VACCINE TYPE

Four major types available in US:

  • 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.
  • Recombinant influenza vaccine (RIV), an egg-free vaccine, is an option for patients with a history of egg allergy of any severity.
    • If RIV is not available, other egg-based influenza vaccine can be given to persons with mild egg allergy (e.g., hives only).
    • Egg allergy history ACIP recommendations: RIV3 and ccIIV3 are made not using embryonated eggs.
      • RIV3 may be used for persons aged 18 through 49 years who have no other contraindications. However, IIV (egg- or cell-culture based) may also be used, with the following additional safety measures.
      • Vaccine should be administered by a health care provider who is familiar with the potential manifestations of egg allergy; and
      • Vaccine recipients should be observed for ≥30 minutes for signs of a reaction after administration of each vaccine dose.
      • Severe reaction history: angioedema, respiratory distress, lightheadedness, or recurrent emesis; or who required epinephrine or another emergency medical intervention, may receive RIV3 if they are aged 18 through 49 years and there are no other contraindications. If RIV3 is not available or the recipient is not within the indicated age range, IIV should be administered by a physician with experience in the recognition and management of severe allergic conditions.
      • Regardless of allergy history, all vaccines should be administered in settings in which personnel and equipment for rapid recognition and treatment of anaphylaxis are available.
      • Persons who are able to eat lightly cooked egg (e.g., scrambled egg) without reaction are unlikely to be allergic.
        • Egg-allergic persons might tolerate egg in baked products (e.g., bread or cake).
        • Tolerance to egg-containing foods does not exclude the possibility of egg allergy.
        • If only hives after exposure to egg, can receive influenza vaccine. Relatively few data are available on use of LAIV in this setting, IIV or trivalent recombinant influenza vaccine (RIV3) should be used.
        • Egg allergy can be confirmed by a consistent medical history of adverse reactions to eggs and egg-containing foods, plus skin and/or blood testing for immunoglobulin E directed against egg proteins.
      • For persons with no known history of exposure to egg, but who are suspected of being egg-allergic on the basis of previously performed allergy testing, consultation with a physician with expertise in the management of allergic conditions should be obtained before vaccination. Alternatively, RIV3 may be administered if the recipient is aged 18 through 49 years.
      • A previous severe allergic reaction to influenza vaccine, regardless of the component suspected of being responsible for the reaction, is a contraindication to future receipt of the vaccine.

OTHER INFORMATION

  • Inactivated influenza vaccine can be used for any persons aged 6 months and older.
  • IDSA guidelines recommend annual vaccination in immunocompromised patient aged > 6 months except for severely immunocompromised (e.g., pts receiving intensive chemotherapy or those who have received anti-B-cell antibodies within 6 months) due to low likelihood of response.
  • Live attenuated virus (LAIV IV, FluMist): not use in the following populations--
    • Ages < 2 yrs and > 49 yrs
    • Immunocompromised
    • Pregnant
    • Anyone receiving aspirin products
    • Persons who have had severe reactions to any influenza vaccine
    • Egg allergy
    • Wheezing in past 12 mos, persons with asthma, patients with chronic pulmonary, cardiovascular, renal, hepatic, neurologic, hematologic or metabolic disorder
      • HCW post LAIV vaccination should not work with severely immunocompromised pts x 7d after immunization and non-HCW who otherwise might be in contact with severely immunocompromised patients should also wait 7d.
      • No reports of transmission person-person.

FORMS

brand name

preparation

manufacturer

route

form

dosage^

cost*

Afluria (age >9 years

Inactivated trivalent influenza vaccine Influenza

CLS limited

IM

syringe

vial (10 dose)

0.5 mL

$12.30

$11.55

Fluarix (≥ 3 yrs)

Inactivated trivalent influenza vaccine Influenza

GSK

IM

syringe

0.5 ml

$16.05

Fluarix Quadrivalent (>3 years)

Inactivated Quadrivalent influenza vaccine, ccIIV3

GSK

IM

syringe

0.5 ml

$16.05

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

Recombinant trivalent influenza vaccine, RIV3

Protein Sciences

IM

vial (10 dose)

0.5 ml

$32.75

FluceIvax (>18 years)

Inactivated trivalent influenza vaccine

(preservative-free, antibiotic-free)

Novartis vaccines and diagnostics

IM

syringe

0.5 ml

$19.68

Flulaval Quadrivalent (>3 years)

Inactivated Quadrivalent influenza vaccine

ID Biomedical Corp. of Quebec

IM

vial (10 dose)

0.5 mL

$15.05

FluMist Quadrivalent (2-49 years)

Live attenuated Influenza vaccine

Medimmune

Intranasal

intranasal sprayer

0.2 mL

$23.70

Fluvirin (for ≥ 4 years)

Inactivated trivalent Influenza vaccine

Norvartis

IM

vial (10 dose)

single-dose syringe (preservative-free)

0.5 mL

$14.01

$15.23

Fluzone (standard formulation, age > 6 months)

Inactivated trivalent influenza vaccine

Sanofi-Pasteur

IM

syringe

vials (10 dose)

0.25 mL ( for > 6 - 35 mos) 0.5 mL ( for >36 mos)

0.5ml vials and 5ml multidose vial

$10.69

Fluzone (Quadrivalent, age > 6 months, pediatric dose)

inactivated quadrivalent vaccine

Sanofi-Pasteur

IM

syringe

$21.70

Fluzone (Quadrivalent, age > 36 months)

inactivated quadrivalent vaccine

Sanofi-Pasteur

IM

syringe

vial (10 dose)

0.5 mL

$17.97

$17.15

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

Inactivated trivalent influenza vaccine

Sanofi-Pasteur

IM

syringe

0.5 ml

$33.49

Fluzone** (intradermal)

Inactivated trivalent influenza vaccine

Sanofi-Pasteur

ID

microinjection system

0.1ml

$17.97

*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

  • Influenza A and B
  • 2015-2016 season: recomposed strains compared to 2014-15 season.
    • Trivalent vaccine: A/California/7/2009 (H1N1)–like virus, A/Switzerland/9715293/2013 (H3N2)-like virus, and B/Phuket/3073/2013-like (B/Yamagata lineage) virus.
    • Quadrivalent vaccine: in addition to the above, quadrivalent vaccine includes an additional influenza B virus strain (B/Brisbane/60/2008–like virus).
  • No preferential recommendation is made for one influenza vaccine over another (including children, 2015-2016 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 a community--by October preferred.

Pediatrics and Adults Vaccines

Age indication

Dosage

Fluzone trivalent Standard formulation

>6 months

For > 6 - 35 months: 0.25 mL IM

For >36 months: 0.5mL IM

Fluzone Quadrivalent

>6 months

For > 6 - 35 months: 0.25 mL IM

For >36 months: 0.5mL IM

FluMist Quadrivalent

2-49 years

0.2 mL intranasally (0.1 mL per nostril)

FluLaval Quadrivalent

>3 years

0.5 mL IM

Fluarix Trivalent

≥ 3 years

0.5 ml IM

Fluarix Quadrivalent

>3 years

0.5ml IM

Flulaval Quadrivalent

>3 years

0.5 ml IM

Fluvirin Trivalent

> 4 years

0.5 ml IM

Afluria Trivalent

>9 years; not recommended for children 6 months to 8 years due to increased risk of febrile reaction.

0.5 mL IM

Vaccines: ADULTS ONLY

FluceIvax Trivalent

>18 years

0.5ml IM

FluBlok Trivalent (Non-Egg Based)

18-49 years

0.5ml IM

Fluzone Trivalent Intradermal

18-64 years

0.1ml Intradermal

Fluzone Trivalent High Dose

≥ 65 years

0.5 ml IM

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 above forms.

  • 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 above 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 [5].
    • 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 [6]; however, no preferential recommendation (yet) is made for high-dose Fluzone over standard dose IIV.

CLINICAL EFFICACY

  • Vaccine efficacy depends on match of epidemic & vaccine strains - good in 14 of 16 past years. 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 [6].
  • In young children (6 to 59 months), intranasally administered live attenuated influenza vaccine was more effective than IM inactivated vaccine with 54.9% fewer cases of cultured-confirmed influenza.
  • 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 [7].

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 US (3,000 to 49,000 annually); most are elderly, in nursing homes, or have chronic diseases.
  • Vaccine to healthy adults appears to generally reduce URI’s 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: Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices (ACIP) - United States, 2014-15 Influenza Season. MMWR Morb Mortal Wkly Rep 63:691, 2014  [PMID:25121712]

    Comment: Updated ACIP recommendations from 2013-2014 season: 1) antigenic composition of U.S. seasonal influenza vaccines; 2) vaccine dose considerations for children aged 6 months through 8 years; and 3) a preference for the use, when immediately available, of live attenuated influenza vaccine (LAIV) for healthy children aged 2 through 8 years, to be implemented as feasible for the 2014–15 season but not later than the 2015–16 season. Information regarding issues related to influenza vaccination not addressed in this report is available in the 2013 ACIP seasonal influenza recommendations.

  2. Grohskopf LA et al: Prevention and Control of Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices, United States, 2015-16 Influenza Season. MMWR Morb Mortal Wkly Rep 64:818, 2015  [PMID:26247435]

    Comment: Update to 2014 recommendations--major items include a) no preference in children 2-8 yrs for LAIV or IIV products, b) don’t wait for a specific product if an appropriate one is available.

References

  1. Monto AS et al: Comparative efficacy of inactivated and live attenuated influenza vaccines. N Engl J Med 361:1260, 2009  [PMID:19776407]

    Comment: A randomized, double-blind, placebo-controlled trial, compared the inactivated and live attenuated influenza vaccines in healthy adults during the 2007/2008 influenza season. The inactivated vaccine was superior to the attenuated live intranasal vaccine with an efficacy of 72% (95% CI, 49 to 84) vs. 29% (95% CI, -14 to 55).

  2. Appiah GD et al: Influenza activity - United States, 2014-15 season and composition of the 2015-16 influenza vaccine. MMWR Morb Mortal Wkly Rep 64:583, 2015  [PMID:26042650]

    Comment: Influenza A (H3N2) was the major circulating strain in 2014 and account for the greatest mortality impact in age group > 65 years. This was not a match with the recommended vaccine for that year, accounting for increased cases and severity.

  3. Centers for Disease Control and Prevention (CDC): Preliminary results: surveillance for Guillain-Barré syndrome after receipt of influenza A (H1N1) 2009 monovalent vaccine - United States, 2009-2010. MMWR Morb Mortal Wkly Rep 59:657, 2010  [PMID:20520590]

    Comment: Federal surveillance systems found no clear signals that this influenza immunization program resulted in higher GBS case incidence.

  4. DiazGranados CA et al: Efficacy of high-dose versus standard-dose influenza vaccine in older adults. N Engl J Med 371:635, 2014  [PMID:25119609]

    Comment: Known to yield higher titers in the elderly, this large study of 21,989 people divided IV3-HD (60 μg of hemagglutinin per strain) with standard-dose trivalent, inactivated influenza vaccine (IIV3-SD [15 μg of hemagglutinin per strain]) found clinical efficacy with HD. 228 participants in the IIV3-HD group (1.4%) and 301 participants in the IIV3-SD group (1.9%) had laboratory-confirmed influenza caused by any viral type or subtype associated with a protocol-defined influenza-like illness (relative efficacy, 24.2%; 95% confidence interval [CI], 9.7 to 36.5). At least one serious adverse event during the safety surveillance period was reported by 1323 (8.3%) of the participants in the IIV3-HD group, as compared with 1442 (9.0%) of the participants in the IIV3-SD group (relative risk, 0.92; 95% CI, 0.85 to 0.99) suggesting equivalent safety.

  5. Nichol KL et al: Effectiveness of live, attenuated intranasal influenza virus vaccine in healthy, working adults: a randomized controlled trial. JAMA 282:137, 1999  [PMID:10411194]

    Comment: Often cited study showing recipients had fewer URIs, not just influenza. Reason not known.

  6. Belshe RB et al: Live attenuated versus inactivated influenza vaccine in infants and young children. N Engl J Med 356:685, 2007  [PMID:17301299]

    Comment: The safety and efficacy of intranasally administered live attenuated influenza vaccine was compared to inactivated vaccine in 8352 infants and young children (6 to 59 months). Intranasally administered live attenuated influenza vaccine was more effective with 54.9% fewer cases of cultured-confirmed influenza compared to those who received inactivated vaccine (153 vs. 338 cases, P<0.001). Among children 6 to 11 months of age, there was a trend toward a higher incidence of wheezing and a significantly higher rate of hospitalization during the 180 days post vaccination.

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Last updated: August 25, 2015