Introduction

Recombinant influenza vaccine. Seasonal influenza vaccine recombinant (RIV; RIV4) contains recombinant hemagglutinin (HA) proteins representing influenza virus types A and B likely to circulate in the US during the upcoming season and is used to stimulate active immunity to influenza strains contained in the vaccine.

Uses for Influenza Vaccine Recombinant

Prevention of Seasonal Influenza A and B Virus Infections

Prevention of seasonal influenza virus infection in adults ≥18 years of age.

Influenza is an acute viral infection; influenza viruses spread from person to person mainly through large-particle respiratory droplet transmission. In the US, annual epidemics of seasonal influenza occur, usually during the fall or winter. Influenza viruses can cause illness in any age group; children have highest rate of infection. Influenza can exacerbate underlying medical conditions or lead to pneumonia in certain individuals. Adults ≥65 years of age, children <2 years of age, and individuals with chronic medical conditions have highest risk of influenza-related complications and death.

Annual vaccination is the primary means of preventing seasonal influenza and its complications. Annual influenza vaccination necessary since immunity declines in the year following vaccination and circulating influenza strains change from year to year.

CDC Advisory Committee on Immunization Practices (ACIP), AAP, and others recommend routine influenza vaccination for all individuals ≥6 months of age using an age-appropriate seasonal influenza vaccine, unless contraindicated. Vaccination against seasonal influenza recommended for otherwise healthy individuals as well as those who have medical conditions that put them at increased risk for influenza-related complications or at higher risk for influenza-related outpatient, emergency department, or hospital visits.

Several different types of influenza virus vaccines are commercially available in the US for active immunization against seasonal influenza, including an inactivated virus vaccine (influenza virus vaccine inactivated [IIV]), an adjuvanted inactivated virus vaccine (influenza vaccine, adjuvanted [aIIV]), a recombinant vaccine (influenza vaccine recombinant [RIV]), and a live attenuated virus vaccine (influenza vaccine live intranasal [LAIV]). The various vaccine formulations also differ based on method of manufacturer (egg-based versus cell culture-based), dose (standard versus high-dose), and route of administration (e.g., parenteral versus intranasal),

Select specific influenza vaccine based on age and health status of the individual. For many individuals, more than one type of influenza vaccine may be appropriate.

ACIP and AAP state that there are no preferential recommendations for any specific vaccine type or trade name when more than one licensed, recommended, and age-appropriate vaccine is available, with the exception of selection of influenza vaccines for individuals ≥65 years of age. If an age-appropriate vaccine is available and there are no contraindications, do not delay vaccination to obtain a specific product.

Seasonal influenza vaccines are not effective against all possible strains of influenza, but may be effective against influenza strains (and possibly closely related strains) represented in the vaccines. (See Limitations of Vaccine Effectiveness under Cautions.)

Current information regarding influenza surveillance and updated recommendations for prevention and treatment of seasonal influenza is available from CDC at [Web].

Influenza Vaccination During the Coronavirus Disease 2019 (COVID-19) Pandemic

CDC and ACIP state that efforts to ensure influenza vaccination for all individuals ≥6 months of age for the upcoming (current) influenza season are of paramount importance to reduce influenza-related morbidity and mortality and reduce the impact of respiratory illnesses in the population and the resulting burdens on the health-care system. SARS-CoV-2 (causative agent of COVID-19) is expected to circulate in the US during the influenza season; the extent of continued or recurrent SARS-CoV-2 circulation during the time influenza viruses are circulating is not known. Vaccination against influenza can reduce prevalence of influenza illness and reduce incidence of influenza symptoms that might be confused with COVID-19 symptoms (i.e., fever, cough, dyspnea). In addition, prevention of influenza and reduction in severity of influenza illness and associated outpatient visits, hospitalizations, and intensive care unit admissions could alleviate stress on the US health-care system.

ACIP recommends that influenza vaccination should be deferred in symptomatic individuals with moderate or severe COVID-19 until recovery and deferral also may be considered in persons with mild or asymptomatic COVID-19 illness. (See Individuals with Known or Suspected Coronavirus Disease 2019 [COVID-19] under Cautions.)

Influenza Vaccine Recombinant Dosage and Administration

General

Administer seasonal influenza vaccine every year before exposure to seasonal influenza. In the US, localized outbreaks indicating start of annual influenza season can occur as early as October and peak influenza activity (which often is close to the midpoint of influenza activity for the season) usually occurs in January or February or later.

ACIP recommends offering influenza vaccination by the end of October, if possible, and continuing to offer vaccination as long as influenza viruses are circulating and unexpired vaccine is available. Although influenza vaccination by the end of October is recommended, vaccination in December or later (even if influenza activity has begun) is likely to be beneficial in the majority of influenza seasons.

There is evidence that early influenza vaccination (i.e., in July or August) in individuals requiring only a single dose of influenza vaccine is likely to be associated with suboptimal immunity (waning immunity) before the end of influenza season, particularly in older adults. Community vaccination programs should balance maximizing likelihood of persistence of vaccine-induced protection through the influenza season with avoiding missed opportunities for vaccination or vaccinating after influenza circulation has already started.

Administration

Administer only by IM injection. Do not administer sub-Q, intradermally, or IV.

Syncope (vasovagal or vasodepressor reaction; fainting) may occur following vaccination; such reactions occur most frequently in adolescents and young adults. Take appropriate measures to decrease risk of injury if patient becomes weak or dizzy or loses consciousness (e.g., have vaccinees sit or lie down during and for 15 minutes after vaccination). If syncope occurs, observe patient until symptoms resolve.

May be given simultaneously with other age-appropriate vaccines. When multiple vaccines administered during a single health-care visit, give each parenteral vaccine using separate syringes and different injection sites. Separate injection sites by ≥1 inch (if anatomically feasible) to allow appropriate attribution of any local adverse effects that may occur.

IM Administration

Administer by IM injection preferably into the deltoid muscle in adults.

To ensure delivery into muscle, make IM injections at a 90° angle to the skin using a needle length appropriate for the individual’s age and body mass, thickness of adipose tissue and muscle at injection site, and injection technique.

Vaccine should appear clear and colorless; do not use if it appears discolored or contains particles.

Gently invert single-dose prefilled syringes of the vaccine prior to affixing appropriate size needle.

Do not mix with any other vaccine or solution.

Dosage

Adults

Prevention of Seasonal Influenza A and B Virus Infections

Adults ≥18 Years of Age

Single 0.5-mL dose.

Special Populations

Hepatic Impairment

No specific dosage recommendations.

Renal Impairment

No specific dosage recommendations.

Geriatric Patients

Single 0.5-mL dose. (See Geriatric Use under Cautions.)

Contraindications

• History of severe allergic reaction (e.g., anaphylaxis) to any component of the vaccine.

• History of severe allergic reactions (e.g., anaphylaxis) to a previous dose of any recombinant influenza vaccine (quadrivalent or trivalent formulation).

Warnings/Precautions

Sensitivity Reactions

Anaphylaxis, anaphylactoid reactions, allergic reactions, and other forms of hypersensitivity reported during postmarketing experience.

Prior to administration, review patient’s history with respect to possible sensitivity reactions to the vaccine or vaccine components and prior vaccination-related adverse effects and assess benefits versus risks. Appropriate medical treatment and supervision must be available for immediate use in case an anaphylactic reaction occurs.

ACIP states that a history of severe allergic reaction (e.g., anaphylaxis) to any other type of influenza vaccine (egg-based influenza virus vaccine inactivated, cell culture-based influenza vaccine inactivated, influenza vaccine live intranasal) is a precaution to use of influenza vaccine recombinant. If influenza vaccine recombinant used in an individual with such a history, administer the vaccine in an inpatient or outpatient medical setting supervised by a health-care provider able to recognize and manage severe allergic reactions. Consider consultation with an allergist to help identify the vaccine component responsible for the prior reaction.

Guillain-Barré Syndrome (GBS)

If GBS occurred within 6 weeks after previous influenza vaccination, manufacturer states base decision to administer influenza vaccine recombinant on careful consideration of potential benefits and risks.

The 1976 swine influenza vaccine was associated with increased frequency of GBS. Evidence for causal relationship between other influenza vaccines and GBS inconclusive; if an excess risk exists, it probably is slightly more than 1 additional case of GBS per 1 million vaccinees.

ACIP states that, as a precaution, individuals who are not at higher risk for severe influenza complications and who developed GBS within 6 weeks of a previous dose of influenza vaccine generally should not receive influenza vaccination; clinicians might consider use of antiviral prophylaxis for such individuals. However, ACIP states that benefits of influenza vaccine may outweigh risks for certain individuals with a history of GBS within 6 weeks after a previous dose of influenza vaccine who are at higher risk for severe complications from influenza.

Individuals with Altered Immunocompetence

May be administered to individuals immunosuppressed as the result of disease or immunosuppressive therapy. Consider possibility that immune response to the vaccine and efficacy may be reduced in such individuals.

ACIP states that recombinant vaccines can be administered safely to individuals with altered immunocompetence.

Individuals with Bleeding Disorders

Advise individuals who have bleeding disorders or are receiving anticoagulant therapy and/or their family members about the risk of hematoma from IM injections.

ACIP states that IM vaccines may be given to individuals who have bleeding disorders or are receiving anticoagulant therapy if a clinician familiar with the patient’s bleeding risk determines that the IM injection can be administered with reasonable safety. In these cases, use a fine needle (23 gauge or smaller) to administer the vaccine and apply firm pressure to injection site (without rubbing) for ≥2 minutes. In individuals receiving therapy for hemophilia, give IM vaccine shortly after a scheduled dose of such therapy.

Concomitant Illness

Base decision to administer or delay vaccination in an individual with a current or recent acute illness on severity of symptoms and etiology of the illness.

ACIP states mild acute illness generally does not preclude vaccination.

ACIP states moderate or severe acute illness (with or without fever) is a precaution for vaccination; defer vaccines until individual has recovered from the acute phase of the illness. This avoids superimposing vaccine adverse effects on the underlying illness or mistakenly concluding that a manifestation of the underlying illness resulted from vaccine administration.

Individuals with Known or Suspected Coronavirus Disease 2019 (COVID-19)

ACIP states defer routine vaccinations, including influenza vaccination, in symptomatic individuals with suspected or confirmed COVID-19 until criteria for discontinuance of COVID-19 isolation have been met and the individual is no longer moderately or severely ill. Consider deferring vaccination until the individual has fully recovered from the acute illness to avoid exposing health-care personnel and other patients to the disease. ACIP also states that routine vaccinations, including influenza vaccination, should be deferred in patients with mild or asymptomatic COVID-19 to avoid the inability to discern between COVID-19 symptoms and postvaccination reactions. Other considerations include the presence of risk factors for severe influenza illness and the likelihood of being able to vaccinate at a later date.

Limitations of Vaccine Effectiveness

Following seasonal influenza vaccination, up to 2 weeks may be required to develop antibody protection against infection.

May not protect all vaccine recipients from influenza.

Seasonal influenza vaccines are formulated annually to contain influenza A and B antigens predicted to represent strains of influenza virus likely to circulate in the US during the upcoming influenza season. (See Actions.) Efficacy of seasonal influenza vaccine during any given year depends on how closely viral strains represented in the vaccine match viral strains circulating during the season.

Seasonal influenza vaccines not expected to provide protection against human infection with animal-origin influenza viruses, including avian influenza A viruses (e.g., avian influenza A [H5N1], avian influenza A [H7N9]).

Seasonal influenza vaccines will not provide protection against COVID-19.

Duration of Immunity

Immunity declines during the year after seasonal influenza vaccination. In addition, circulating strains of seasonal influenza virus change from year to year. Annual vaccination is needed for prevention of seasonal influenza.

Do not administer influenza vaccine from a previous influenza season in an attempt to provide protection during a subsequent influenza season.

Improper Storage and Handling

Improper storage or handling of vaccines may reduce vaccine potency resulting in reduced or inadequate immune response in vaccinees.

Inspect all vaccines upon delivery and monitor during storage to ensure that the appropriate temperature is maintained. (See Storage under Stability.)

Do not administer vaccine that has been mishandled or has not been stored at the recommended temperature.

If there are concerns about mishandling, contact the manufacturer or state or local immunization or health departments for guidance on whether the vaccine is usable; also can consult CDC.

Specific Populations

Pregnancy

Manufacturer states data insufficient to assess risk of influenza vaccine recombinant in pregnant women.

Pregnant and postpartum women are at higher risk for severe influenza and complications from influenza, particularly during second and third trimesters.

ACIP, ACOG, AAP, and others recommend vaccination against influenza in all women who are pregnant or who might become pregnant during the influenza season and state that any licensed, age-appropriate, inactivated influenza vaccine (i.e., influenza virus vaccine inactivated or influenza vaccine recombinant) can be used. These experts state that inactivated influenza vaccines can be administered at any time during pregnancy before or during influenza season. Encourage postpartum women who did not receive influenza vaccination during pregnancy to receive vaccination (e.g., before hospital discharge).

Pregnancy registry at 800-822-2463. Clinicians or vaccinees should report any exposure to the vaccine that occurs during pregnancy.

Lactation

Not known whether influenza vaccine recombinant is distributed into milk. Data insufficient to assess effects on breast-fed infant or on milk production.

Consider benefits of breast-feeding and importance of the vaccine to the woman; also consider potential adverse effects on the breast-fed child from the vaccine or underlying maternal condition (i.e., susceptibility to influenza infection).

ACIP states recombinant vaccines do not pose any unusual risks for women who are breast-feeding or their breast-fed infants.

Pediatric Use

Safety and efficacy not established in individuals <18 years of age.

Study using trivalent influenza vaccine recombinant (no longer available in US) indicates recombinant vaccine may not be effective in children <3 years of age^{† [off-label]}.

Geriatric Use

Insufficient experience using influenza vaccine recombinant in adults ≥65 years of age to determine whether geriatric patients respond differently than younger adults.

ACIP states use influenza virus vaccine inactivated or influenza vaccine recombinant in adults ≥65 years of age. ACIP states a preference for Fluzone High-Dose (quadrivalent), Flublok recombinant influenza vaccine (quadrivalent), or the standard-dose quadrivalent adjuvant-containing vaccine (Fluad), but if none of these 3 vaccines are available at the time of vaccine administration, then they state that adults ≥65 years may receive a standard-dose quadrivalent preparation.

Common Adverse Effects

Adults ≥18 years of age: Injection site reactions (e.g., local tenderness, pain), headache, fatigue, myalgia, arthralgia.

General

Administer seasonal influenza vaccine every year before exposure to seasonal influenza. In the US, localized outbreaks indicating start of annual influenza season can occur as early as October and peak influenza activity (which often is close to the midpoint of influenza activity for the season) usually occurs in January or February or later.

ACIP recommends offering influenza vaccination by the end of October, if possible, and continuing to offer vaccination as long as influenza viruses are circulating and unexpired vaccine is available. Although influenza vaccination by the end of October is recommended, vaccination in December or later (even if influenza activity has begun) is likely to be beneficial in the majority of influenza seasons.

There is evidence that early influenza vaccination (i.e., in July or August) in individuals requiring only a single dose of influenza vaccine is likely to be associated with suboptimal immunity (waning immunity) before the end of influenza season, particularly in older adults. Community vaccination programs should balance maximizing likelihood of persistence of vaccine-induced protection through the influenza season with avoiding missed opportunities for vaccination or vaccinating after influenza circulation has already started.

Administration

Administer only by IM injection. Do not administer sub-Q, intradermally, or IV.

Syncope (vasovagal or vasodepressor reaction; fainting) may occur following vaccination; such reactions occur most frequently in adolescents and young adults. Take appropriate measures to decrease risk of injury if patient becomes weak or dizzy or loses consciousness (e.g., have vaccinees sit or lie down during and for 15 minutes after vaccination). If syncope occurs, observe patient until symptoms resolve.

May be given simultaneously with other age-appropriate vaccines. When multiple vaccines administered during a single health-care visit, give each parenteral vaccine using separate syringes and different injection sites. Separate injection sites by ≥1 inch (if anatomically feasible) to allow appropriate attribution of any local adverse effects that may occur.

IM Administration

Administer by IM injection preferably into the deltoid muscle in adults.

To ensure delivery into muscle, make IM injections at a 90° angle to the skin using a needle length appropriate for the individual’s age and body mass, thickness of adipose tissue and muscle at injection site, and injection technique.

Vaccine should appear clear and colorless; do not use if it appears discolored or contains particles.

Gently invert single-dose prefilled syringes of the vaccine prior to affixing appropriate size needle.

Do not mix with any other vaccine or solution.

Dosage

Adults

Prevention of Seasonal Influenza A and B Virus Infections

Adults ≥18 Years of Age

Single 0.5-mL dose.

Special Populations

Hepatic Impairment

No specific dosage recommendations.

Renal Impairment

No specific dosage recommendations.

Geriatric Patients

Single 0.5-mL dose. (See Geriatric Use under Cautions.)

Immunosuppressive Agents

Immune responses to vaccines may be reduced in individuals receiving immunosuppressive agents.

Generally, give inactivated vaccines ≥2 weeks prior to initiation of immunosuppressive therapy and, because of possible suboptimal response, do not give during and for certain periods of time after immunosuppressive therapy discontinued.

Time to restoration of immune competence varies depending on type and intensity of immunosuppressive therapy, underlying disease, and other factors; optimal timing for vaccine administration after discontinuance of immunosuppressive therapy not identified for every situation.

Vaccines

Although specific studies may not be available, ACIP states influenza vaccine recombinant may be administered concurrently or sequentially with other age-appropriate vaccines, including live virus vaccines, toxoids, or inactivated or recombinant vaccines.

Specific Drugs