficacious; however, no preferential recommendation (yet) is made for high-dose Fluzone over standard-dose IIV.

CLINICAL EFFICACY

  • Vaccine efficacy depends on the match of epidemic and vaccine strains; it has been consistently well-matched over the last decade. Prevention efficacy:
    • Young adults or healthy elderly: ~70%.
    • Elderly in nursing homes: 30-40%, but reduces influenza mortality by 80%.
    • Vaccine efficacy may be decreased in the elderly and immunosuppression.
    • High-dose vaccine (age > 65 yrs): relative efficacy, 24.2% compared to SIV, suggesting enhanced protection with HD vaccine.
  • In adults, intranasally administered live attenuated vaccine resulted in a 40.9% reduction in febrile upper respiratory tract illnesses during a season with a poor match of epidemic and vaccine influenza strains.

OTHER INFORMATION

  • Estimated vaccination coverage remains < 50% among all patients for whom routine annual vaccination is recommended, including young children and adults with risk factors for influenza complications, healthcare personnel (HCP), and pregnant women.
  • Influenza is a major infectious cause of death in the U.S. (3,000 to 80,000 annually); most are elderly, in nursing homes, or have chronic diseases.
  • Providing the vaccine to healthy adults generally reduces URIs and employee absenteeism, but conflicting data on cost-effectiveness.
  • Healthcare workers should be vaccinated to protect patients and other healthcare workers; they must avoid high-risk pt contact if given FluMist x 7d post-administration.
  • LAIV is shipped refrigerated and should be kept refrigerated (35-46°F).
  • Children with reactive airway disease, persons with underlying medical conditions with a higher risk for influenza complications, children aged 6-23 months, and persons aged >49 years should not receive LAIV.
  • Serious flu-related complications have been reported in obese patients and post-partum women.
  • Flu vaccination in the era of COVID-19
    • Influenza vaccination to individuals > 6 months of age to reduce the prevalence of influenza may reduce symptoms that might be confused with COVID-19, and increased influenza vaccination may mitigate the severity of influenza illness, reduce hospitalizations and reduce intensive care unit admissions.
    • For those who have acute illness with suspected or laboratory-confirmed COVID-19 disease, consider delaying influenza vaccination until the acute illness has resolved.
    • Guidance is available at https://www.cdc.gov/vaccines/pandemic-guidance/index.html

References

  1. COMMITTEE ON INFECTIOUS DISEASES. Recommendations for Prevention and Control of Influenza in Children, 2023-2024. Pediatrics. 2023.  [PMID:37641884]

    Comment: American Academy of Pediatrics recommendations for 2023-2024.

  2. Grohskopf LA, Blanton LH, Ferdinands JM, Chung JR, Broder KR, Talbot HK. Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices — United States, 2023–24 Influenza Season. MMWR Recomm Rep 2023;72(No. RR-2):1–25. DOI: http://dx.doi.org/10.15585/mmwr.rr7202a1

    Comment:
    Annual recommendations from the Advisory Committee on Immunization Practices for the 2023-34 influenza season. Changes to the guidance are minimal but significant. While there is only a single change to the 4 components of the quadrivalent vaccines, the committee has significantly eased caution against administration to those with egg allergies. Regardless of the reaction, Egg allergy alone necessitates no additional safety measures for influenza activation beyond those recommended for any vaccine recipient.


Last updated: November 7, 2023