Influenza vaccine

Kathryn Dzintars, Pharm.D. BCPS, Paul G. Auwaerter, M.D.

VACCINE TYPE

Four major types available in U.S.:

  • Inactivated influenza vaccine, Trivalent (IIV3)
    • Available at standard dose and high dose
  • Inactivated influenza vaccine, Quadrivalent (IIV4)
  • Recombinant influenza vaccine, Trivalent (RIV3)
  • Live attenuated influenza vaccine, Quadrivalent (LAIV4, intranasal preparation)

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 2018-2019 season, CDC recommends inactivated influenza vaccine (IIV) or recombinant influenza vaccine (RIV). LAIV (intranasal) is again recommended after a hiatus.
      • For 2018-19 influenza season, inactivated influenza vaccines (IIVs) will be available in both trivalent (IIV3) and quadrivalent (IIV4) formulations. Recombinant influenza vaccine (RIV) will be available in a trivalent formulation (RIV3). High-dose inactivated influenza vaccine (HD-IIV3) and adjuvanted inactivated influenza vaccine (aIIV3) will be available in trivalent formulations. LAIV4 is again an option for those considered appropriate.
        • Vaccine virus strains included in 2017–18 U.S. formulations: recomposed strains compared to 2016-17 season.
          • Trivalent vaccine: A/Michigan/45/2015 A(H1N1)pdm09-like virus, A/Singapore/INFIMH-16–0019/2016 A(H3N2)-like virus, and B/Colorado/06/2017-like (B/Victoria lineage) virus.
          • Quadrivalent vaccine: in addition to the above, quadrivalent vaccine includes an additional influenza B virus strain (B/Phuket/3073/2013–like virus).
  • For immediate protection: give antivirals (70-80% effective) + vaccine (2 weeks required for antibody response).
  • Egg allergy: with 2018-19 recommendations, history of egg allergy of any severity may receive any licensed, recommended, and age-appropriate influenza vaccine (IIV, RIV4, or LAIV4). IIV and RIV4 have been previously recommended. Only RIV4 is considered egg-free. 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 2018-2019 influenza season, vaccination providers may choose to administer LAIV4 as an option for whom it is appropriate (it was previously not recommended for the 2016-2017 and 2017-2018 influenza seasons due to concern for lack of effectiveness against influenza A).

FORMS

brand name

preparation

manufacturer

route

form

dosage^

cost*

Afluria (age >5 years)

Inactivated trivalent influenza vaccine Influenza

Seqirus

IM

syringe

vial (10 dose)

0.5 mL

$21.41

N/A

Afluria (age >5 years)

Inactivated quadrivalent influenza vaccine Influenza

Seqirus

IM

syringe

vial (10dose)

0.5 mL

$21.41

Fluarix Quadrivalent (>6 months)

Inactivated Quadrivalent influenza vaccine, ccIIV4

GSK

IM

syringe

0.5 mL

$20.03

FluBlok (18-49 years). Non-Egg Based.

Recombinant quadrivalent influenza vaccine, RIV4

Sanofi

IM

vial (10 dose)

0.5 mL

$32.75

Flucelvax (>4 years)

Inactivated quadrivalent influenza vaccine

(preservative-free, antibiotic-free)

Seqirus

IM

syringe

0.5 mL

$25.31

Flulaval Quadrivalent (>6 months)

Inactivated Quadrivalent influenza vaccine

ID Biomedical Corp. of Quebec

IM

vial (10 dose)

0.5 mL

$20.03

FluMist Quadrivalent (2-49 years)

Live attenuated Influenza vaccine

Astra Zeneca

Intranasal

intranasal sprayer

0.2 mL

$23.70

Fluzone (Quadrivalent, age 6 months - 35 months)

Inactivated quadrivalent vaccine

Sanofi-Pasteur

IM

syringe

0.25 mL

$22.96

Fluzone (Quadrivalent, age > 36 months)

Inactivated quadrivalent vaccine

Sanofi-Pasteur

IM

syringe

vial (10 dose)

0.5 mL

$21.41

N/A

Fluzone** High Dose (for persons ≥ 65 years)

Inactivated trivalent influenza vaccine

Sanofi-Pasteur

IM

syringe

0.5 mL

$56.18

Fluzone** (intradermal)

Inactivated trivalent influenza vaccine

Sanofi-Pasteur

ID

microinjection system

0.1 mL

$21.41

Fluad (> 65 years)

Adjuvanted inactivated trivalent influenza vaccine

Seqirus

IM

syringe

0.5 mL

$57.55

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

**Available upon request from Sanofi Pasteur

PATHOGEN DIRECTED PROTECTION

  • 2018 - 2019 season: recomposed strains compared to 2017-18 season.
    • Trivalent vaccine: A/Michigan/45/2015 (H1N1) pdm09–like virus, A/Singapore/INFIMH-16-0019/2014 (H3N2)-like virus, and B/Colorado/06/2017-like (Victoria lineage) virus.
    • Quadrivalent vaccine: in addition to the above, quadrivalent vaccine includes an additional influenza B virus strain: B/Phuket/3073/2013–like virus (Yamagata lineage).
  • No preferential recommendation is made for one influenza vaccine over another (including children, 2018-2019 season).
  • Approximately 10 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 onset of influenza in the community; vaccine usually available middle to end of August. Preference is to vaccinate by October.

Pediatrics and Adults Vaccines

Age indication

Dosage

Afluria

Trivalent

Quardivalent

> 5 years

> 5 years

0.5 mL IM

0.5 mL IM

Fluarix Quadrivalent

>6 months

0.5 mL IM

Flucelvax Quadrivalent

> 4 years

0.5 mL IM

Flulaval Quadrivalent

2 - 49 years

0.2 mL IN

(0.1 mL per nostril)

FluMist Quadrivalent

≥ 3 years

0.5mL IM

Fluzone Quadrivalent

6 months - 35 months

0.25 mL IM

Fluzone Quadrivalent

> 36 months

0.5 mL IM

ADULT VACCINES ONLY

FluBlok Quadrivalent

18-49 years

0.5 mL IM

Fluzone HIGH DOSE Trivalent

> 65 years

0.5 mL IM

Fluad Adjuvant Trivalent

> 65 years

0.5mL IM

Fluzone**Intradermal

>18 years

0.1 mL ID

Adult BOOSTER

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

Pediatric PRIMARY SERIES

Children: for ages 6 months - 8 years, preferably prior to start of influenza season. See table.

  • Administer 2 doses 4 weeks apart
    • Ages 2-8 years: no preference for any vaccine (LAIV recommended in 2014, no longer the case 2015) for healthy children without contraindications.
  • See table for age and vaccine-specific dosing.

Pediatric BOOSTER

  • Required each season.

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 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; 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.
  • May be co-administered with 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 two 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 "egg-allergic" individual can normally eat baked goods, this means egg allergy is unlikely to be significant regarding receipt of influenza vaccine.
  • LAIV: 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 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 one dose.
    • ACIP emphasize 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 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 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 major infectious cause of death in U.S. (3,000 to 49,000 annually though estimated 80,000 deaths 2017-2018); most are elderly, in nursing homes, or have chronic diseases.
  • Vaccine to healthy adults appears to generally reduce URIs and employee absenteeism; conflicting data on cost effectiveness.
  • Health care workers: vaccination indicated to protect patients and infected 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.

Basis for recommendation

  1. Grohskopf LA et al: Update: ACIP Recommendations for the Use of Quadrivalent Live Attenuated Influenza Vaccine (LAIV4) - United States, 2018-19 Influenza Season. MMWR Morb Mortal Wkly Rep 67:643, 2018  [PMID:29879095]

    Comment: LAIV again an option after a two year hiatus. Although deemed not as efficacious, concern is that children who are needle avoidant not receiving influenza vaccine. CDC will be tracking effectiveness.

  2. Grohskopf LA et al: Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices-United States, 2018-19 Influenza Season. MMWR Recomm Rep 67:1, 2018  [PMID:30141464]

    Comment: Annual recommendations for influenza vaccination for the 2018-19 season. Notable changes include: updated vaccine composition; LAIV4 is once again an appropriate alternative for flu vaccination; a recommendation that persons with a history of an egg allergy may receive any licensed , recommended and age appropriate influenza vaccine; and regulatory changes including newly licensed vaccines.

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Last updated: September 30, 2018

Citation

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TY - ELEC T1 - Influenza vaccine ID - 540287 A1 - Dzintars,Kathryn,Pharm.D. BCPS AU - Auwaerter,Paul,M.D. Y1 - 2018/09/30/ PB - Johns Hopkins ABX Guide UR - https://www.hopkinsguides.com/hopkins/view/Johns_Hopkins_ABX_Guide/540287/all/Influenza_vaccine ER -