The Medical Letter on Drugs and Therapeutics
FROM
ISSUE
1558
Influenza Vaccine for 2018-2019
Download PDF:   US English
 Select a term to see related articles  Afluria   Agriflu   Fluad   Fluarix   Flublok   FluceIvax   flulaval   FluMist   Fluzone High-Dose   influenza   Influenza vaccine   Influvac 
Revised 10/25/18: Tables 2 and 4 were revised to reflect the FDA's recent approval of Afluria Quadrivalent for person ≥6 months old.

Routine annual vaccination against influenza A and B viruses is recommended for everyone ≥6 months old.1 Recommendations for the current season for specific patient populations are listed in Tables 2 and 4.

TIMING — In the US, influenza vaccine should be offered by the end of October and continue to be offered as long as influenza is circulating in the community. In most adults, serum antibody levels peak about two weeks after vaccination.1

COMPOSITION — All seasonal influenza vaccines available in the US contain the same two influenza A virus antigens. Influenza A viruses are responsible for the majority of influenza-related morbidity and mortality, particularly in infants and older adults; influenza A(H3N2) has been associated with the highest rates of morbidity and mortality in older adults.2

Trivalent vaccines contain only one influenza B virus antigen (Victoria lineage). Quadrivalent vaccines contain influenza B virus antigens from both genetic lineages that have been circulating globally since the 1980s (Victoria and Yamagata), increasing the likelihood that the vaccine will provide protection against currently circulating strains.3,4 Influenza B viruses primarily infect children.2

EFFECTIVENESS — The effectiveness of seasonal influenza vaccine in preventing laboratory-confirmed influenza illness depends mainly on the match between the vaccine and circulating strains (type/subtype and antigenic similarity) and the immunologic response of the recipient. Vaccine effectiveness is greatest when the match is close, but even when it is suboptimal, vaccination can still substantially reduce influenza-related hospitalization and death.5-9 (The vaccine strains selected for inclusion in the seasonal vaccine can mutate during production of egg-based vaccines, possibly resulting in a lower match between the vaccine and circulating strains.)

The interim adjusted overall effectiveness of the seasonal influenza vaccine in preventing laboratory-confirmed influenza for the 2017-18 season was 40%; effectiveness against group A viruses was 24% (H3N2) and 65% (H1N1) and against group B viruses was 49%.10

LIVE-ATTENUATED VACCINE — The intranasal live-attenuated influenza vaccine (Flumist Quadrivalent) is FDA-approved for healthy nonpregnant persons 2-49 years old (see Table 4, footnote 17 for contraindications). In recent seasons, there have been concerns about the efficacy of the live-attenuated vaccine against influenza A(H1N1)pdm09-like viruses, and the Advisory Committee on Immunization Practices (ACIP) advised against its use during the 2016-17 and 2017-18 seasons.11-13

This season the ACIP is once again recommending the live-attenuated influenza vaccine as an option. The 2018-19 quadrivalent live-attenuated vaccine contains a new A(H1N1)pdm09-like virus that was shed by a higher proportion of children after vaccination and induced significantly greater antibody responses than the previous live-attenuated vaccine, but clinical data demonstrating improved effectiveness are not yet available.14 The American Academy of Pediatrics and the American Academy of Family Physicians recommend use of the live-attenuated vaccine only for persons who would not otherwise be vaccinated.15,16

OLDER ADULTS — Older adults may have weaker immunogenic responses to influenza vaccination than younger adults, and their antibody levels may decline more rapidly.17,18 Recombinant, high-dose, and adjuvanted vaccines can improve antibody responses in these patients.

Recombinant Vaccine – Flublok Quadrivalent, a recombinant vaccine produced without the use of influenza virus or chicken eggs, contains three times the amount of antigen included in standard-dose vaccines and is FDA-approved for use in persons ≥18 years old. In adults 50-64 years old, the trivalent formulation of Flublok produced greater antibody responses to influenza A antigens than standard-dose trivalent vaccines.19 In a randomized, double-blind trial during the A/H3N2-predominant 2014-15 season, the recombinant quadrivalent vaccine was 30% more effective than a standard-dose unadjuvanted quadrivalent vaccine in preventing laboratory-confirmed influenza illness in 8604 adults ≥50 years old (42% more effective in those 50-64 years old and 17% more effective in those ≥65 years old).20

High-Dose Vaccine – Fluzone High-Dose, an inactivated trivalent vaccine that contains four times the amount of antigen included in standard-dose vaccines, is FDA-approved for use in persons ≥65 years old. In a randomized, double-blind trial during two influenza seasons in 31,989 adults ≥65 years old, the high-dose vaccine induced significantly greater antibody responses than a standard-dose trivalent inactivated vaccine and was 24.2% more effective in preventing laboratory-confirmed influenza illness.21 In recent studies in adults ≥65 years old, the high-dose influenza vaccine appeared to reduce the risk of respiratory-related and all-cause hospital admissions and death, compared to standard-dose vaccines.22-24

In a randomized trial in 172 solid-organ transplant recipients ≥18 years old, the high-dose vaccine induced significantly greater antibody responses than a standard-dose vaccine.25

Adjuvanted Vaccine – The adjuvanted trivalent influenza vaccine (Fluad) is FDA-approved for use in persons ≥65 years old.26 It contains MF59, an oil-in-water emulsion of squalene oil that increases the immune response by recruiting antigen-presenting cells to the injection site and promoting uptake of influenza virus antigens. In a randomized trial in 7082 adults ≥65 years old, the adjuvanted vaccine elicited significantly greater antibody responses against all three influenza strains than the unadjuvanted trivalent vaccine, but the differences did not meet the prespecified criteria for superiority.27 In observational studies, older adults who received the adjuvanted trivalent influenza vaccine were less likely to develop symptomatic influenza illness or be hospitalized for influenza or pneumonia than those who received an unadjuvanted standard-dose trivalent vaccine.28,29

CARDIOVASCULAR BENEFITS — In meta-analyses of randomized trials, influenza vaccination was associated with a reduced risk of major adverse cardiovascular events and death in patients at high risk for cardiovascular disease. The reduction in risk was greatest in those with a recent history of acute coronary syndrome.30,31

PREGNANCY — Vaccination of pregnant women not only protects them against influenza-associated illness, which can be especially severe during pregnancy, but also protects their infants for up to the first 6 months of life.32-34

Most studies have not found an association between influenza vaccination and adverse pregnancy outcomes, but data demonstrating the safety of vaccination during the first trimester are limited. In one case-control study of 485 cases of spontaneous abortion (gestational age 5 to <20 weeks) that occurred during the 2010-11 and 2011-12 influenza seasons, administration of an inactivated influenza vaccine containing H1N1pdm09 was associated with an increased risk of miscarriage in the 28 days after vaccination among women who had received an H1N1pdm09-containing vaccine during the previous season35; a causal relationship has not been established.1 The ACIP and the American College of Obstetricians and Gynecologists continue to recommend influenza vaccination in pregnant women without regard to the trimester of pregnancy.36,37 The live-attenuated vaccine should not be used in pregnant women.

ADVERSE EFFECTS — Influenza vaccination has been associated with Guillain-Barré syndrome, but the absolute risk is very low, and influenza infection itself has also been associated with the syndrome.38,39

Except for soreness at the injection site, adverse reactions to inactivated influenza vaccines are uncommon. In clinical trials, Fluzone High-Dose caused more injection-site reactions than standard-dose influenza vaccines. Delivery of Afluria by needle-free jet injector has resulted in more mild to moderate local reactions than delivery by standard needle and syringe. Pain and tenderness at the injection site occurred more frequently with Fluad than with an unadjuvanted vaccine.

The most common adverse reactions associated with the live-attenuated vaccine are runny nose, nasal congestion, fever, and sore throat. The vaccine can increase the risk of wheezing, especially in children <5 years old with recurrent wheezing and in persons of any age with asthma. Persons vaccinated with the live-attenuated vaccine may shed the vaccine-strain virus for a few days after vaccination, but person-to-person transmission has been rare, and serious illness resulting from transmission has not been reported. Nevertheless, persons who care for severely immunocompromised patients in protected environments should not receive the live-attenuated vaccine or should avoid contact with such patients for 7 days after receiving it.

ALLERGY — A history of severe allergic reaction to any component of the influenza vaccine is a contraindication to vaccination. In 28 studies that included 4315 patients with egg allergy (656 with a history of a severe allergic reaction), there were no reports of anaphylaxis after administration of egg-based inactivated influenza vaccines; some mild reactions did occur.40 The ACIP, the American Academy of Allergy, Asthma and Immunology, and the American College of Allergy, Asthma and Immunology state that any age-appropriate influenza vaccine can be administered to persons who report a history of hives related to egg exposure. Persons with more severe egg allergy can also receive any age-appropriate influenza vaccine, but they should be vaccinated in a healthcare setting. The recombinant vaccine (Flublok Quadrivalent) contains no egg protein.

IMMUNOCOMPROMISED PERSONS — Immunocompromised persons should not receive the live-attenuated influenza vaccine. Inactivated vaccines are generally considered safe for use in such persons, but the immune response may be reduced. Separation in time of influenza vaccination from an immunocompromising intervention might be considered.

WITH OTHER VACCINES — Inactivated and recombinant influenza vaccines can be administered concomitantly or sequentially with other inactivated or live vaccines. The live-attenuated influenza vaccine can be given simultaneously with inactivated or other live vaccines. Other live vaccines not administered on the same day should be given at least 4 weeks later. Because of the theoretical possibility of increased reactogenicity in patients receiving another adjuvanted vaccine (e.g., Shingrix), use of an unadjuvanted influenza vaccine might be considered in such patients.

CONCLUSION — Vaccination against seasonal influenza is recommended for all persons ≥6 months old, including pregnant women. Quadrivalent vaccines offer broader coverage against influenza B viruses, which primarily infect children. The intranasal live-attenuated vaccine is once again an ACIP-recommended option for the 2018-19 season. Recombinant, high-dose, and adjuvanted vaccines elicit greater antibody responses than standard-dose unadjuvanted vaccines in persons ≥65 years old, and the high-dose and recombinant vaccines have been shown in randomized controlled trials to be more effective in older patients in preventing laboratory-confirmed influenza.

  1. LA Grohskopf 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 2018; 67:1.
  2. W Schaffner et al. Seasonal influenza immunisation: strategies for older adults. Int J Clin Pract 2018; 72:e13249.
  3. R Ray et al. A review of the value of quadrivalent influenza vaccines and their potential contribution to influenza control. Hum Vaccin Immunother 2017; 13:1640.
  4. WEP Beyer et al. Rationale for two influenza B lineages in seasonal vaccines: a meta-regression study on immunogenicity and controlled field trials. Vaccine 2017; 35:4167.
  5. C Arriola et al. Influenza vaccination modifies disease severity among community-dwelling adults hospitalized with influenza. Clin Infect Dis 2017; 65:1289.
  6. EA Belongia et al. Variable influenza vaccine effectiveness by subtype: a systematic review and meta-analysis of test-negative design studies. Lancet Infect Dis 2016; 16:942.
  7. M Darvishian et al. Effectiveness of seasonal influenza vaccine in community-dwelling elderly people: a meta-analysis of test-negative design case-control studies. Lancet Infect Dis 2014; 14:1228.
  8. B Flannery et al. Influenza vaccine effectiveness against pediatric deaths: 2010-2014. Pediatrics 2017; 139:e20164244.
  9. AM Fry et al. Modeling the effect of different vaccine effectiveness estimates on the number of vaccine-prevented influenza-associated hospitalizations in older adults. Clin Infect Dis 2014; 59:406.
  10. B Flannery et al. Interim estimates of 2017-18 seasonal influenza vaccine effectiveness – United States, February 2018. MMWR Morb Mortal Wkly Rep 2018; 67:180.
  11. JR Chung et al. Seasonal effectiveness of live attenuated and inactivated influenza vaccine. Pediatrics 2016; 137:e20153279.
  12. ML Jackson et al. Influenza vaccine effectiveness in the United States during the 2015-2016 season. N Engl J Med 2017; 377:534.
  13. SA Buchan et al. Effectiveness of live attenuated vs inactivated influenza vaccines in children during the 2012-2013 through 2015-2016 influenza seasons in Alberta, Canada: a Canadian Immunization Research Network (CIRN) study. JAMA Pediatr 2018; 172:e181514.
  14. LA Grohskopf 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 2018; 67:643.
  15. Committee on Infectious Diseases. Recommendations for prevention and control of influenza in children, 2018-2019. Pediatrics 2018; 142:e20182367.
  16. Prevention and control of seasonal influenza with vaccines. AAFP recommendations for the 2018-2019 influenza season. Available at: www.aafp.org. Accessed October 11, 2018.
  17. B Young et al. Do antibody responses to the influenza vaccine persist year-round in the elderly? A systematic review and meta-analysis. Vaccine 2017; 35:212.
  18. JY Song et al. Long-term immunogenicity of influenza vaccine among the elderly: risk factors for poor immune response and persistence. Vaccine 2010; 28:3929.
  19. R Baxter et al. Evaluation of the safety, reactogenicity and immunogenicity of FluBlok trivalent recombinant baculovirus-expressed hemagglutinin influenza vaccine administered intramuscularly to healthy adults 50-64 years of age. Vaccine 2011; 29:2272.
  20. LM Dunkle et al. Efficacy of recombinant influenza vaccine in adults 50 years of age or older. N Engl J Med 2017; 376:2427.
  21. CA DiazGranados et al. Efficacy of high-dose versus standard-dose influenza vaccine in older adults. N Engl J Med 2014; 371:635.
  22. S Gravenstein et al. Comparative effectiveness of high-dose versus standard-dose influenza vaccination on numbers of US nursing home residents admitted to hospital: a cluster-randomised trial. Lancet Respir Med 2017; 5:738.
  23. DK Shay et al. Comparative effectiveness of high-dose versus standard-dose influenza vaccines among US Medicare beneficiaries in preventing postinfluenza deaths during 2012-2013 and 2013-2014. J Infect Dis 2017; 215:510.
  24. JKH Lee et al. Efficacy and effectiveness of high-dose versus standard-dose influenza vaccination for older adults: a systematic review and meta-analysis. Expert Rev Vaccines 2018; 17:435.
  25. Y Natori et al. A double-blind, randomized trial of high-dose vs standard-dose influenza vaccine in adult solid-organ transplant recipients. Clin Infect Dis 2018; 66:1698.
  26. Fluad – an adjuvanted seasonal influenza vaccine for older adults. Med Lett Drugs Ther 2016; 58:8.
  27. SE Frey et al. Comparison of the safety and immunogenicity of an MF59-adjuvanted with a non-adjuvanted seasonal influenza vaccine in elderly subjects. Vaccine 2014; 32:5027.
  28. PG Van Buynder et al. The comparative effectiveness of adjuvanted and unadjuvanted trivalent inactivated influenza vaccine (TIV) in the elderly. Vaccine 2013; 31:6122.
  29. S Mannino et al. Effectiveness of adjuvanted influenza vaccination in elderly subjects in northern Italy. Am J Epidemiol 2012; 176:527.
  30. JA Udell et al. Association between influenza vaccination and cardiovascular outcomes in high-risk patients: a meta-analysis. JAMA 2013; 310:1711.
  31. C Clar et al. Influenza vaccines for preventing cardiovascular disease. Cochrane Database Syst Rev 2015; 5:CD005050.
  32. MG Thompson et al. Effectiveness of seasonal trivalent influenza vaccine for preventing influenza virus illness among pregnant women: a population-based case-control study during the 2010-2011 and 2011-2012 influenza seasons. Clin Infect Dis 2014; 58:449.
  33. MG Thompson et al. Influenza vaccine effectiveness in preventing influenza-associated hospitalizations during pregnancy: a multi-country retrospective test negative design study, 2010-2016. Clin Infect Dis 2018 October 11 (epub).
  34. SA Madhi et al. Influenza vaccination of pregnant women and protection of their infants. N Engl J Med 2014; 371:918.
  35. JG Donahue et al. Association of spontaneous abortion with receipt of inactivated influenza vaccine containing H1N1pdm09 in 2010-11 and 2011-12. Vaccine 2017; 35:5314.
  36. CDC. Flu vaccination & possible safety signal: information & guidance for health care providers. Available at: www.cdc.gov. Accessed October 11, 2018.
  37. Committee Opinion No. 732: influenza vaccination during pregnancy. Obstet Gynecol 2018; 131:e109.
  38. JC Kwong et al. Risk of Guillain-Barré syndrome after seasonal influenza vaccination and influenza health-care encounters: a self-controlled study. Lancet Infect Dis 2013; 13:769.
  39. LL Polakowski et al. Chart-confirmed Guillain-Barré syndrome after 2009 H1N1 influenza vaccination among the Medicare population, 2009-2010. Am J Epidemiol 2013; 178:962.
  40. M Greenhawt et al. Administration of influenza vaccines to egg allergic recipients: a practice parameter update 2017. Ann Allergy Asthma Immunol 2018; 120:49.
© The Medical Letter, Inc. All Rights Reserved.
This article has been freely provided.