National Center for Immunization & Respiratory Diseases

WG Considerations and Proposed Influenza Vaccine 

Recommendations, 2021-22

Lisa Grohskopf, MD, MPH

Influenza Division, NCIRD, CDC

Advisory Committee on Immunization Practices

June 24, 2021
Acknowledgements

Influenza Division

Elif Alyanak

Noreen Alabi

Lenee Blanton

Lynnette Brammer

Alicia Budd

Jessie Chung

Vivien Dugan

Jill Ferdinands

Brendan Flannery

Alicia Fry

Krista Kniss

Manish Patel

Melissa Rolfes

Tim Uyeki

Immunization Safety Office

Karen Broder

Frank Destefano

Anamika Dua

Penina Haber

Tom Shimabukuro

Immunization Services Division

Sam Graitcer

Andrew Kroger

Amy Parker Fiebelkorn

Jeanne Santoli

Clinical Immunization Safety Assessment 

(CISA) Project
Overview
2021–22 ACIP Influenza Statement

▪ Core recommendation (unchanged):

– Annual influenza vaccination is recommended for all persons aged 6 months 

and older who do not have contraindications.

▪ Updates:

– Influenza vaccines expected to be available for the 2021-22 season

– U.S. influenza vaccine viral composition for the 2021-22 season

– Change in age indication for Flucelvax Quadrivalent from ≥4 years to ≥2 years

– Several changes to Timing of Vaccination language

– Co-administration of influenza and COVID-19 vaccines

– Contraindications and precautions concerning persons with previous severe 

allergic reaction to influenza vaccines or their components
Available Influenza Vaccines, 2021-22
Influenza Vaccines Expected to be Available by Age Indication, United States, 

2021–22 Influenza Season

Vaccine type 0 through 6

months

6 through 23 

months

2 through 17 

years

18 through 49 

years

50 through 64 

years

≥65 

years

IIV4s Standard-dose, 

unadjuvanted

inactivated

(IIV4)

Afluria Quadrivalent

Fluarix Quadrivalent

FluLaval Quadrivalent

Fluzone Quadrivalent

Cell culture-based 

inactivated (IIV4)

Flucelvax Quadrivalent

Adjuvanted

inactivated (aIIV4)

Fluad Quadrivalent

High-dose 

inactivated (HD-IIV4)

Fluzone High-Dose 

Quadrivalent

RIV4 Recombinant

(RIV4)

Flublok Quadrivalent

LAIV4 Live attenuated

(LAIV4)

FluMist Quadrivalent

All vaccines expected for 2021-22 are quadrivalent (i.e., contain hemagglutinin derived from four viruses:

one influenza A(H1N1), one influenza A(H3N2), one influenza B/Victoria and one influenza B/Yamagata.

IIV4=quadrivalent inactivated influenza vaccine RIV4=quadrivalent recombinant influenza vaccine LAIV4=quadrivalent live attenuated influenza vaccine

Not approved for age group Egg-based Not egg-based
2021-22 Influenza Vaccine Composition
2021–22 Influenza Vaccine Composition 

▪ Egg-based IIV4s and LAIV4:

– An A/Victoria/2570/2019 (H1N1)pdm09-like virus;

– An A/Cambodia/e0826360/2020 (H3N2)-like virus;

– A B/Washington/02/2019 (Victoria lineage)-like virus; and

– A B/Phuket/3073/2013 (Yamagata lineage)-like virus.

▪ Cell-culture-based IIV4 and RIV4:

– An A/Wisconsin/588/2019 (H1N1)pdm09-like virus;

– An A/Cambodia/e0826360/2020 (H3N2)-like virus;

– A B/Washington/02/2019 (Victoria lineage)-like virus; and

– A B/Phuket/3073/2013 (Yamagata lineage)-like virus.

UPDATED

UPDATED

UPDATED

UPDATED
Change in Age Indication for Flucelvax 

Quadrivalent (ccIIV4)
Change in Age Indication for Flucelvax Quadrivalent 

Cell culture-based inactivated influenza vaccine (ccIIV4).

▪ Previously licensed for ages ≥4 years; approved in March 2021 for ages ≥2 years.

▪ Change supported by randomized trial conducted among 4,514 children aged ≥2 

through <18 years over three influenza seasons: (Southern Hemisphere 2017 and 

Northern Hemisphere 2017-18 and 2018-19).

▪ Randomized 1:1 to receive ccIIV4 or meningococcal serogroup ACWY conjugate 

vaccine. 

▪ Overall vaccine efficacy 54.6% (95%CI 45.7, 62.1) against RT-PCR or culture) influenzaassociated CDC-defined influenza-like illness.

▪ Vaccine efficacy 62.7% (95%CI 38.1, 80.8) for matched strains.

▪ Data presented to ACIP in October, 2020.

▪ New age indication reflected in text and in Table 1.
Co-Administration of Influenza Vaccines 

with COVID-19 Vaccines
Co-administration of Influenza Vaccines with COVID-19 Vaccines

▪ Section on co-administration of influenza vaccines with other vaccines 

updated to reflect availability of COVID-19 vaccines.

▪ Considerations discussed:

– Potential for increased reactogenicity, particularly with influenza vaccines that 

might be more likely to cause local or systemic reactions.

• Greater frequency of reactogenicity with adjuvanted and high-dose inactivated 

vaccines compared with standard-dose, unadjuvanted inactivated vaccines in some 

studies.

• These vaccines approved only for ages 65+ in the U.S.

– Importance of not missing opportunities for vaccination.

▪ Language consistent with most current COVID-19 vaccination guidance.

▪ Refers providers to most recent guidance for any updated information.
Co-administration of Influenza Vaccines with COVID-19 Vaccines

▪ From the “Interim Clinical Considerations for Use of COVID-19 Vaccines 

Currently Authorized in the United States”

– “COVID-19 vaccines were previously recommended to be administered alone, 

with a minimum interval of 14 days before or after administration of any other 

vaccines. This was out of an abundance of caution and not due to any known 

safety or immunogenicity concerns. However, substantial data have now been 

collected regarding the safety of COVID-19 vaccine currently authorized by FDA 

for use under EUA...COVID-19 vaccines and other vaccines may now be 

administered without regard to timing.” 

– “Administer the COVID-19 vaccines and vaccines that may be more likely to cause 

a local reaction (e.g., tetanus-toxoid-containing and adjuvanted vaccines) in 

different limbs, if possible.”

https://www.cdc.gov/vaccines/covid-19/info-by-product/clinical-considerations.html
Co-administration of Influenza Vaccines with COVID-19 Vaccines

▪ Proposed Language for 2021-22 Influenza Statement

– Current guidance concerning administration of COVID-19 vaccines with other 

vaccines (https://www.cdc.gov/vaccines/covid-19/info-by-product/clinicalconsiderations.html) indicates that these vaccine may be given with other 

vaccines, including influenza vaccines. No data are currently available concerning 

coadministration of currently authorized COVID-19 vaccines and influenza 

vaccines. Providers should be aware of the potential for increased reactogenicity 

with coadministration, and should consult CDC guidance at the referenced link for 

updated guidance as more information becomes available. If coadministered, 

COVID-19 vaccines and vaccines that might be more likely to cause a local 

reaction (e.g., aIIV4 or HD-IIV4) should be administered in different limbs, if 

possible.
Timing of Vaccination
Timing of Influenza Seasons 

▪ Timing of the onset and peak 

of influenza activity varies 

from season to season

▪ Timing of activity onset can 

also vary geographically

▪ In the United States, 

localized areas of increased 

activity occur as early as 

October

▪ Over the 36 seasons 

between 1982-83 and 2017-

18, peak activity occurred 

in:1

• December 7 (19%) seasons

• January 6 (17%) seasons

• February 15 (42%) seasons

• March 6 (19%) seasons

1--https://www.cdc.gov/flu/about/season/flu-season.htm
Waning of Protection Following Vaccination 

▪ Current 2020-21 statement contains a discussion of evidence for waning 

protection following vaccination

– Declines in influenza vaccine effectiveness over the course of the 

season have been observed in many observational studies.

– Appears to be more pronounced among older adults

– Less evidence for waning among children
Timing of Influenza Vaccination--Background 

▪ Vaccination has been recommended to be offered by the end of October, 

and to continue as long as influenza viruses are circulating locally

▪ Language has included recommendation that July and August are probably 

too early for vaccination in most influenza seasons, particularly for older 

adults.

– Exception made for those children ages 6 months through 8 years who 

require two doses for the season, for whom receipt of the first dose is 

recommended as soon as possible after vaccine is available (since 

doses must be ≥4 weeks apart). 
Timing of Influenza Vaccination—Work Group Considerations 

▪ WG discussed recent literature concerning waning of immunity to influenza 

vaccines.

▪ Other considerations discussed included

– Protection of infants during first months of life (since there is are licensed 

influenza vaccines for children under age 6 months). 

– Avoiding missed opportunities for vaccination

▪ Language contains several changes concerning timing of vaccination for 

children, persons in the third trimester of pregnancy, and adults.
Timing of Influenza Vaccination—Proposed Language: Children 

▪ Similar to previous:

“Children aged 6 months through 8 years who require 2 doses should receive 

their first dose as soon as possible after the vaccine becomes available to 

allow the second dose (which must be administered ≥4 weeks later) to be 

received ideally by the end of October.”

▪ New:

“Children of any age who require only one dose for the season should also 

ideally be vaccinated by the end of October; vaccination of these children 

may occur as soon as vaccine is available, as there is less evidence to suggest 

that early vaccination is associated with waning immunity among children as 

compared with adults.”
Timing of Influenza Vaccination—Proposed Language: Pregnant 

Persons in Third Trimester 

▪ New:

“Vaccination soon after vaccine becomes available may also be considered 

for pregnant persons during the third trimester, as vaccination of pregnant 

persons has been shown to reduce risk of influenza illness of their infants 

during the first months of life1-4(a period during which they be too young to 

receive influenza vaccine)”

1-Madhi et al N Engl J Med. 2014 Sep 4;371(10):918-31.

2-Tapia et al Lancet Infect Dis. 2016 Sep;16(9):1026-35.

3-Steinhoff et al Lancet Infect Dis. 2017 Sep;17(9):981-9.

4-Eick et al Arch Pediatr Adolesc Med. 2011 Feb;165(2):104-11.
Timing of Influenza Vaccination—Proposed Language: NonPregnant Adults 

▪ New

“For non-pregnant adults, influenza vaccination during July and August 

should be avoided unless there is concern that later vaccination might not be 

possible.”
Influenza Vaccine Contraindications and 

Precautions—Allergic Reactions to 

Influenza Vaccines or their Components
Allergic Reactions to Influenza Vaccines--Background

▪ Vaccines (including influenza vaccines) include multiple components that can 

potentially trigger severe allergic reactions (e.g., anaphylaxis)

▪ Serious allergic reactions to influenza vaccine are rare

– In one Vaccine Safety Datalink (VSD) study1the estimated rates of postvaccination anaphylaxis among cases that involved administration of a single 

vaccine.1

• 1.31 cases per million doses for all vaccines

• 1.35 cases per million doses for IIV3

1--McNeil J Allerg Clin Immunol 2016;137:868-878
Allergic Reactions to Influenza Vaccines--Background

▪ It can be difficult to know the component responsible for a severe allergic 

reaction.

▪ ACIP General Best Practices: 

– “Referral of the individual to an allergist for evaluation is usually 

indicated to possibly determine the component responsible, before 

making decisions regarding administration of the additional doses of the 

same vaccine or other vaccines that have the same components.” 

1--https://www.cdc.gov/vaccines/hcp/acip-recs/general-recs/downloads/general-recs.pdf
Allergic Reactions to Influenza Vaccines--Background

Current (2020-21) language (from egg allergy section)

“A previous severe allergic reaction to influenza vaccine, regardless of the 

component suspected of being responsible for the reaction, is a 

contraindication to future receipt of the vaccine.”

Package insert contraindications language for egg-based IIVs

▪ History of severe allergic reaction (e.g. anaphylaxis) to any component of the 

vaccine (including egg protein), or after a previous dose of any influenza 

vaccine.
Allergic Reactions to Influenza Vaccines--Background

▪ Package insert contraindications language for RIV4 (Flublok Quadrivalent) 

and ccIIV4 (Flucelvax Quadrivalent):

– History of severe allergic reactions (e.g., anaphylaxis) to any component 

of the vaccine. 

▪ In the current statement, Table 2 (Contraindications and Precautions):

– All IIVs (including ccIIV4):

• ”History of severe allergic reaction to any component of the 

vaccine, or to a previous dose of any influenza vaccine”

– RIV4: 

• Reflects the package insert language: “History of severe allergic 

reaction to any component of the vaccine”
Allergic Reactions to Influenza Vaccines--Considerations

▪ Consistency and simplicity of recommendations

▪ Harmonization with influenza vaccine package inserts

▪ Relative compositions of currently available influenza vaccines

▪ Extending vaccination to those who have had a severe allergic reaction to 

influenza vaccine, if an alternative vaccine can be received safely

▪ Potential need for allergy/immunology consultation
Allergic Reactions to Influenza Vaccines--Considerations

▪ Woo et al analyses of Vaccine Adverse Event Reporting System (VAERS) data

– Evaluated reports of cases of severe allergic reactions following 

recombinant influenza vaccine (RIV) 1, 2

▪ Limitations of VAERS:

– Passive surveillance

– Potential for reporting bias

– Inconsistent data quality and completeness

– Generally cannot assess causality

Woo et al, Clin Infect Dis 2015;60(5):777-780

Woo et al, Vaccine 2017;35:5618-5621
Allergic Reactions to Influenza Vaccines--Considerations

▪ Woo et al analyses of Vaccine Adverse Event Reporting System (VAERS) data

– Evaluated reports of cases of severe allergic reactions following 

recombinant influenza vaccine (RIV) 

• Egg-free, without antibiotics, gelatin, or preservatives

– Noted cases of allergic reactions, some meeting Brighton criteria for 

anaphylaxis, some among persons who had reported a history of allergic 

reaction to egg or to a previous dose of influenza vaccine.

▪ Authors note that the occurrence of such reactions might reflect an 

underlying predisposition to atopy which might lead to reactions following 

any vaccine, rather than to indicate a relationship to the components of a 

specific vaccine.
Proposed Contraindication and Precautions—Table 2 

Vaccine 

Type

Contraindications Precautions

Egg-based 

IIV4s

History of severe allergic reaction to any component of the vaccine, or to 

a previous dose of any influenza vaccine (i.e., any IIV, RIV, or LAIV)†§

Moderate or severe acute illness with or 

without fever

History of Guillain-Barré syndrome within 6 

weeks of receipt of influenza vaccine

cIIV4 History of severe allergic reaction to ccIIV4, cIIV3 or to any component of 

ccIIV4§

Moderate or severe acute illness with or 

without fever

History of Guillain-Barré syndrome within 6 

weeks of receipt of influenza vaccine

History of severe allergic reaction to a 

previous dose of any other influenza vaccine 

(i.e., egg-based IIV, RIV, or LAIV)¶

RIV4 History of severe allergic reaction to RIV4, RIV3 or to any component of 

RIV4§

Moderate or severe acute illness with or 

without fever

History of Guillain-Barré syndrome within 6 

weeks of receipt of influenza vaccine

History of severe allergic reaction to a 

previous dose of any other influenza vaccine 

(i.e., any IIV or LAIV)¶
Proposed Contraindications and Precautions

Additional footnotes concerning precautions:

▪ If ccIIV4 or RIV4 is administered to an individual with a history of severe 

allergic reaction (e.g., anaphylaxis) to any other influenza vaccine, 

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. 
Thank you!