Influenza vaccine

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

VACCINE TYPE

Four major types available in the U.S.:

  • Inactivated influenza vaccine, Trivalent (IIV3)
  • 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 recommended to all people aged 6 months and older who are otherwise without contraindications to vaccination.
    • Do not delay for a specific vaccine preparation if an appropriate vaccine is otherwise available.
    • Note: for the 2020-2021 season, CDC recommends either the inactivated influenza vaccine (IIV), recombinant influenza vaccine (RIV) or the LAIV (intranasal).
      • For the 2020-2021 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). The adjuvanted inactivated influenza vaccine (aIIV3) will be the only available trivalent formulation. LAIV4 is again an option for those considered appropriate.
        • Vaccine virus strains included in 2020–2021 U.S. formulations: recomposed strains compared to the 2019-2020 season.
          • U.S. egg-based influenza vaccines: A/Guangdong-Maonan/SWL1536/2019(H1N1)pdm09-like virus, A/Hong Kong/2671/2019 (H3N2)-like virus, B/Washington/02/2019-like (Victoria lineage) virus, and B/Phuket/3073/2013 (Yamagata-lineage)-like virus.
            • The MF59-adjuvanted IIV (aIIV) will also be available as a trivalent vaccine and does not include the B/Phuket/3073/2013 (Yamagata-lineage)-like virus.
          • U.S. cell culture-based vaccine (ccIIV4) and recombinant (RIV4) influenza vaccines: A/Hawaii/70/2019 (H1N1)pdm09-like virus, A/Hong Kong/45/2019 (H3N2)-like virus, B/Washington/02/2019 (Victoria lineage)-like virus, B/Phuket/3073/2013 (Yamagata lineage)-like virus.
  • For persons with a history of egg allergy:
    • History of egg allergy who have experienced only urticaria (hives) after exposure to eggs may receive any licensed, recommended, and age-appropriate influenza vaccine (IIV, RIV4, or LAIV4).
    • History of egg allergy who have had reactions to eggs other than urticaria (e.g. angioedema, respiratory distress, recurrent vomiting) or who required epinephrine or other emergency medical intervention may also receive any IIV, RIV4 or LAIV4 vaccine. If a vaccine other than ccIIV4 or RIV4 is used, the vaccine should be administered in a medical setting and supervised by a health care provider able to manage any reactions.
    • See influenza immunization and prophylaxis module for more details.

OTHER INFORMATION

  • Inactivated influenza vaccine can be used for any persons aged 6 months and older.
  • For the 2020-2021 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 dose)

Also jet injector

0.25 mL

$16.65

Afluria ( > 36 months)

Inactivated quadrivalent influenza vaccine Influenza

Seqirus

IM

Syringe

Vial (10dose)

Also jet injector

0.5 mL

$16.65

Fluarix Quadrivalent (> 6 months)

Inactivated Quadrivalent influenza vaccine, ccIIV4

GSK

IM

Syringe

0.5 mL

$17.30

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

Recombinant quadrivalent influenza vaccine, RIV4

Sanofi

IM

Vial (10 dose)

0.5 mL

$53.61

Flucelvax (>4 years)

Inactivated quadrivalent influenza vaccine

(preservative-free, antibiotic-free)

Seqirus

IM

Syringe

0.5 mL

$20.32

Flulaval Quadrivalent (>6 months)

Inactivated Quadrivalent influenza vaccine

ID Biomedical Corp. of Quebec

IM

Vial (10 dose)

0.5 mL

$17.30

FluMist Quadrivalent (2-49 years)

Live attenuated influenza vaccine

Astra Zeneca

Intranasal

Intranasal sprayer

0.2 mL

$23.70

Fluzone ( >6 months)

Inactivated quadrivalent vaccine

Sanofi-Pasteur

IM

Syringe

0.5 mL

$17.04

Fluzone High Dose (for persons ≥ 65 years)

Inactivated trivalent influenza vaccine

Sanofi-Pasteur

IM

Syringe

0.5 mL

$53.61

Fluad (> 65 years)

Adjuvanted inactivated trivalent influenza vaccine

Seqirus

IM

Syringe

0.5 mL

$47.25

Fluad (> 65 years)

Adjuvanted inactivated quadrivalent influenza vaccine

Seqirus

IM

Syringe

0.5 mL

$49.25

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

PATHOGEN DIRECTED PROTECTION

  • Influenza A and B
  • 2020 - 2021 season: recomposed strains compared to the 2019-2020 season.
    • U.S. egg-based influenza vaccines: A/Guangdong-Maonan/SWL1536/2019(H1N1)pdm09-like virus, A/Hong Kong/2671/2019 (H3N2)-like virus, B/Washington/02/2019-like (Victoria lineage) virus, and B/Phuket/3073/2013 (Yamagata-lineage)-like virus.
      • The MF59-adjuvanted IIV (aIIV) will also be available as a trivalent vaccine and does not include the B/Phuket/3073/2013 (Yamagata-lineage)-like virus.
    • U.S. cell culture-based vaccine (ccIIV4) and recombinant (RIV4) influenza vaccines: A/Hawaii/70/2019 (H1N1)pdm09-like virus, A/Hong Kong/45/2019 (H3N2)-like virus, B/Washington/02/2019 (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, 2020-2021 season).
  • Approximately 10 - 14 days required to acquire immunologic protection.
    • Seroconversion in 76% and 66% in 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 prior to the onset of influenza in the community; vaccines usually available middle to the end of August. 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 < 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

≥ 4 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

0.5 mL IM

Fluad Adjuvant Trivalent

> 65 years

0.5 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 prior to the onset of influenza in the community; vaccines usually available middle to the end of August. Preference is to vaccinate by the end of October.

Children: for ages 6 months - 8 years, preferably prior to 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 trivalent or quadrivalent influenza vaccine prior to 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 increased risk of hospitalization and wheezing.

COMMON

  • IIV:
    • Soreness at the injection site, usually > 2 days in ~30%
    • Injection site reaction (mild transient) reported in 36% of pts receiving Fluzone High-Dose (compared to 24% with standard Fluzone).
  • LAIV: runny nose/nasal congestion; the incidence of headache, cough, and sore throat 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 airways 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 use of 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 risk of disseminated infection.
  • Can be co-administered with the pneumococcal vaccine.
  • Reports of the influenza vaccine inhibiting the clearance of warfarin, theophylline, phenytoin, although controlled studies have shown inconsistent results.
  • 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 the administration of live attenuated intranasal influenza vaccine.

CONTRAINDICATIONS

  • IIV: allergy to eggs or prior severe allergic reaction, or fever > 40°C. No contraindication if only prior local reaction.
    • Note: if an "egg-allergic" individual can normally eat baked goods, this means egg allergy is unlikely to be significant regarding receipt of the influenza vaccine.
  • LAIV: a history of hypersensitivity to vaccine components, including eggs or egg products, children and adolescents (5-17 years of age) receiving aspirin, individuals who have a history of Guillain-Barre 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--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 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; 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, health-care 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 appears to generally reduce URIs and employee absenteeism; conflicting data on cost-effectiveness.
  • Health care workers should be vaccinated to protect patients and other health care workers; 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 airways disease, persons with underlying medical conditions with 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 acute illness has resolved.
    • Guidance is available at https://www.cdc.gov/vaccines/pandemic-guidance/index.html

Basis for recommendation

  1. Grohskopf LA, Alyanak E, Broder KR, et al. Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices - United States, 2020-21 Influenza Season. MMWR Recomm Rep. 2020;69(8):1-24.  [PMID:32820746]

    Comment: The ACIP recommendations for the 2020-21 influenza season. Notable updates include changes to the vaccine composition from 2019-20, as well as discussion on the addition of two new influenza vaccines (Fluzone high dose quadrivalent, Fluad Quadrivalent). Vaccine composition is different between the egg-based vaccines and the cell culture-based vaccines. Finally, a discussion is provided on the possible impact of COVID-19 on the upcoming influenza season.

References

  1. COMMITTEE ON INFECTIOUS DISEASES. Recommendations for Prevention and Control of Influenza in Children, 2019-2020. Pediatrics. 2019;144(4).  [PMID:31477606]

    Comment: Recs for peds.

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Last updated: October 27, 2020