Prevention and Control of Seasonal Influenza with Vaccines ... - CDC

Recommendations for the Use of Influenza Vaccines, 2023–24

Groups Recommended for Vaccination

Routine annual influenza vaccination of all persons aged ≥6 months who do not have contraindications continues to be recommended. Influenza vaccines expected to be available for the 2023–24 season, their age indications, and their presentations are described (Table 1). Available influenza vaccines and age indications are expected to be similar to those of the 2022–23 season. Recommendations regarding timing of vaccination, considerations for specific populations, the use of specific vaccines, and contraindications and precautions are summarized in the sections that follow.

Timing of Vaccination

Because timing of the onset, peak, and decline of influenza activity varies the ideal time to start vaccinating cannot be predicted each season. Decisions about timing necessitate balancing considerations regarding this unpredictability of the influenza season, possible waning of vaccine-induced immunity over the course of a season, and programmatic considerations. For most persons who need only 1 dose of influenza vaccine for the season, vaccination should ideally be offered during September or October. However, vaccination should continue after October and throughout the influenza season as long as influenza viruses are circulating and unexpired vaccine is available.

Influenza vaccines might be available as early as July or August; however, vaccination during these months is not recommended for most groups because of the possible waning of immunity over the course of the influenza season (21–37). However, vaccination of such persons during July and August can be considered in instances where there is concern that the recipient will not be vaccinated at a later date. Considerations for timing of vaccination include the following:

• For most adults (particularly adults aged ≥65 years) and for pregnant persons in the first or second trimester: Vaccination during July and August should be avoided unless there is concern that vaccination later in the season might not be possible.
• Children who require 2 doses: Certain children aged 6 months through 8 years require 2 doses of influenza vaccine for the season (see Children Aged 6 Months Through 8 Years: Number of Influenza Vaccine Doses) (Figure). These children should receive their first dose as soon as possible (including during July and August, if vaccine is available) to allow the second dose (which must be administered ≥4 weeks later) to be received, ideally, by the end of October.
• Children who require only 1 dose: Vaccination during July and August can be considered for children of any age who need only 1 dose of influenza vaccine for the season. Although waning of immunity after vaccination over the course of the season has been observed among all age groups (21–37), there are fewer published studies reporting results specifically among children (21,30,32,33,37). Moreover, children in this group might visit health care providers during the late summer months for medical examinations before the start of school. Vaccination can be considered at this time because it represents a vaccination opportunity.
• Pregnant persons in the third trimester: Vaccination during July and August can be considered for pregnant persons who are in the third trimester during these months because vaccination has been associated in multiple studies with reduced risk for influenza illness in their infants during the first months after birth, when they are too young to receive influenza vaccine (38–41). For pregnant persons in the first or second trimester during July and August, waiting to vaccinate until September or October is preferable, unless there is concern that later vaccination might not be possible.

Community vaccination programs should balance maximizing the likelihood of persistence of vaccine-induced protection through the season with avoiding missed opportunities to vaccinate or vaccinating after onset of influenza circulation occurs. Efforts should be structured to optimize vaccination coverage before influenza activity in the community begins. Vaccination should continue to be offered as long as influenza viruses are circulating and unexpired vaccine is available. To avoid missed opportunities for vaccination, providers should offer vaccination during routine health care visits and hospitalizations. No recommendation is made for revaccination (i.e., providing a booster dose) later in the season of persons who have been fully vaccinated for the season, regardless of when the current season vaccine was received.

Optimally, vaccination should occur before onset of influenza activity in the community. However, because timing of the onset, peak, and decline of influenza activity varies, the ideal time to start vaccinating cannot be predicted each season. Moreover, more than one outbreak might occur in a community in a single season. In the United States, localized outbreaks indicating the start of seasonal influenza activity can occur as early as October. However, in 30 (77%) of 39 influenza seasons from 1982–83 through 2021–22, peak influenza activity did not occur until January or later, and in 24 (62%) seasons, the peak was in February or later (42). Activity peaked in February in 17 (44%) of these seasons (42).

An increasing number of observational studies (21–37) have reported decreases in vaccine effectiveness with increasing time postvaccination within a single influenza season. Waning effects have not been observed consistently across age groups, influenza viruses (types, subtypes, and lineages), or seasons. Certain studies suggest waning occurs to a greater degree against influenza A(H3N2) viruses than against influenza A(H1N1) or influenza B viruses (25,31,35). This effect also might vary with recipient age; in certain studies, waning was more pronounced among older adults (21,22,24,31,34) and younger children (21). Relatively fewer reports include results specific to children (21,30,32,33,37); findings suggestive of waning have been reported in certain studies (21,32,33,37) but not others (30). Rates of decline in vaccine effectiveness also varied. A multiseason (2011–12 through 2014–15) analysis from the U.S. Influenza Vaccine Effectiveness (U.S. Flu VE) Network found that vaccine effectiveness decreased by approximately 7% per month for influenza A(H3N2) and influenza B and 6%–11% per month for influenza A(H1N1)pdm09 (23). A prospective test-negative case control study of the 2015–16 through 2019–20 seasons observed an average decline in vaccine effectiveness against influenza-associated hospitalizations of 1.3% per month among children aged ≤8 years and 4.7% per month among those aged 9 through 17 years (37). In the Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN) during the 2015–16 through 2018–19 seasons, vaccine effectiveness against influenza-associated hospitalizations declined by approximately 8%–9% per month for all adults and approximately 10%–11% per month for those aged ≥65 years (24). An analysis of the 2010–11 through 2013–14 seasons noted estimated effectiveness ranging from 54% to 67% during days 0–180 postvaccination; estimated vaccine effectiveness was not significant during the period between days 181 and 365 (32). A multiseason analysis (2010–11 through 2014–15) conducted in Europe noted a decline in vaccine effectiveness to 0% at 111 days postvaccination against influenza A(H3N2) viruses. Vaccine effectiveness against influenza B viruses decreased more slowly, and vaccine effectiveness against influenza A(H1N1)pdm09 viruses remained roughly stable at 50%–55% throughout the influenza season (25). A meta-analysis of 14 studies examining waning of influenza vaccine effectiveness using the test-negative design found a significant decline in effectiveness within 180 days after vaccination against influenza A(H3N2) and influenza B but not against influenza A(H1N1) (43). In addition to the factors observed to be associated with waning immunity across studies, observed decreases in protection might be at least in part attributable to bias, unmeasured confounding, or the late-season emergence of antigenic drift variants of influenza viruses that are less well-matched to the vaccine viruses.

Varying data concerning the presence and rate of waning immunity after influenza vaccination, coupled with the unpredictable timing of the influenza season each year, prevent determination of an optimal time to vaccinate each season. Programmatic issues also are a consideration. Although delaying vaccination might result in greater immunity later in the season, deferral also might result in missed opportunities to vaccinate as well as difficulties in vaccinating a population within a more constrained period. The potential contributions of these factors among persons aged ≥65 years have been assessed using a simulated mathematical model examining various scenarios of vaccination timing, timing of onset of the influenza season, vaccine effectiveness, and rate of waning (44). In this model, during an influenza season beginning in October and peaking in January, delaying vaccination until October resulted in more hospitalizations if >14% of persons aged ≥65 years who would have been vaccinated in August or September did not get vaccinated. However, these predictions varied considerably with assumed timing of season onset, rate of waning immunity, and vaccine effectiveness.

Vaccination efforts should continue throughout the season because the duration of the influenza season varies, and influenza activity might not occur in certain communities until February, March, or later (17). Providers should offer influenza vaccine at healthcare visits to those not yet vaccinated, and organized vaccination campaigns should continue throughout the influenza season, including after influenza activity has begun in the community. Although vaccination by the end of October is recommended, vaccine administered in December or later, even if influenza activity has already begun, might be beneficial in most influenza seasons. Providers should offer influenza vaccination to unvaccinated persons who have already become ill with influenza during the season because the vaccine might protect them against other circulating influenza viruses.

Guidance for Influenza Vaccination in Specific Populations and Situations

Populations at Higher Risk for Medical Complications Attributable to Severe Influenza

All persons aged ≥6 months who do not have contraindications should be vaccinated annually. However, vaccination to prevent influenza is particularly important for persons who are at increased risk for severe illness and complications from influenza and for influenza-related outpatient, emergency department, or hospital visits. When vaccine supply is limited, vaccination efforts should focus on vaccination of persons at higher risk for medical complications attributable to severe influenza who do not have contraindications. These persons include the following (order of listing does not imply hierarchy or prioritization among these populations):

• All children aged 6 through 59 months.
• All persons aged ≥50 years.
• Adults and children who have chronic pulmonary (including asthma), cardiovascular (excluding isolated hypertension), renal, hepatic, neurologic, hematologic, or metabolic disorders (including diabetes mellitus).
• Persons who are immunocompromised due to any cause (including but not limited to immunosuppression caused by medications or HIV infection).
• Persons who are or will be pregnant during the influenza season.
• Children and adolescents (aged 6 months through 18 years) who are receiving aspirin- or salicylate-containing medications and who might be at risk for experiencing Reye syndrome after influenza virus infection.
• Residents of nursing homes and other long-term care facilities.
• American Indian or Alaska Native persons.
• Persons who are extremely obese (body mass index ≥40 for adults).

An age-appropriate IIV4 or RIV4 is suitable for all persons recommended for vaccination, including those in the risk groups listed. LAIV4 is not recommended for certain populations, including certain of these listed groups. Contraindications and precautions for the use of LAIV4 are noted (Table 2).

Persons Who Live with or Care for Persons at Higher Risk for Influenza-Related Complications

All persons aged ≥6 months without contraindications should be vaccinated annually. However, emphasis also should be placed on vaccination of persons who live with or care for those who are at increased risk for medical complications attributable to severe influenza. When vaccine supply is limited, vaccination efforts should focus on administering vaccination to persons at higher risk for influenza-related complications as well as persons who live with or care for such persons, including the following:

• Health care personnel, including all paid and unpaid persons working in health care settings who have the potential for exposure to patients or to infectious materials. These personnel might include but are not limited to physicians, nurses, nursing assistants, nurse practitioners, physician assistants, therapists, technicians, emergency medical service personnel, dental personnel, pharmacists, laboratory personnel, autopsy personnel, students and trainees, contractual staff members, and others not directly involved in patient care but who might be exposed to infectious agents (e.g., clerical, dietary, housekeeping, laundry, security, maintenance, administrative, and billing staff members and volunteers). ACIP guidance for vaccination of health care personnel has been published previously (45).
• Household contacts (including children aged ≥6 months) and caregivers of children aged ≤59 months (<5 years) and adults aged ≥50 years, particularly contacts of children aged <6 months.
• Household contacts (including children aged ≥6 months) and caregivers of persons with medical conditions that put them at higher risk for severe complications from influenza.

Health care personnel and persons who are contacts of persons in these groups (with the exception of contacts of severely immunocompromised persons who require a protected environment) may receive any influenza vaccine that is otherwise indicated. Persons who care for severely immunocompromised persons requiring a protected environment should not receive LAIV4. ACIP and the Healthcare Infection Control Practices Advisory Committee (HICPAC) have previously recommended that health care personnel who receive LAIV should avoid providing care for severely immunocompromised persons requiring a protected environment for 7 days after vaccination and that hospital visitors who have received LAIV should avoid contact with such persons for 7 days after vaccination (46). However, such persons need not be restricted from caring for or visiting less severely immunocompromised persons.

Influenza Vaccination of Persons with COVID-19

Specific data concerning the optimal timing of influenza vaccination of persons with COVID-19 illness are not available. For those who have moderate or severe COVID-19, vaccination should usually be deferred until they have recovered from the acute illness, consistent with General Best Practice Guidelines for Immunization (47). For those with mild or asymptomatic COVID-19, further deferral might be considered to avoid confusing COVID-19 symptoms with potential postvaccination reactions. Other considerations for determination of when to vaccinate include current local influenza activity, the recipient's individual risk for severe influenza illness, current or recent use of immunosuppressive therapeutic agents that might blunt immune response to vaccines, and risk for exposing others in the vaccination setting to COVID-19. Information concerning precautions for persons with COVID-19 is available at https://www.cdc.gov/coronavirus/2019-ncov/hcp/duration-isolation.html.

Children Aged 6 Through 35 Months: Influenza Vaccine Dose Volumes

Five IIV4s are approved for children aged ≥6 months (Table 1). Four of these vaccines are egg based (Afluria Quadrivalent, Fluarix Quadrivalent, FluLaval Quadrivalent, and Fluzone Quadrivalent), and one is cell culture–based (Flucelvax Quadrivalent). For these vaccines, the approved dose volumes for children aged 6 through 35 months are as follows (Table 4):

• Afluria Quadrivalent: 0.25 mL per dose. However, 0.25-mL prefilled syringes are no longer available. For children aged 6 through 35 months, a 0.25-mL dose must be obtained from a multidose vial (48).
• Fluarix Quadrivalent: 0.5 mL per dose (49).
• Flucelvax Quadrivalent: 0.5 mL per dose (50).
• FluLaval Quadrivalent: 0.5 mL per dose (51).
• Fluzone Quadrivalent: Either 0.25 mL or 0.5 mL per dose. Per the package insert, each dose may be given at either volume (52); however, 0.25-mL prefilled syringes are no longer available.

For all of these IIV4s, persons aged ≥36 months (≥3 years) should receive 0.5 mL per dose. Alternatively, healthy children aged ≥24 months (≥2 years) can receive LAIV4, 0.2 mL intranasally (0.1 mL in each nostril) (53). LAIV4 is not recommended for certain populations and is not approved for children aged <2 years or adults >49 years (see Contraindications and Precautions for the Use of LAIV4) (Table 2). RIV4 is not approved for children aged <18 years (54). High-dose inactivated influenza vaccine (HD-IIV4) (55) and adjuvanted inactivated influenza vaccine (aIIV4) (56) are not approved for persons aged <65 years.

Care should be taken to administer an age-appropriate vaccine at the appropriate volume for each dose. For IIV4s, the recommended volume may be administered from a prefilled syringe containing the appropriate volume (as supplied by the manufacturer), a single-dose vial, or a multidose vial. Single-dose vials should be used for only 1 dose, and multidose vials should be used only for the maximum number of doses specified in the package insert. Any vaccine remaining in a vial after the maximum number of doses has been removed should be discarded, regardless of the volume of the doses obtained or any remaining volume in the vial.

Children Aged 6 Months Through 8 Years: Number of Influenza Vaccine Doses

Children aged 6 months through 8 years require 2 doses of influenza vaccine administered a minimum of 4 weeks apart during their first season of vaccination for optimal protection (57–60). Determination of the number of doses needed is based on 1) the child's age at the time of the first dose of 2023–24 influenza vaccine and 2) the number of doses of influenza vaccine received in previous influenza seasons.

• For children aged 6 months through 8 years, the number of doses of influenza vaccine needed for the 2023–24 influenza season is determined as follows (Figure):
  • Those who have previously received ≥2 total doses of trivalent or quadrivalent influenza vaccine ≥4 weeks apart before July 1, 2023, require only 1 dose for the 2023–24 season. The previous 2 doses of influenza vaccine do not need to have been received in the same season or consecutive seasons.
  • Those who have not previously received ≥2 doses of trivalent or quadrivalent influenza vaccine ≥4 weeks apart before July 1, 2023, or whose previous influenza vaccination history is unknown, require 2 doses for the 2023–24 season. The interval between the 2 doses should be ≥4 weeks. Children aged 6 months through 8 years who require 2 doses of influenza vaccine should receive their first dose as soon as possible (including during July and August, if vaccine is available) to allow the second dose (which must be administered ≥4 weeks later) to be received, ideally, by the end of October. For children aged 8 years who require 2 doses of vaccine, both doses should be administered even if the child turns age 9 years between receipt of dose 1 and dose 2.
• Adults and children aged ≥9 years need only 1 dose of influenza vaccine for the 2023–24 season.

Pregnant Persons

Pregnant and postpartum persons have been observed to be at higher risk for severe illness and complications from influenza, particularly during the second and third trimesters. Influenza vaccination during pregnancy is associated with reduced risk for respiratory illness and influenza among pregnant and postpartum persons as well as infants during the first months of life (38–41,61). ACIP and the American College of Obstetricians and Gynecologists recommend that persons who are pregnant or who might be pregnant or postpartum during the influenza season receive influenza vaccine (62). Any licensed, recommended, and age-appropriate IIV4 or RIV4 may be used. LAIV4 should not be used during pregnancy but can be used postpartum. Influenza vaccine can be administered at any time during pregnancy (i.e., during any trimester), before and during the influenza season. Early vaccination (i.e., during July and August) can be considered for persons who are in the third trimester during these months if vaccine is available because this can provide protection for the infant during the first months of life when they are too young to be vaccinated (38–41,61).

Although experience with the use of IIVs during pregnancy is substantial, data specifically reflecting administration of influenza vaccines during the first trimester are limited. Most studies have not noted an association between influenza vaccination and adverse pregnancy outcomes, including spontaneous abortion (miscarriage) (63–73). One observational Vaccine Safety Datalink (VSD) study conducted during the 2010–11 and 2011–12 seasons noted an association between receipt of IIV containing influenza A(H1N1)pdm09 and risk for miscarriage in the 28 days after receipt of IIV, when an H1N1pdm09-containing vaccine also had been received the previous season (74). However, in a larger VSD follow-up study, IIV was not associated with an increased risk for miscarriage during the 2012–13, 2013–14, and 2014–15 seasons, regardless of previous season vaccination (75).

There is less experience with the use of more recently licensed influenza vaccines (e.g., quadrivalent, cell culture-based, and recombinant vaccines) during pregnancy compared with previously available products. For ccIIV, a review of Vaccine Adverse Event Reporting System (VAERS) reports from 2013 through 2020 (76) and a prospective cohort study conducted from 2017 through 2020 (77) did not reveal unexpected safety events among pregnant persons. Data from a randomized clinical trial conducted at Clinical Immunization Safety Assessment (CISA) Project sites comparing the safety of RIV4 versus IIV4 in 382 pregnant persons supported the safety of RIV4 in pregnancy (78). Pregnancy registries and surveillance studies exist for certain products, for which information can be found in package inserts.

Older Adults

ACIP recommends that adults aged ≥65 years preferentially receive any one of the following higher dose or adjuvanted influenza vaccines: quadrivalent high-dose inactivated influenza vaccine (HD-IIV4), quadrivalent recombinant influenza vaccine (RIV4), or quadrivalent adjuvanted inactivated influenza vaccine (aIIV4). If none of these three vaccines is available at an opportunity for vaccine administration, then any other age-appropriate influenza vaccine should be administered (79,80).

Older adults (aged ≥65 years) are at increased risk for severe influenza-associated illness, hospitalization, and death compared with younger persons (4,17,81). Influenza vaccines are often less effective in this population (82). HD-IIV, RIV, and aIIV have been evaluated in comparison with nonadjuvanted SD-IIVs in this age group. Two of these vaccines, HD-IIV and RIV, are higher dose vaccines, which contain an increased dose of HA antigen per virus compared with nonadjuvanted SD-IIVs (60 μg for HD-IIV4 and 45 μg for RIV4, compared with 15 μg for standard-dose inactivated vaccines). The adjuvanted vaccine contains 15 μg of HA per virus, similarly to nonadjuvanted SD-IIVs, but contains the adjuvant MF59.

HD-IIV, RIV, and aIIV have shown relative benefit compared with SD-IIVs in certain studies, with the most evidence available for HD-IIV3. Randomized efficacy studies comparing these vaccines with nonadjuvanted SD-IIVs against laboratory-confirmed influenza outcomes are few in number (83–85) and cover few influenza seasons. Observational studies, predominantly retrospective cohort studies using diagnostic code–defined (rather than laboratory-confirmed) influenza outcomes, are more numerous and include more influenza seasons (86–96). Certain observational studies have reported relative benefit for HD-IIV, RIV, and aIIV in comparison with nonadjuvanted SD-IIVs, particularly in prevention of influenza-associated hospitalizations. The size of this relative benefit has varied from season to season and is not observed in all studies in all seasons, making it difficult to generalize the findings to all or most seasons. Studies directly comparing HD-IIV, RIV, and aIIV with one another are few and do not support a conclusion that any one of these vaccines is consistently superior to the others across seasons (86–88,91,97,98).

During the 2020–21 season, quadrivalent formulations of high-dose (HD-IIV4) and adjuvanted (aIIV4) influenza vaccines were introduced. Trivalent formulations of these vaccines are no longer available. Data summarizing comparisons of these newer quadrivalent formulations relative to nonadjuvanted SD-IIV4s are limited. In a pragmatic randomized open-label feasibility study of HD-IIV4 compared with SD-IIV4 conducted in Denmark among persons aged 65 through 79 years during the 2021–22 influenza season that collected data from health registries, HD-IIV4 was associated with lower risk for diagnostic code–defined pneumonia and influenza hospitalizations (relative vaccine effectiveness 64.4; 95% CI = 24.4–84.6) (99).

Immunocompromised Persons

ACIP recommends that persons with compromised immunity (including but not limited to persons with congenital and acquired immunodeficiency states, persons who are immunocompromised due to medications, and persons with anatomic and functional asplenia) should receive an age-appropriate IIV4 or RIV4. ACIP recommends that LAIV4 not be used for these groups because of the uncertain but biologically plausible risk for disease attributable to the live vaccine virus. Use of LAIV4 in persons with these and other conditions is discussed in more detail (see Dosage, Administration, Contraindications, and Precautions) (Table 2).

Immunocompromised states comprise a heterogeneous range of conditions with varying risks for severe infections. In many instances, limited data are available regarding the effectiveness of influenza vaccines in the setting of specific immunocompromised states (100). Timing of vaccination might be a consideration (e.g., vaccinating during a period either before or after an immunocompromising intervention). The Infectious Diseases Society of America has published detailed guidance for the selection and timing of vaccines for persons with specific immunocompromising conditions (101). Immune response to influenza vaccines might be blunted in persons with certain conditions, such as congenital immune deficiencies, and in persons receiving cancer chemotherapy, posttransplant regimens, or immunosuppressive medications.

Persons with a History of Guillain-Barré Syndrome After Influenza Vaccination

A history of Guillain-Barré syndrome (GBS) within 6 weeks of a previous dose of any type of influenza vaccine is considered a precaution for influenza vaccination (Table 2). Persons who are not at higher risk for severe influenza complications (see Populations at Higher Risk for Medical Complications Attributable to Severe Influenza) and who are known to have experienced GBS within 6 weeks of a previous influenza vaccination typically should not be vaccinated. As an alternative to vaccination, providers might consider using influenza antiviral chemoprophylaxis for these persons (102). However, the benefits of influenza vaccination might outweigh the possible risks for certain persons who have a history of GBS within 6 weeks after receipt of influenza vaccine and who also are at higher risk for severe complications from influenza.

Persons with a History of Egg Allergy

ACIP recommends that all persons aged ≥6 months with egg allergy should receive influenza vaccine. Any influenza vaccine (egg based or nonegg based) that is otherwise appropriate for the recipient's age and health status can be used (https://www.cdc.gov/vaccines/acip/recs/grade/influenza-egg-allergy.html; https://www.cdc.gov/vaccines/acip/recs/grade/influenza-egg-allergy-etr.html). It is no longer recommended that persons who have had an allergic reaction to egg involving symptoms other than urticaria should be vaccinated in an inpatient or outpatient medical setting supervised by a health care provider who is able to recognize and manage severe allergic reactions if an egg-based vaccine is used. Egg allergy alone necessitates no additional safety measures for influenza vaccination beyond those recommended for any recipient of any vaccine, regardless of severity of previous reaction to egg. All vaccines should be administered in settings in which personnel and equipment needed for rapid recognition and treatment of acute hypersensitivity reactions are available.

Most available influenza vaccines, with the exceptions of RIV4 (Flublok Quadrivalent, licensed for persons aged ≥18 years) and ccIIV4 (Flucelvax Quadrivalent, licensed for persons aged ≥6 months), are prepared by propagation of virus in embryonated eggs and might contain trace amounts of egg proteins, such as ovalbumin. Among those U.S.-licensed influenza vaccines for which ovalbumin content is reported, quantities are generally small (≤1 μg/0.5mL dose) (Table 1).

The Joint Task Force on Practice Parameters of the American Academy of Allergy, Asthma & Immunology (AAAAI) and the American College of Allergy, Asthma, & Immunology (ACAAI) have recommended that administration of influenza vaccine to egg allergic persons requires no additional precautions other than those recommended for administration of any vaccine to any individual (103). Since the 2016–17 influenza season, the American Academy of Pediatrics (AAP) has recommended that no additional precautionary measures are needed when administering influenza vaccine to egg-allergic persons (104). A review of 20 studies (16 of IIVs, one of virosomal influenza vaccine, and three of LAIV) that examined reactions after administration of seasonal influenza vaccines to egg-allergic persons via either full single-dose or split-dose administration protocols (of which 13 reported inclusion of persons with a history of severe reaction or anaphylaxis to egg) included no reports of anaphylaxis (certainty level: very low) (105–122). Less severe reactions not described as anaphylaxis but involving cardiovascular symptoms, respiratory symptoms, angioedema, or generalized urticaria, or which involved treatment with medications or outpatient or emergency department attention occurred with low frequency (<1%). A similar profile was noted among 13 studies of monovalent H1N1pdm09 influenza vaccine, with no reported instances of anaphylaxis; frequency of reactions involving cardiovascular symptoms, respiratory symptoms, angioedema, or generalized urticaria events of <1%, and of events involving treatment with medications or outpatient or emergency department attention of approximately 1.5% (certainty level: very low) (114,115,123–132). One instance of anaphylaxis meeting a surveillance case definition (i.e., Brighton Level 1 criteria) in a person with possible egg allergy was noted in a summary of VAERS reports after administration of monovalent H1N1pdm09 influenza vaccine during the 2009–10 influenza season; no denominator of doses administered was available but it was noted that approximately 127 million doses of monovalent IIV were distributed in the United States that season (133). Of note, severe allergic reactions after administration of the egg-free vaccine RIV to egg-allergic persons have been noted in VAERS reports (134–136). These reports highlight both the possibility that observed reactions after egg-based influenza vaccines might be caused by substances other than egg proteins and the importance of being prepared to recognize and manage serious hypersensitivity reactions when administering any vaccine to any recipient (regardless of allergy history).

Severe and life-threatening reactions to vaccines can rarely occur with any vaccine and in any vaccine recipient, regardless of allergy history. Providers are reminded that all vaccines should be administered in settings in which personnel and equipment needed for rapid recognition and treatment of acute hypersensitivity reactions are available. All vaccination providers should be familiar with their office emergency plan and be certified in cardiopulmonary resuscitation (47). No postvaccination observation period is recommended specifically for egg-allergic persons. However, ACIP recommends that vaccination providers consider observing patients (seated or supine) for 15 minutes after administration of any vaccine to decrease the risk for injury should syncope occur (47).

Although egg allergy is neither a contraindication nor precaution to the use of any influenza vaccine, there are contraindications and precautions related to allergies to vaccine components other than egg and to previous allergic reactions to influenza vaccines (see Persons with Previous Allergic Reactions to Influenza Vaccines and Dosage, Administration, Contraindications, and Precautions) (Tables 2 and 3).

Persons with Previous Allergic Reactions to Influenza Vaccines

As is the case for all vaccines, influenza vaccines contain various components that might cause allergic and anaphylactic reactions. Most influenza vaccine package inserts list among contraindications to their use a history of previous severe allergic reaction (e.g., anaphylaxis) to any component of the vaccine or to a previous dose of any influenza vaccine (48,49,51–53,55,56). For ccIIV4 and RIV4, a history of a severe allergic reaction to any vaccine component is listed as a contraindication; no labeled contraindication is specified for a history of allergic reaction to any other influenza vaccine (50,54). However, severe allergic reactions, although rare, can occur after influenza vaccination, even among persons with no previous reactions or known allergies. Vaccine components and excipients can be found in package inserts. However, identifying the causative agent without further evaluation (i.e., through evaluation and testing for specific allergies) can be difficult. Severe allergic reactions after vaccination with an RIV have been reported to VAERS, certain of which have occurred among persons reporting previous allergic reactions to egg or to influenza vaccines and that might represent a predisposition to development of allergic manifestations in affected persons (134–136). Because these rare but severe allergic reactions can occur, ACIP recommends the following for persons with a history of severe allergic reaction to a previous dose of an influenza vaccine (Table 3):

• For egg-based IIV4s and LAIV4:
  • A history of severe allergic reaction (e.g., anaphylaxis) to any influenza vaccine (i.e., any egg-based IIV, ccIIV, RIV, or LAIV of any valency) is a contraindication to future receipt of all egg-based IIV4s and LAIV4. Each individual egg-based IIV4 and LAIV4 is also contraindicated for persons who have had a severe allergic reaction (e.g., anaphylaxis) to any component of that vaccine (excluding egg; see Persons with a History of Egg Allergy).
• For ccIIV4:
  • A history of a severe allergic reaction (e.g., anaphylaxis) to any egg-based IIV, RIV, or LAIV of any valency is a precaution for the use of ccIIV4. If ccIIV4 is administered in such instances, vaccination should occur in an inpatient or outpatient medical setting and should be supervised by a health care provider who is able to recognize and manage severe allergic reactions. Providers also can consider consultation with an allergist to help determine the vaccine component responsible for the allergic reaction.
  • A history of a severe allergic reaction (e.g., anaphylaxis) to any ccIIV of any valency or to any component of ccIIV4 is a contraindication to future receipt of ccIIV4.
• For RIV4:
  • A history of a severe allergic reaction (e.g., anaphylaxis) to any egg-based IIV, ccIIV, or LAIV of any valency is a precaution for the use of RIV4. If RIV4 is administered in such instances, vaccination should occur in an inpatient or outpatient medical setting and should be supervised by a health care provider who is able to recognize and manage severe allergic reactions. Providers can also consider consultation with an allergist to help determine the vaccine component responsible for the allergic reaction.
  • A history of a severe allergic reaction (e.g., anaphylaxis) to any RIV of any valency or to any component of RIV4 is a contraindication to future receipt of RIV4.

Vaccination Issues for Travelers

In temperate climate regions of the Northern and Southern Hemispheres, influenza activity is seasonal, occurring during approximately October–May in the Northern Hemisphere and April–September in the Southern Hemisphere. In the tropics, influenza might occur throughout the year (137). The timing of influenza activity and predominant types and subtypes of influenza viruses in circulation vary by geographic region (138). Travelers can be exposed to influenza when traveling to an area where influenza is circulating or when traveling as part of large tourist groups (e.g., on cruise ships) that include persons from areas of the world where influenza viruses are circulating (139–142).

Travelers who want to reduce their risk for influenza should consider influenza vaccination, preferably at least 2 weeks before departure. In particular, persons who live in the United States and are at higher risk for influenza complications and who were not vaccinated with influenza vaccine during the previous Northern Hemisphere fall or winter should consider receiving influenza vaccination before departure if they plan to travel to the tropics, to the Southern Hemisphere during the Southern Hemisphere influenza season (April–September), or with organized tourist groups or on cruise ships to any location. Persons at higher risk who received the previous season's influenza vaccine before travel should consult with their health care provider to discuss the risk for influenza and other travel-related diseases before embarking on travel during the summer. All persons (regardless of risk status) who are vaccinated in preparation for travel before the upcoming influenza season's vaccine is available, or who received the immediately preceding Southern Hemisphere influenza vaccine, should receive the current U.S. seasonal influenza vaccine the following fall or winter.

Influenza vaccine formulated for the Southern Hemisphere might differ in viral composition from the Northern Hemisphere vaccine. For persons traveling to the Southern Hemisphere during the Southern Hemisphere influenza season, receipt of a current U.S.-licensed Southern Hemisphere influenza vaccine formulation before departure might be reasonable but might not be feasible because of limited access to or unavailability of Southern Hemisphere formulations in the United States. Most Southern Hemisphere influenza vaccine formulations are not licensed in the United States, and they are typically not commercially available. More information on influenza vaccines and travel is available at https://wwwnc.cdc.gov/travel/diseases/influenza-seasonal-zoonotic-and-pandemic. Additional information on global influenza surveillance by region is available at https://www.who.int/tools/flunet.

Use of Influenza Antiviral Medications

Administration of any IIV4 or RIV4 to persons receiving influenza antiviral medications for treatment or chemoprophylaxis of influenza is acceptable. Data concerning vaccination with LAIV4 in the setting of influenza antiviral use are not available. However, influenza antiviral medications might interfere with the action of LAIV4 because this vaccine contains live influenza viruses.

The package insert for LAIV4 notes that influenza antiviral agents might reduce the effectiveness of the vaccine if administered within the interval from 48 hours before to 14 days after vaccination (53). However, the newer influenza antivirals peramivir and baloxavir have longer half-lives than oseltamivir and zanamivir, approximately 20 hours for peramivir (143) and 79 hours for baloxavir (144), and could interfere with the replication of LAIV4, if administered >48 hours before vaccination. Potential interactions between influenza antivirals and LAIV4 have not been studied, and the ideal intervals between administration of these medications and LAIV4 are not known. Assuming a period of at least 5 half-lives for substantial decrease in drug levels (145), a reasonable assumption is that that peramivir might interfere with the mechanism of LAIV4 if administered from 5 days before through 2 weeks after vaccination and baloxavir might interfere if administered from 17 days before through 2 weeks after vaccination. The interval between influenza antiviral receipt and LAIV4 during which interference might occur could be further prolonged in the presence of medical conditions that delay medication clearance (e.g., renal insufficiency). Persons who receive these medications during these periods before or after receipt of LAIV4 should be revaccinated with another appropriate influenza vaccine (e.g., IIV4 or RIV4).

Administration of Influenza Vaccines with Other Vaccines

IIV4s and RIV4 can be administered simultaneously or sequentially with other inactivated vaccines or live vaccines. Injectable vaccines that are given concomitantly should be administered at separate anatomic sites. COVID-19 vaccines that are administered at the same time as influenza vaccines that might be more likely to be associated with local injection site reactions (e.g., HD-IIV4 and aIIV4) should be given in different limbs, if possible. LAIV4 can be administered simultaneously with other live or inactivated vaccines. However, if two live vaccines are not given simultaneously, at least 4 weeks should pass after administration of one live vaccine (such as LAIV4) before another live vaccine is administered (47).

In recent years, multiple vaccines containing nonaluminum adjuvants have been licensed for use in the United States for the prevention of various infectious diseases. Examples include AS01_B (in Shingrix, recombinant zoster subunit vaccine) (146), AS01_E (in Arexy, respiratory syncytial virus vaccine) (147) MF59 (in Fluad Quadrivalent [aIIV4]) (56), and cytosine phosphoguanine oligodeoxynucleotide (in Heplisav-B, a recombinant hepatitis B surface antigen vaccine) (148). Data are limited regarding coadministration of these vaccines with other adjuvanted or nonadjuvanted vaccines, including COVID-19 vaccines. Coadministration of Shingrix with nonadjuvanted IIV4 has been studied, and no evidence of decreased immunogenicity or safety concerns was noted (149). Data on the immunogenicity and safety of simultaneous or sequential administration of two nonaluminum adjuvant–containing vaccines are limited, and the ideal interval between such vaccines when given sequentially is not known. In the study of Shingrix and IIV4 (149), most reactogenicity symptoms resolved within 4 days. Because of the limited data on the safety of simultaneous administration of two or more vaccines containing nonaluminum adjuvants and the availability of nonadjuvanted influenza vaccine options, selection of a nonadjuvanted influenza vaccine may be considered in situations in which influenza vaccine and another vaccine containing a nonaluminum adjuvant are to be administered concomitantly. However, influenza vaccination should not be delayed if a specific vaccine is not available. As recommended for all vaccines, vaccines with nonaluminum adjuvants should be administered at separate anatomic sites from other vaccines that are given concomitantly (47).

For more recently introduced and new vaccines (e.g., respiratory syncytial virus [RSV] vaccine) data informing simultaneous administration with influenza vaccines might be limited or evolving. Providers should consult current CDC/ACIP recommendations and guidance for up-to-date information.

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