The Medical Letter on Drugs and Therapeutics
Influenza Vaccine for 2019-2020
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Annual vaccination against influenza A and B viruses is recommended for everyone ≥6 months old without a contraindication.1 Available vaccines and recommendations for specific patient populations for the 2019-2020 season are listed in Tables 2 and 3.

TIMING — In the US, influenza vaccine should be offered by the end of October and continue to be offered for as long as influenza is circulating in the community. In most adults, serum antibody levels peak about two weeks after vaccination.1 Early vaccination (i.e., in July or August) may result in suboptimal immunity before the end of the influenza season, especially in older adults. Children who require 2 doses (see Table 3, footnote 2) should receive the first dose as early as possible, so that the second dose can be given by the end of October.

COMPOSITION — All seasonal influenza vaccines available in the US contain antigens of the same two influenza A viruses. Influenza A viruses are responsible for the majority of influenza-related morbidity and mortality, particularly in infants and older adults.2

Trivalent vaccines contain only one influenza B virus antigen. Quadrivalent vaccines contain influenza B virus antigens from both genetic lineages that have been circulating globally since the 1980s, increasing the likelihood that the vaccine will provide protection against currently circulating strains.3,4 Children are more likely than adults to become infected with influenza B.2

EFFECTIVENESS — Influenza vaccination reduces the incidence of laboratory-confirmed influenza and can reduce the risk of serious complications and death associated with influenza illness in children and adults.5-8

The effectiveness of seasonal influenza vaccine in preventing laboratory-confirmed influenza illness depends on several factors, including the match between the vaccine and circulating strains 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 the risk of influenza-related hospitalization and death.9-11 The antigens selected for inclusion in the seasonal vaccine can be altered slightly during production of egg-based vaccines, possibly resulting in a less desirable match between the vaccine and circulating strains.

The interim adjusted overall effectiveness of the influenza vaccine in preventing laboratory-confirmed influenza infection during the 2018-2019 season was 47% (61% in children 6 months-17 years old and 24% in adults ≥50 years old). Effectiveness against group A viruses was 44% (H3N2) and 46% (H1N1).12

LIVE-ATTENUATED VACCINE — FluMist Quadrivalent, the intranasally administered live-attenuated influenza vaccine, is FDA-approved for use in healthy nonpregnant persons 2-49 years old (see Table 2, footnote 19 for contraindications and precautions). The Advisory Committee on Immunization Practices (ACIP) and the American Academy of Pediatrics (AAP) recommend the live-attenuated vaccine as an option this season.1,13 In previous seasons, there were concerns about the efficacy of the live-attenuated vaccine against influenza A(H1N1)pdm09-like viruses, and the ACIP advised against its use during the 2016-2017 and 2017-2018 seasons.14-16 For the 2018-2019 season, the ACIP recommended the live-attenuated vaccine once again as an option based on a change in the A(H1N1)pdm09-like strain to one with improved replicative fitness.17 The A(H1N1)pdm09-like virus contained in this season's live-attenuated vaccine is different from the one used in last year's vaccine.

OLDER ADULTS — Older adults may have weaker immunogenic responses to influenza vaccination than younger adults, and their antibody levels may decline more rapidly.18,19 Recombinant, high-dose, and adjuvanted vaccines can improve antibody responses in older patients (see Table 4).

Recombinant Vaccine – Flublok Quadrivalent, a recombinant inactivated vaccine produced without the use of influenza virus or chicken eggs, contains three times the amount of antigen included in standard-dose influenza vaccines and is FDA-approved for use in persons ≥18 years old. In adults 50-64 years old, the trivalent formulation of Flublok (no longer available) produced greater antibody responses to influenza A antigens than standard-dose trivalent vaccines.20 In a randomized, double-blind trial during the A/H3N2-predominant 2014-2015 season, the recombinant quadrivalent vaccine was 30% more effective than a standard-dose unadjuvanted quadrivalent vaccine in preventing polymerase chain reaction (PCR)-confirmed influenza illness in 8604 adults ≥50 years old (42% more effective in persons 50-64 years old and 17% more effective in those ≥65 years old).21

High-Dose Vaccine – Fluzone High-Dose, an inactivated trivalent vaccine that contains four times the amount of antigen included in standard-dose influenza vaccines, is FDA-approved for use in persons ≥65 years old. In a randomized, double-blind trial in 31,989 adults ≥65 years old during two influenza seasons, 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.22 In observational studies and one meta-analysis in adults ≥65 years old, the high-dose influenza vaccine was associated with reduced risk of respiratory-related and all-cause hospital admissions and death compared to standard-dose vaccines.23-26

Adjuvanted Vaccine – Fluad, an adjuvanted inactivated trivalent influenza vaccine, is FDA-approved for use in persons ≥65 years old.27 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 an unadjuvanted trivalent vaccine, but the prespecified criteria for superiority was not met.28 In observational studies, older adults who received the adjuvanted trivalent influenza vaccine were less likely than those who received an unadjuvanted standard-dose trivalent vaccine to develop symptomatic influenza illness or be hospitalized for influenza or pneumonia.29,30 Randomized controlled trials demonstrating the efficacy of the adjuvanted vaccine in preventing laboratory-confirmed influenza are lacking.

PREGNANCY — Vaccination protects pregnant women against influenza-associated illness, which can be especially severe during pregnancy, and protects their infants for up to the first 6 months of life.31-33

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 2010-2011 and 2011-2012 influenza seasons, administration of an inactivated influenza vaccine containing an A/H1N1pdm09 antigen was modestly, but statistically significantly, associated with spontaneous abortion in the 28 days after vaccination among women who had received an A/H1N1pdm09-containing vaccine during the previous season.34,1 In a larger follow-up study during the 2012-2013, 2013-2014, and 2014-2015 influenza seasons, influenza vaccine was not associated with spontaneous abortion regardless of previous season vaccination.35 The ACIP and the American College of Obstetricians and Gynecologists recommend vaccinating pregnant women against influenza without regard to the trimester of pregnancy,36,37 but they should not receive the live-attenuated vaccine.

ALLERGY — A history of severe allergic reaction to any component of the influenza vaccine is listed as a contraindication in the labeling of all influenza vaccines. 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.38 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 with supervision by a healthcare provider experienced in recognizing and managing severe allergic reactions. The recombinant vaccine (Flublok Quadrivalent) and the cell culture-based inactivated vaccine (Flucelvax Quadrivalent) are not prepared by propagation of virus in embryonated eggs.

IMMUNOCOMPROMISED PERSONS — The live-attenuated influenza vaccine should not be used in immunocompromised persons. 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.1

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.39 In a randomized trial in 279 patients with rheumatoid arthritis, immune responses to the influenza vaccine were higher in patients given a high-dose vaccine than in those given a standard-dose vaccine.40

ADVERSE EFFECTS — Influenza vaccination has been associated with Guillain-Barré syndrome, but the absolute risk is very low (about 1-2 additional cases per million persons vaccinated). Influenza infection itself has been associated with the syndrome (about 17 cases per million influenza infection encounters).41,42

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. Pain and tenderness at the injection site occurred more frequently with Fluad than with an unadjuvanted vaccine. Delivery of Afluria by needle-free jet injector has resulted in more mild to moderate local reactions than delivery by standard needle and syringe.

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.

WITH OTHER VACCINES — Inactivated and recombinant influenza vaccines can be administered concomitantly or sequentially with live or other inactivated 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. Use of an unadjuvanted influenza vaccine might be considered in persons receiving another adjuvanted vaccine (e.g., Shingrix, Heplisav B) because of the theoretical possibility of increased reactogenicity.

WITH INFLUENZA ANTIVIRALS — Use of influenza antiviral drugs (a neuraminidase inhibitor or baloxavir) within 48 hours before or <2 weeks after administration of the intranasal live-attenuated influenza vaccine could inhibit replication of the vaccine virus, reducing the vaccine's efficacy.

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. The intranasal live-attenuated vaccine is a recommended option for the 2019-2020 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 to be more effective for prevention of laboratory-confirmed influenza in older persons in randomized controlled trials.


  1. LA Grohskopf et al. Prevention and control of seasonal influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices – United States, 2019-20 influenza season. MMWR Recomm Rep 2019; 68:1.
  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. B Flannery et al. Influenza vaccine effectiveness against pediatric deaths: 2010-2014. Pediatrics 2017; 139:e20164244.
  7. AP Campbell et al. Influenza vaccine effectiveness against laboratory-confirmed influenza in children hospitalized with respiratory illness in the United States, 2016-17 and 2017-18 seasons. Presented at IDWeek, October 2-6, 2019, Washington, DC. Abstract 899. Available at: Accessed October 9, 2019.
  8. S Garg et al. Influenza vaccine reduces risk of severe outcomes among adults hospitalized with influenza A(H1N1)pdm09, FluServ-NET, 2013-2018. Presented at IDWeek, October 2-6, 2019, Washington, DC. Abstract 898. Available at: www. Accessed October 9, 2019.
  9. EA Belongia et al. Variable influenza vaccine effectiveness by subtype: a systematic review and meta-analysis of testnegative design studies. Lancet Infect Dis 2016; 16:942.
  10. M Darvishian et al. Effectiveness of seasonal influenza vaccine in community-dwelling elderly people: a meta-analysis of testnegative design case-control studies. Lancet Infect Dis 2014; 14:1228.
  11. MA Rolfes et al. Effects of influenza vaccination in the United States during the 2017-2018 influenza season. Clin Infect Dis 2019 February 2 (epub).
  12. JD Doyle et al. Interim estimates of 2018-19 seasonal influenza vaccine effectiveness – United States, February 2019. MMWR Morb Mortal Wkly Rep 2019; 68:135.
  13. Committee on Infectious Diseases. Recommendations for prevention and control of influenza in children, 2019-2020. Pediatrics 2019; 144:e20192478.
  14. JR Chung et al. Live attenuated and inactivated influenza vaccine effectiveness. Pediatrics 2019; 143:e20182094.
  15. ML Jackson et al. Influenza vaccine effectiveness in the United States during the 2015-2016 season. N Engl J Med 2017; 377:534.
  16. 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.
  17. 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.
  18. 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.
  19. 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.
  20. 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.
  21. LM Dunkle et al. Efficacy of recombinant influenza vaccine in adults 50 years of age or older. N Engl J Med 2017; 376:2427.
  22. CA DiazGranados et al. Efficacy of high-dose versus standard-dose influenza vaccine in older adults. N Engl J Med 2014; 371:635.
  23. 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.
  24. 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.
  25. 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.
  26. Y Young-Xu et al. Analysis of relative effectiveness of high-dose versus standard-dose influenza vaccines using an instrumental variable method. Vaccine 2019; 37:1484.
  27. Fluad – an adjuvanted seasonal influenza vaccine for older adults. Med Lett Drugs Ther 2016; 58:8.
  28. 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.
  29. PG Van Buynder et al. The comparative effectiveness of adjuvanted and unadjuvanted trivalent inactivated influenza vaccine (TIV) in the elderly. Vaccine 2013; 31:6122.
  30. S Mannino et al. Effectiveness of adjuvanted influenza vaccination in elderly subjects in northern Italy. Am J Epidemiol 2012; 176:527.
  31. 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.
  32. 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 2019; 68:1444.
  33. SA Madhi et al. Influenza vaccination of pregnant women and protection of their infants. N Engl J Med 2014; 371:918.
  34. 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.
  35. J Donahue et al. Inactivated influenza vaccine and spontaneous abortion in the Vaccine Safety Datalink in 2012-13, 2013-14, and 2014-15. Vaccine 2019; 37:6673.
  36. CDC. Flu vaccination & addressing concerns pregnant women might have about flu vaccine safety. Available at: Accessed August 28, 2019.
  37. ACOG Committee Opinion No. 732: influenza vaccination during pregnancy. Obstet Gynecol 2018; 131:e109.
  38. M Greenhawt et al. Administration of influenza vaccines to egg allergic recipients: a practice parameter update 2017. Ann Allergy Asthma Immunol 2018; 120:49.
  39. 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.
  40. I Colmegna et al. Efficacy of high-dose versus standard-dose influenza vaccine in seropositive rheumatoid arthritis patients. Arthritis Rheumatol 2018; 70 (suppl 10). Abstract 837.
  41. 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.
  42. 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.
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