Seasonal Influenza Vaccine Safety: A Summary for Clinicians

CDC and FDA monitor the safety of all vaccines licensed in the United States, including seasonal influenza vaccines. This summary provides information on:

  • Safety of inactivated influenza vaccine (IIV), cell culture-based inactivated influenza vaccine (ccIIV3), recombinant influenza vaccine (RIV), and live attenuated influenza vaccine (LAIV), including adverse events following immunization, contraindications, and precautions.
    • Adverse Event Following Immunization (AEFI): Adverse health events or health problems that occur following or during administration of a vaccine, that might be caused by the vaccine or might be coincidental and not related to vaccination.
    • Contraindications: A condition in a vaccine recipient that increases the risk for a serious adverse reaction. A vaccine should not be administered when a contraindication is present.
    • Precautions: A condition in a vaccine recipient that might increase the risk for a serious adverse reaction or that might compromise the ability of the vaccine to produce immunity.
  • Safe vaccine administration.
  • Reporting adverse events to the Vaccine Adverse Event Reporting System (VAERS).
  • Additional resources for clinicians about influenza vaccine safety .

Inactivated Influenza Vaccine (IIV)

Studies support the safety of annual IIV vaccination in children and adults. IIV is administered as an injection and may cause pain, redness, and swelling at the injection site, and may also cause fever, malaise and myalgias, which are usually mild and go away on their own. IIV contains inactivated virus and cannot cause influenza.

  • Pain and other injection site reactions are frequently reported after IIV vaccination in both children and adults. In IIV clinical trials, up to 65% of people vaccinated with IIV experience pain at the injection site during the first week after vaccination which usually did not interfere with activity.
  • Fever, malaise, myalgia, and other systemic symptoms can occur after vaccination with IIV, most often affecting individuals who have had no previous exposure to the influenza virus antigens in the vaccine (e.g., young children). In adults, the rate of having these symptoms is similar after IIV and after a placebo injection.
  • Vaccine components can on rare occasions cause allergic reactions (immediate hypersensitivity). Manifestations of immediate hypersensitivity range from mild urticaria (hives) and angioedema (swelling beneath the skin) to anaphylaxis.
  • In some seasons, IIV has been associated with febrile seizures in young children, particularly when given together with 13-valent pneumococcal conjugate vaccine (PCV13) and diphtheria, tetanus and pertussis (DTaP) vaccines. Flu vaccine composition often changes year-to-year, and CDC and FDA will continue to closely monitor the safety of influenza vaccines each season.
  • Guillain–Barré Syndrome (GBS) following IIV occurs rarely. The cause of GBS, a serious neurological condition that can cause paralysis, is unknown, however, gastrointestinal and upper respiratory infections are known risk factors.
  • IIV, like other injections, can also cause syncope (fainting).

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Cell Culture-based Inactivated Influenza Vaccine (ccIIV3)

Flucelvax (ccIIV3) is the first U.S.-licensed (trivalent inactivated) influenza vaccine manufactured using cell culture technology. It is indicated for use in individuals 18 years of age and older. ccIIV3 is administered as an injection and may cause pain, redness, and swelling at the injection site, and may also cause fever, malaise and myalgias which are usually mild and self-limited. ccIIV3 cannot cause influenza.

  • The most common (≥10%) local and systemic reactions in adults 18-64 years of age were injection site pain (28%), injection site erythema (13%), headache (16%), fatigue (12%), muscle pain (11%) and malaise (10%).

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Recombinant Influenza Vaccine (RIV)

FluBlok (RIV) is a recombinant hemagglutinin influenza vaccine available as a trivalent formulation. RIV does not contain any egg protein.  RIV is indicated for active immunization against disease caused by influenza virus subtypes A and type B and is approved for use in individuals 18 years of age and older. RIV is administered as an injection and may cause pain, redness, and swelling at the injection site, and may also cause fever, malaise and myalgias which are usually mild and self-limited. RIV cannot cause influenza.

Read more about how recombinant flu vaccines are made.

  • During clinical trials, the most common injection-site reaction was pain (37%); the most common solicited systemic adverse reactions were headache (15%), fatigue (15%) and muscle pain (11%).

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Live, Attenuated Influenza Vaccine (LAIV)

FluMist (LAIV) is administered as an intranasal vaccine. LAIV vaccine is a quadrivalent vaccine (protects against four types of flu viruses). It is indicated for use in individuals 2 to 49 years of age. LAIV contains attenuated viruses and cannot cause influenza.

Studies support the safety of LAIV. In clinical trials, quadrivalent LAIV had a safety profile similar to the previously used trivalent LAIV, with the exception of slightly more reports of fever after the first dose of quadrivalent LAIV compared to trivalent LAIV. This occurred in a subset of children 2 years through 8 years of age who were getting vaccinated for the first time. Rhinitis (runny nose) and nasal congestion[1.1 MB, 26 pages] occur more commonly after LAIV than IIV or placebo in adults and children.

  • The most common adverse reactions to LAIV[1.1 MB, 26 pages] are runny nose or nasal congestion in all ages, fever >100°F in children 2-6 years of age, and sore throat in adults.
  • One study of 8,352 children aged 6 through 59 months showed that younger children aged 6 through 23 months (an age group for which LAIV is not licensed) had increased rates of wheezing in the 42 days after LAIV (6%) than after IIV (4%). Children aged 24 through 59 months had similar rates of wheezing after LAIV (2%)[1.1 MB, 26 pages] and IIV (3%).
  • According to the LAIV package insert:
    • In children aged 2 through 6 years, fever >100° F occurred more often after first dose LAIV (16%) than placebo (11%). Adults receiving LAIV did not have an increased risk for fever after vaccination compared with placebo.
    • In adults the following other adverse events were reported more often after LAIV than after an intranasal placebo: headache, sore throat, tiredness/weakness, muscles aches, cough, chills, and sinusitis.

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Reporting Adverse Events

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The National Vaccine Injury Compensation Program

The National Vaccine Injury Compensation Program (VICP) is a federal program that was created to compensate people who may have been injured by certain vaccines.

Individuals who believe they may have been injured by a vaccine can learn about the program and about filing a claim by calling 1-800-338-2382 or visiting the VICP website. There is a time limit to file a claim for compensation.

Special Consideration Regarding Egg Allergy

The recommendations for vaccination of people with egg allergies have not changed since last season (2016-2017).

People with egg allergies can receive any licensed, recommended age-appropriate influenza vaccine and no longer have to be monitored for 30 minutes after receiving the vaccine. People who have severe egg allergies should be vaccinated in a medical setting and be supervised by a health care provider who is able to recognize and manage severe allergic conditions.

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