Influenza vaccine: Difference between revisions

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| tradename = Afluria, Fluarix, Fluzone, others

| legal_AU_comment = <ref name="AusPAR: Influenza Haemagglutinin Recombinant" /><ref name="AusPAR: Inactivated quadrivalent influenza vaccine (split virion) influenza virus haemagglutinin" /><ref>{{cite web | title=Prescription medicines: registration of new chemical entities in Australia, 2017 | website=Therapeutic Goods Administration (TGA) | date=June 21, 2022 | url=https://www.tga.gov.au/resources/publication/publications/prescription-medicines-registration-new-chemical-entities-australia-2017 | access-date=April 9, 2023 | archive-date=April 10, 2023 | archive-url=https://web.archive.org/web/20230410060848/https://www.tga.gov.au/resources/publication/publications/prescription-medicines-registration-new-chemical-entities-australia-2017 | url-status=live }}</ref><ref>{{cite web | title=Prescription medicines: registration of new chemical entities in Australia, 2016 | website=Therapeutic Goods Administration (TGA) | date=June 21, 2022 | url=https://www.tga.gov.au/prescription-medicines-registration-new-chemical-entities-australia-2016 | access-date=April 10, 2023 | archive-date=April 10, 2023 | archive-url=https://web.archive.org/web/20230410065503/https://www.tga.gov.au/prescription-medicines-registration-new-chemical-entities-australia-2016 | url-status=live }}</ref><ref>https://www.tga.gov.au/resources/auspar/auspar-flucelvax-quad-0 {{Bare URL inline|date=August 2024}}</ref>

| legal_EU_comment = <ref>{{cite web | title=Supemtek EPAR | website=European Medicines Agency | date=November 25, 2020 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/supemtek | access-date=June 27, 2024}}</ref><ref>{{cite web | title=Fluad Tetra | website=European Medicines Agency (EMA) | date=May 20, 2020 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/fluad-tetra | access-date=August 10, 2024}}</ref>

'''Influenza vaccines''', colloquially known as '''flu shots'''<ref>{{cite web |title=Key Facts About Seasonal Flu Vaccine |url=https://www.cdc.gov/flu/vaccines/keyfacts.html |website=Influenza (Flu) |language=en-us |date=30 September 2024}}</ref> or the '''flu jab''',<ref>{{cite web |title=The flu jab in pregnancy |url=https://www.nhs.uk/pregnancy/keeping-well/flu-jab/ |website=nhs.uk |language=en |date=3 December 2020}}</ref> are [[vaccine]]s that protect against infection by [[influenza viruses]].<ref name=WHO2012>{{cite journal |author=World Health Organization | author-link = World Health Organization | title = Vaccines against influenza WHO position paper | journal = Weekly Epidemiological Record | volume = 87 | issue = 47 | pages = 461–76 | date = November 2012 | pmid = 23210147 | hdl=10665/241993 | hdl-access=free }}</ref><ref name=WHO2022>{{cite journal |author=World Health Organization | author-link = World Health Organization | title = Vaccines against influenza: WHO position paper – May 2022 | journal = Weekly Epidemiological Record | volume = 97 | issue = 19 | pages = 185–208 | date = May 2022 | hdl=10665/354265 | hdl-access=free }}</ref> New versions of the vaccines are developed twice a year, as the influenza virus rapidly changes.<ref name=WHO2012/> While their effectiveness varies from year to year, most provide modest to high protection against [[influenza]].<ref name=WHO2012/><ref name=Man2012>{{cite journal | vauthors = Manzoli L, Ioannidis JP, Flacco ME, De Vito C, Villari P | title = Effectiveness and harms of seasonal and pandemic influenza vaccines in children, adults and elderly: a critical review and re-analysis of 15 meta-analyses | journal = Human Vaccines & Immunotherapeutics | volume = 8 | issue = 7 | pages = 851–62 | date = July 2012 | pmid = 22777099 | pmc = 3495721 | doi = 10.4161/hv.19917 | author-link2 = John P.A. Ioannidis }}</ref> Vaccination against influenza began in the 1930s, with large-scale availability in the United States beginning in 1945.<ref>{{cite book |url=https://books.google.com/books?id=uOE-3atWZssC&pg=PA49 |title=Vaccines for pandemic influenza |vauthors=Compans RW |date=2009 |publisher=Springer |isbn=978-3-540-92165-3 |location=Dordrecht |page=49 |access-date=September 9, 2017 |archive-url=https://web.archive.org/web/20200803101300/https://books.google.com/books?id=uOE-3atWZssC&pg=PA49 |archive-date=August 3, 2020 |url-status=live}}</ref><ref>{{cite book |url=https://books.google.com/books?id=vJKeBQAAQBAJ&pg=PA61 |title=Vaccine Analysis: Strategies, Principles, and Control |date=2014 |publisher=Springer |isbn=978-3-662-45024-6 |page=61 |access-date=September 9, 2017 |archive-url=https://web.archive.org/web/20200803141329/https://books.google.com/books?id=vJKeBQAAQBAJ&pg=PA61 |archive-date=August 3, 2020 |url-status=live}}</ref>

Both the [[World Health Organization]] and the US [[Centers for Disease Control and Prevention]] (CDC) recommend yearly vaccination for nearly all people over the age of six months, especially those at high risk,<ref name="WHO2012" /><ref name="WhoShouldVax">{{cite web |date=October 11, 2019 |title=Who Should and Who Should NOT get a Flu Vaccine |url=https://www.cdc.gov/flu/prevent/whoshouldvax.htm |url-status=live |archive-url=https://web.archive.org/web/20191202202838/https://www.cdc.gov/flu/prevent/whoshouldvax.htm |archive-date=December 2, 2019 |access-date=December 2, 2019 |website=U.S. [[Centers for Disease Control and Prevention]] (CDC)}} {{PD-notice}}</ref><ref>{{cite book |title=The immunological basis for immunization series: module 23: influenza vaccines |date=October 2017 |publisher=[[World Health Organization]] (WHO) |isbn=978-92-4-151305-0 |hdl=10665/259211 |hdl-access=free}}</ref><ref name="pmid34448800" /> and the influenza vaccine is now on the [[WHO Model List of Essential Medicines|WHOWorld Health Organization's List of Essential Medicines]].<ref name="WHO21stWHO23rd">{{cite book |title vauthors = ((World Health Organization)) model| listtitle = The selection and use of essential medicines 2023: 21stweb listannex 2019A: |publisher=[[World Health Organization]] |year=2019model |location=Genevalist |hdl=10665/325771of |id=WHO/MVP/EMP/IAU/2019.06.essential Licensemedicines: CC23rd BY-NC-SAlist 3.0(2023) IGO| year |hdl-access=free 2023 |last1=Organization |first1hdl =World Health }}<10665/ref><ref371090 name="WHO22nd">{{cite| bookauthor-link |title= World Health Organization model| listpublisher of= essential medicines: 22nd list (2021) |publisher=[[World Health Organization]] |year=2021 |location = Geneva |hdl=10665/345533 |id = WHO/MHP/HPS/EML/20212023.02 | hdl-access=free |last1=Organization |first1=World Health }}</ref> The [[European Centre for Disease Prevention and Control]] (ECDC) also recommends yearly vaccination of high-risk groups,<ref>{{cite web | title=Implementation of the Council Recommendation on seasonal influenza vaccination (2009/1019/EU) | website=[[European Centre for Disease Prevention and Control]] | date=January 2014 | url=https://www.ecdc.europa.eu/sites/default/files/media/en/publications/Publications/Implementation-seasonal-influenza-vaccination-Council-Recommendation-Jan-2014.pdf |access-date=April 10, 2020 | archive-date=April 10, 2020 | archive-url=https://web.archive.org/web/20200410223651/https://www.ecdc.europa.eu/sites/default/files/media/en/publications/Publications/Implementation-seasonal-influenza-vaccination-Council-Recommendation-Jan-2014.pdf | url-status=live }}

The vaccines are generally safe, including for people who have severe [[egg allergy|egg allergies]].<ref name="CDCegg">{{cite web |date=November 25, 2019 |title=Flu Vaccine and People with Egg Allergies |url=https://www.cdc.gov/flu/prevent/egg-allergies.htm |url-status=live |archive-url=https://web.archive.org/web/20191202200432/https://www.cdc.gov/flu/prevent/egg-allergies.htm |archive-date=December 2, 2019 |access-date=December 2, 2019 |publisher=U.S. [[Centers for Disease Control and Prevention]] (CDC)}} {{PD-notice}}</ref> A common [[side effect]] is soreness near the site of injection. [[Fever]] occurs in five to ten percent of children vaccinated, and temporary muscle pains or feelings of tiredness may occur. In certain years, the vaccine was linked to an increase in [[Guillain–Barré syndrome]] among older people at a rate of about one case per million doses.<ref name="WHO2012" /> Influenza vaccines are not recommended in those who have had a [[anaphylaxis|severe allergy]] to previous versions of the vaccine itself.<ref name="WHO2012" /><ref name="CDCegg" /> The vaccine comes in ''[[Inactivated vaccine|inactive]]'' and ''[[Attenuated vaccine|weakened]]'' viral forms. The live, weakened vaccine is generally not recommended in pregnant women, children less than two years old, adults older than 50, or people with a [[Immunocompromisation|weakened immune system]].<ref name=WHO2012/> Depending on the type it can be [[intramuscular|injected into a muscle (intramuscular)]], [[intranasal|sprayed into the nose]] (intranasal), or [[intradermal|injected into the middle layer of the skin]] (intradermal).<ref name=WHO2012/> The intradermal vaccine was not available during the 2018–2019 and 2019–2020 influenza seasons.<ref>{{cite web | title=Intradermal Influenza (Flu) Vaccination | website=U.S. [[Centers for Disease Control and Prevention]] (CDC) | date=October 31, 2018 | url=https://www.cdc.gov/flu/prevent/qa_intradermal-vaccine.htm | archive-url=https://web.archive.org/web/20191014052917/https://www.cdc.gov/flu/prevent/qa_intradermal-vaccine.htm | archive-date=October 14, 2019 | url-status=live | access-date=October 14, 2019}} {{PD-notice}}</ref><ref>{{cite web | title=Influenza vaccines – United States, 2019–20 influenza season | website=U.S. [[Centers for Disease Control and Prevention]] (CDC) | date=August 22, 2019 | url=https://www.cdc.gov/flu/professionals/vaccines.htm | archive-url=https://web.archive.org/web/20191014053637/https://www.cdc.gov/flu/professionals/vaccines.htm | archive-date=October 14, 2019 | url-status=live | access-date=October 14, 2019}} {{PD-notice}}</ref><ref name=AHFS2018>{{cite web | title = Influenza Virus Vaccine Inactivated | url = https://www.drugs.com/monograph/influenza-virus-vaccine-inactivated.html | publisher = The American Society of Health-System Pharmacists | date=November 19, 2018 | access-date = October 13, 2019 | url-status = live | archive-url = https://web.archive.org/web/20191014051931/https://www.drugs.com/monograph/influenza-virus-vaccine-inactivated.html | archive-date = October 14, 2019 }}</ref>

During the worldwide [[Spanish flu]] pandemic of 1918, "Pharmacists tried everything they knew, everything they had ever heard of, from the ancient art of [[bleeding]] patients, to [[oxygenotherapy|administering oxygen]], to developing new vaccines and serums (chiefly against what we now call ''[[Hemophilus influenzae]]''{{snd}}a name derived from the fact that it was originally considered the etiological agent{{snd}}and several types of pneumococci). Only one therapeutic measure, transfusing [[antiserum|blood from recovered patients]] to new victims, showed any hint of success."<ref>{{cite book |author=Institute of Medicine | veditors=Knobler SL, Mack A, Mahmoud A, Lemon SM |title=The Threat of Pandemic Influenza: Are We Ready? Workshop Summary |publisher=The National Academies Press|page=62 |year=2005 |pmid=20669448 |doi=10.17226/11150 |isbn=978-0-309-09504-4 }}</ref>

The B/Yamagata lineage of [[influenza B]], one of the four lineages targeted by quadrivalent vaccines, might have become extinct in 2020/2021 due to [[COVID-19 pandemic]] measures,<ref name="Koutsakos2021">{{cite journal | vauthors = Koutsakos M, Wheatley AK, Laurie K, Kent SJ, Rockman S | title = Influenza lineage extinction during the COVID-19 pandemic? | journal = Nature Reviews. Microbiology | volume = 19 | issue = 12 | pages = 741–742 | date = December 2021 | pmid = 34584246 | pmc = 8477979 | doi = 10.1038/s41579-021-00642-4 }}</ref> and there have been no naturally occurring cases confirmed since March 2020.<ref name="WHOflu2023"/><ref name="UMN2023"/> In 2023, the [[World Health Organization]] concluded that protection against the Yamagata lineage was no longer necessary in the seasonal flu vaccine, so future vaccines are recommended to be trivalent instead of quadrivalent.<ref name="WHOflu2023">{{cite web | title=Questions and Answers: Recommended composition of influenza virus vaccines for use in the southern hemisphere 2024 influenza season and development of candidate vaccine viruses for pandemic preparedness | author=[[World Health Organization]] | url=https://cdn.who.int/media/docs/default-source/influenza/who-influenza-recommendations/vcm-southern-hemisphere-recommendation-2024/202309_qanda_recommendation.pdf?sfvrsn=7a6906d1_5 | date=September 29, 2023 | access-date=October 26, 2023 | archive-date=October 10, 2023 | archive-url=https://web.archive.org/web/20231010045859/https://cdn.who.int/media/docs/default-source/influenza/who-influenza-recommendations/vcm-southern-hemisphere-recommendation-2024/202309_qanda_recommendation.pdf?sfvrsn=7a6906d1_5 | url-status=live }}</ref><ref name="UMN2023">{{cite web | title=WHO advisers recommend switch back to trivalent flu vaccines | authorvauthors = Schnirring L | website=CIDRAP | date=September 29, 2023 | url=https://www.cidrap.umn.edu/influenza-vaccines/who-advisers-recommend-switch-back-trivalent-flu-vaccines | access-date=October 26, 2023 | archive-date=December 18, 2023 | archive-url=https://web.archive.org/web/20231218231207/https://www.cidrap.umn.edu/influenza-vaccines/who-advisers-recommend-switch-back-trivalent-flu-vaccines | url-status=live }}</ref> For the 2024–2025 Northern Hemisphere influenza season, the FDA recommends removing B/Yamagata from all influenza vaccines.<ref name="FDA 2024–2025" />

|caption=US vaccine effectiveness (%) against [[symptomatic]] disease.<ref name="cdc-flu-effectiveness">{{cite web | title=Past Seasons Vaccine Effectiveness Estimates | website=U.S. [[Centers for Disease Control and Prevention]] (CDC) | date=January 29, 2020 | url=https://www.cdc.gov/flu/vaccines-work/past-seasons-estimates.html | archive-url=https://web.archive.org/web/20200212115345/https://www.cdc.gov/flu/vaccines-work/past-seasons-estimates.html | archive-date=February 12, 2020 | url-status=live | access-date=March 4, 2019}} {{PD-notice}}</ref><ref>{{Cite journal |publisher=Centers for Disease Control and Prevention |date=August 13, 2004 |title=Assessment of the effectiveness of the 2003-04 influenza vaccine among children and adults--Colorado, 2003 |url=https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5331a1.htm |journal=MMWR. Morbidity and Mortality Weekly Report |volume=53 |issue=31 |pages=707–710 |issn=1545-861X |pmid=15306754 |author1=Centers for Disease Control Prevention (CDC) |access-date=April 27, 2022 |archive-date=April 27, 2022 |archive-url=https://web.archive.org/web/20220427184713/https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5331a1.htm |url-status=live }} At table.</ref><ref>{{Cite journal |publisher=Centers for Disease Control and Prevention |date=January 16, 2004 |title=Preliminary assessment of the effectiveness of the 2003-04 inactivated influenza vaccine--Colorado, December 2003 |url=https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5301a3.htm |journal=MMWR. Morbidity and Mortality Weekly Report |volume=53 |issue=1 |pages=8–11 |issn=1545-861X |pmid=14724559 |author1=Centers for Disease Control Prevention (CDC) |access-date=April 25, 2022 |archive-date=May 29, 2022 |archive-url=https://web.archive.org/web/20220529044407/https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5301a3.htm |url-status=live }}</ref><ref>{{cite web |title=Past Weekly Surveillance Reports |url=https://www.cdc.gov/flu/weekly/pastreports.htm |website=Centers for Disease Control and Prevention |date=April 29, 2022 |access-date=April 25, 2022 |archive-date=April 22, 2022 |archive-url=https://web.archive.org/web/20220422191530/https://www.cdc.gov/flu/weekly/pastreports.htm |url-status=live }}</ref><ref>{{Cite journal |vauthors=Chung JR |date=March 11, 2022 |title=Interim Estimates of 2021–22 Seasonal Influenza Vaccine Effectiveness — United States, February 2022 |url=https://www.cdc.gov/mmwr/volumes/71/wr/mm7110a1.htm |journal=MMWR. Morbidity and Mortality Weekly Report |volume=71 |issue=10 |pages=365–370 |doi=10.15585/mmwr.mm7110a1 |pmid=35271561 |pmc=8911998 |issn=0149-2195 |access-date=May 25, 2022 |archive-date=May 16, 2022 |archive-url=https://web.archive.org/web/20220516045141/https://www.cdc.gov/mmwr/volumes/71/wr/mm7110a1.htm |url-status=live }}</ref> Notes: inestimable for the 2020–2021 flu season,<ref name="unable to estimate">{{cite web|url=https://www.healio.com/news/infectious-disease/20210603/cdc-unable-to-estimate-flu-vaccine-effectiveness-after-historically-mild-season|title=CDC unable to estimate flu vaccine effectiveness after historically mild season|author=Eamon N.vauthors = Dreisbach EN |publisher=Healio|date=June 3, 2021|access-date=April 18, 2022|archive-url=https://web.archive.org/web/20211008092935/https://www.healio.com/news/infectious-disease/20210603/cdc-unable-to-estimate-flu-vaccine-effectiveness-after-historically-mild-season|archive-date=October 8, 2021|url-status=live}}</ref> data missing for seasons 1999–2000 to 2002–2003.

From 2012 to 2015 in New Zealand, vaccine effectiveness against admission to an [[intensive care unit]] was 82%.<ref>{{Cite journal |vauthors=Thompson MG, Pierse N, Huang QS, Prasad N, Duque J, Newbern EC, Baker MG, Turner N, McArthur C |date=September 18, 2018 |title=Influenza vaccine effectiveness in preventing influenza-associated intensive care admissions and attenuating severe disease among adults in New Zealand 2012–2015 |url=https://www.sciencedirect.com/science/article/pii/S0264410X18309976 |journal=Vaccine |volume=36 |issue=39 |pages=5916–5925 |doi=10.1016/j.vaccine.2018.07.028 |pmid=30077480 |s2cid=51922011 |issn=0264-410X |access-date=April 23, 2022 |archive-date=May 27, 2022 |archive-url=https://web.archive.org/web/20220527070911/https://www.sciencedirect.com/science/article/pii/S0264410X18309976 |url-status=live }}</ref> Effectiveness against hospitalized influenza illness in the [[2019–2020 United States flu season]] was 41% overall and 54% in people aged 65 years or older.<ref>{{cite journal |vauthors=Tenforde MW, Talbot HK, Trabue CH, Gaglani M, McNeal TS, Monto AS, Martin ET, Zimmerman RK, Silveira FP, Middleton DB, Olson SM |title=Influenza Vaccine Effectiveness Against Hospitalization in the United States, 2019–2020 |journal=The Journal of Infectious Diseases |date=December 30, 2020 |volume=224 |issue=5 |pages=813–820 |doi=10.1093/infdis/jiaa800 |pmid=33378531 |pmc=8408767 |url=https://academic.oup.com/jid/article/224/5/813/6055595 |issn=0022-1899 |access-date=April 23, 2022 |archive-date=April 23, 2022 |archive-url=https://web.archive.org/web/20220423225806/https://academic.oup.com/jid/article/224/5/813/6055595 |url-status=live }}</ref> One review found 31% effectiveness against death among adults.<ref>{{Cite journal |vauthors=Ferdinands JM, Thompson MG, Blanton L, Spencer S, Grant L, Fry AM |date=June 23, 2021 |title=Does influenza vaccination attenuate the severity of breakthrough infections? A narrative review and recommendations for further research |url=https://www.sciencedirect.com/science/article/pii/S0264410X21005624 |journal=Vaccine |volume=39 |issue=28 |pages=3678–3695 |doi=10.1016/j.vaccine.2021.05.011 |pmid=34090700 |s2cid=235361401 |issn=0264-410X |access-date=April 23, 2022 |archive-date=April 23, 2022 |archive-url=https://web.archive.org/web/20220423225806/https://www.sciencedirect.com/science/article/pii/S0264410X21005624 |url-status=live }}</ref><ref name="CDC Effectiveness" />

Repeated annual influenza vaccination generally offers consistent year-on-year protection against influenza.<ref name="CDC Effectiveness" /> There is, however, suggestive evidence that repeated vaccinations may cause a reduction in vaccine effectiveness for certain influenza subtypes; this has no relevance to current recommendations for yearly vaccinations but might influence future vaccination policy.<ref name="pmid30626399">{{cite journal |vauthors=Ramsay LC, Buchan SA, Stirling RG, Cowling BJ, Feng S, Kwong JC, Warshawsky BF |title=The impact of repeated vaccination on influenza vaccine effectiveness: a systematic review and meta-analysis |journal=BMC Med |volume=17 |issue=1 |page=9 |date=January 2019 |pmid=30626399 |pmc=6327561 |doi=10.1186/s12916-018-1239-8 |doi-access = free }}</ref><ref>{{cite journal |vauthors=Belongia EA, Skowronski DM, McLean HQ, Chambers C, Sundaram ME, De Serres G |title=Repeated annual influenza vaccination and vaccine effectiveness: review of evidence |journal=Expert Rev Vaccines |volume=16 |issue=7 |pages=723–36 |date=July 2017 |pmid=28562111 |doi=10.1080/14760584.2017.1334554 | doi-access = free | title-link = doi }}</ref> {{As of|2019}}, the CDC recommends a yearly vaccine as most studies demonstrate overall effectiveness of annual influenza vaccination.<ref name="CDC Effectiveness">{{cite web | title=Vaccine Effectiveness: How Well Do the Flu Vaccines Work? | website=U.S. [[Centers for Disease Control and Prevention]] (CDC) | date=October 12, 2018 | url=https://www.cdc.gov/flu/vaccines-work/vaccineeffect.htm | archive-url=https://web.archive.org/web/20191025023838/https://www.cdc.gov/flu/vaccines-work/vaccineeffect.htm | archive-date=October 25, 2019 | url-status=live | access-date=October 24, 2019}} {{PD-notice}}</ref>

In April 2002, the Advisory Committee on Immunization Practices (ACIP) encouraged that children 6 to 23 months of age be vaccinated annually against influenza.<ref name="ReferenceC">{{Cite web|url = https://www.cdc.gov/flu/pandemic-resources/pandemic-timeline-1930-and-beyond.htm|title = Influenza Historic Timeline &#124; Pandemic Influenza (Flu) &#124; CDC|date = March 11, 2020|access-date = January 27, 2022|archive-date = January 30, 2022|archive-url = https://web.archive.org/web/20220130090654/https://www.cdc.gov/flu/pandemic-resources/pandemic-timeline-1930-and-beyond.htm|url-status = live}}</ref> In 2010, ACIP recommended annual influenza vaccination for those 6 months of age and older.<ref name="ReferenceC"/> Currently theThe CDC recommends that everyone except [[infant]]s under the age of six months should receive the seasonal influenza vaccine.<ref name="WhoShouldVax"/> [[Vaccination policy|Vaccination campaigns]] usually focus special attention on people who are at high risk of [[Influenza#Prognosis|serious complications]] if they catch the flu, such as pregnant women, children under 59 months, the elderly, and people with [[chronic illness]]es or [[immunosuppression|weakened immune systems]], as well as those to whom they are exposed, such as health care workers.<ref name="WhoShouldVax"/><ref name="WHO Fact Sheet">{{cite web | title=Influenza (Seasonal) | website=[[World Health Organization]] (WHO) | date=November 6, 2018 | url=https://www.who.int/en/news-room/fact-sheets/detail/influenza-(seasonal) | archive-url=https://web.archive.org/web/20191025024946/https://www.who.int/en/news-room/fact-sheets/detail/influenza-(seasonal) | archive-date=October 25, 2019 | url-status=live | access-date=October 24, 2019}}</ref>

There is a high-dose flu vaccine specifically formulated to provide a stronger immune response.<ref>{{cite web |url=http://www.sciencebasedmedicine.org/index.php/high-dose-flu-vaccine-for-the-elderly/ |title=High Dose Flu Vaccine for the Elderly « Science-Based Medicine |date=October 19, 2010 |publisher=Sciencebasedmedicine.org |access-date=October 17, 2013 |url-status=live |archive-url=https://web.archive.org/web/20130508081643/http://www.sciencebasedmedicine.org/index.php/high-dose-flu-vaccine-for-the-elderly/ |archive-date=May 8, 2013 }}</ref> Available evidence indicates that vaccinating the elderly with the high-dose vaccine leads to a stronger immune response against influenza than the regular-dose vaccine.<ref>{{cite web |url=https://www.cdc.gov/flu/prevent/qa_fluzone.htm |title=Fluzone High-Dose Seasonal Influenza Vaccine |publisher=U.S. [[Centers for Disease Control and Prevention]] (CDC) |date=September 6, 2019 |archive-url=https://web.archive.org/web/20191202211420/https://www.cdc.gov/flu/prevent/qa_fluzone.htm | archive-date=December 2, 2019 | url-status=live | access-date=December 2, 2019}}</ref><ref>{{cite journal | vauthors = DiazGranados CA, Dunning AJ, Kimmel M, Kirby D, Treanor J, Collins A, Pollak R, Christoff J, Earl J, Landolfi V, Martin E, Gurunathan S, Nathan R, Greenberg DP, Tornieporth NG, Decker MD, Talbot HK | title = Efficacy of high-dose versus standard-dose influenza vaccine in older adults | journal = The New England Journal of Medicine | volume = 371 | issue = 7 | pages = 635–45 | date = August 2014 | pmid = 25119609 | doi = 10.1056/NEJMoa1315727 | s2cid = 205096393 | doi-access = free }}</ref><ref>{{cite journal | title = High Dose Influenza Vaccine for Adults: A Review of Clinical Effectiveness, Cost-Effectiveness, and Guidelines | journal = Rapid Response Report | date = January 8, 2019 | vauthors = Wells C, Grobelna A | issn = 1922-8147 | url = https://cadth.ca/sites/default/files/pdf/htis/2018/RC1059%20High%20Dose%20Flu%20Vaccine%20Final.pdf | publisher = Canadian Agency for Drugs and Technologies in Health (CADTH) | location = Ottawa | pmid = 31141324 | access-date = August 15, 2022 | archive-date = August 1, 2020 | archive-url = https://web.archive.org/web/20200801200034/https://cadth.ca/sites/default/files/pdf/htis/2018/RC1059%20High%20Dose%20Flu%20Vaccine%20Final.pdf | url-status = live }}</ref>

A flu vaccine containing an [[adjuvant]] was approved by the US [[Food and Drug Administration]] (FDA) in November 2015, for use by adults aged 65 years of age and older. The vaccine is marketed as Fluad in the US and was first available in the 2016–2017 flu season. The vaccine contains the [[MF59|MF59C.1 adjuvant]]<ref>{{cite journal | vauthors = Mascagni P, Vicenzi E, Kajaste-Rudnitski A, Pellicciotta G, Monti A, Cervi C, Vitalucci R, Toffoletto F | title = Assessment of efficacy and safety of pandemic A/H1N1/2009 influenza vaccine in a group of health care workers | journal = La Medicina del Lavoro | volume = 103 | issue = 3 | pages = 220–29 | year = 2012 | pmid = 22838300 }}</ref> which is an oil-in-water emulsion of [[squalene]] oil. It is the first adjuvanted seasonal flu vaccine marketed in the United States.<ref>{{cite press release |title=FDA approves first seasonal influenza vaccine containing an adjuvant |url=https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm474295.htm |date=November 24, 2015 |publisher=U.S. [[Food and Drug Administration]] (FDA) |access-date=August 20, 2017 |archive-url=https://web.archive.org/web/20170722061508/https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm474295.htm |archive-date=July 22, 2017 }} {{PD-notice}}</ref><ref name="CDC Adjuvant" /><ref>{{cite web | title=Fluad | publisher=U.S. [[Food and Drug Administration]] (FDA) | date=November 8, 2019 | url=https://www.fda.gov/vaccines-blood-biologics/vaccines/fluad | archive-url=https://web.archive.org/web/20191202210615/https://www.fda.gov/vaccines-blood-biologics/vaccines/fluad | archive-date=December 2, 2019 | url-status=live | access-date=December 2, 2019 | id=STN 125510}} {{PD-notice}}</ref> It is not clear if there is a significant benefit for the elderly to use a flu vaccine containing the MF59C.1 adjuvant.<ref>{{cite journal | title = Influenza vaccine with squalene adjuvant: new preparation. No better than available products | journal = Prescrire International | volume = 13 | issue = 74 | pages = 206–08 | date = December 2004 | pmid = 15599987 }}</ref><ref>{{cite journal | vauthors = Camilloni B, Basileo M, Valente S, Nunzi E, Iorio AM | title = Immunogenicity of intramuscular MF59-adjuvanted and intradermal administered influenza enhanced vaccines in subjects aged over 60: A literature review | journal = Human Vaccines & Immunotherapeutics | volume = 11 | issue = 3 | pages = 553–63 | year = 2015 | pmid = 25714138 | pmc = 4514405 | doi = 10.1080/21645515.2015.1011562}}

*{{lay source |template=cite web |date=May 1, 2018 |title=Literature Review Update on the Efficacy and Effectiveness of High-Dose (Fluzone High-Dose) and MF59-Adjuvanted (Fluad) Trivalent Inactivated Influenza Vaccines in Adults 65 Years of Age and Older |website=Public Health Agency of Canada |url=https://www.canada.ca/en/public-health/services/publications/healthy-living/executive-summary-literature-review-update-efficacy-effectiveness-fluzone-high-dose-fluad-trivalent-inactivated-influenza-vaccines-adults-65-older.html }}</ref><ref>{{cite journal | vauthors = Van Damme P, Arnou R, Kafeja F, Fiquet A, Richard P, Thomas S, Meghlaoui G, Samson SI, Ledesma E | title = Evaluation of non-inferiority of intradermal versus adjuvanted seasonal influenza vaccine using two serological techniques: a randomised comparative study | journal = BMC Infectious Diseases | volume = 10 | page = 134 | date = May 2010 | pmid = 20504306 | pmc = 2895601 | doi = 10.1186/1471-2334-10-134 | doi-access = free }}</ref> Per [[Advisory Committee on Immunization Practices]] guidelines, Fluad can be used as an alternative to other influenza vaccines approved for people 65 years and older.<ref name="CDC Adjuvant">{{cite web | title=Flu Vaccine With Adjuvant | website=U.S. [[Centers for Disease Control and Prevention]] (CDC) | date=September 4, 2019 | url=https://www.cdc.gov/flu/prevent/adjuvant.htm | archive-url=https://web.archive.org/web/20191202210120/https://www.cdc.gov/flu/prevent/adjuvant.htm | archive-date=December 2, 2019 | url-status=live | access-date=December 2, 2019}} {{PD-notice}}</ref>

The trivalent inactivated influenza vaccine is protective in pregnant women infected with [[HIV/AIDS|HIV]].<ref name="MadhiCutland2014">{{cite journal | vauthors = Madhi SA, Cutland CL, Kuwanda L, Weinberg A, Hugo A, Jones S, Adrian PV, van Niekerk N, Treurnicht F, Ortiz JR, Venter M, Violari A, Neuzil KM, Simões EA, Klugman KP, Nunes MC | title = Influenza vaccination of pregnant women and protection of their infants | journal = The New England Journal of Medicine | volume = 371 | issue = 10 | pages = 918–31 | date = September 2014 | pmid = 25184864 | doi = 10.1056/NEJMoa1401480 | hdl = 2263/42412 | hdl-access=free }}</ref>

Contrary to a [[List of common misconceptions|common misconception]], flu shots cannot cause people to get the flu.<ref>{{Cite news |last vauthors = McNeil Jr |first=Donald GDG |date=October 1, 2018 |title=Over 80,000 Americans Died of Flu Last Winter, Highest Toll in Years |url=https://www.nytimes.com/2018/10/01/health/flu-deaths-vaccine.html |url-status=live |archive-url=https://web.archive.org/web/20181001182236/https://www.nytimes.com/2018/10/01/health/flu-deaths-vaccine.html |archive-date=October 1, 2018 |access-date=June 24, 2024 |work=[[The New York Times]]}}</ref><ref>{{Cite web |title=5 myths about the flu vaccine |url=https://www.who.int/news-room/spotlight/influenza-are-we-ready/5-myths-about-the-flu-vaccine |url-status=live |archive-url=https://web.archive.org/web/20240214132129/https://www.who.int/news-room/spotlight/influenza-are-we-ready/5-myths-about-the-flu-vaccine |archive-date=February 14, 2024 |access-date=June 24, 2024 |website=[[World Health Organization]]}}</ref>

Although [[Guillain–Barré syndrome]] had been feared as a complication of vaccination, the CDC states that most studies on modern influenza vaccines have seen no link with Guillain–Barré.<ref>{{cite journal | vauthors = Haber P, Sejvar J, Mikaeloff Y, DeStefano F | title = Vaccines and Guillain-Barré syndrome | journal = Drug Safety | volume = 32 | issue = 4 | pages = 309–23 | year = 2009 | pmid = 19388722 | doi = 10.2165/00002018-200932040-00005 | s2cid = 33670594 }}</ref><ref>{{cite journal | title = Reorganized text | journal = JAMA Otolaryngology–Head & Neck Surgery | volume = 141 | issue = 5 | page = 428 | date = May 2015 | pmid = 25996397 | doi = 10.1001/jamaoto.2015.0540 | s2cid = 26612829 }}</ref> Infection with influenza virus itself increases both the risk of death (up to one in ten thousand) and the risk of developing Guillain–Barré syndrome to a far higher level than the highest level of suspected vaccine involvement (approximately ten times higher by 2009 estimates).<ref>{{cite journal | vauthors = Stowe J, Andrews N, Wise L, Miller E | title = Investigation of the temporal association of Guillain-Barre syndrome with influenza vaccine and influenza-like illness using the United Kingdom General Practice Research Database | journal = American Journal of Epidemiology | volume = 169 | issue = 3 | pages = 382–88 | date = February 2009 | pmid = 19033158 | doi = 10.1093/aje/kwn310 | doi-access = free | title-link = doi }}</ref><ref name="ReferenceB">{{cite journal | vauthors = Sivadon-Tardy V, Orlikowski D, Porcher R, Sharshar T, Durand MC, Enouf V, Rozenberg F, Caudie C, Annane D, van der Werf S, Lebon P, Raphaël JC, Gaillard JL, Gault E | title = Guillain-Barré syndrome and influenza virus infection | journal = Clinical Infectious Diseases | volume = 48 | issue = 1 | pages = 48–56 | date = January 2009 | pmid = 19025491 | doi = 10.1086/594124 | doi-access = free | title-link = doi }}</ref>

Although most influenza vaccines are produced using egg-based techniques, influenza vaccines are nonetheless still recommended as safe for people with [[egg allergy|egg allergies]], even if severe,<ref name="CDCegg"/> as no increased risk of allergic reaction to the egg-based vaccines has been shown for people with egg allergies.<ref name="cell2021">{{cite news |date=March 27, 2021 |title=Australia's first cell-based influenza vaccines to roll out this flu season |website=ABC News |url=https://www.abc.net.au/news/health/2021-03-27/flu-new-vaccine-cell-based-australian-first/100023908 |url-status=live |access-date=April 28, 2021 |archive-url=https://web.archive.org/web/20210427180254/https://www.abc.net.au/news/health/2021-03-27/flu-new-vaccine-cell-based-australian-first/100023908 |archive-date=April 27, 2021 |vauthors=Roberts L}}</ref> Studies examining the safety of influenza vaccines in people with severe egg allergies found that [[anaphylaxis]] was very rare, occurring in 1.3 cases per million doses given.<ref name="CDCegg"/>

* a nasal spray of [[live attenuated influenza vaccine]] (LAIV, Q/LAIV), which contains the live but attenuated (weakened) form of the virus.

In the United States routine influenza vaccination is recommended for all persons aged six months and over.<ref>{{cite journal | vauthors = Grohskopf LA, Ferdinands JM, Blanton LH, Broder KR, Loehr J | title = Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices — United States, 2024–25 Influenza Season | journal = MMWR. Recommendations and Reports | volume=73 | issue=5 | date = August 2024 | pmid = 39197095 | doi = 10.15585/mmwr.rr7305a1 | doi-access = free | pages = 1–25 | pmc = 11501009 | url = <!-- Official URL --> https://www.cdc.gov/mmwr/volumes/73/rr/pdfs/rr7305a1-H.pdf }}</ref><ref name="pmid34448800">{{cite journal |vauthors=Grohskopf LA, Alyanak E, Ferdinands JM, Broder KR, Blanton LH, Talbot HK, Fry AM |title=Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices, United States, 2021-22 Influenza Season |journal=MMWR Recomm Rep |volume=70 |issue=5 |pages=1–28 |date=August 2021 |pmid=34448800 |doi=10.15585/mmwr.rr7005a1 |pmc=8407757 |doi-access=free |title-link=doi |url=<!-- Official URL --> https://www.cdc.gov/mmwr/volumes/70/rr/pdfs/rr7005a1-H.pdf |access-date=August 29, 2021 |archive-date=August 27, 2021 |archive-url=https://web.archive.org/web/20210827010217/https://www.cdc.gov/mmwr/volumes/70/rr/pdfs/rr7005a1-H.pdf |url-status=live }} {{PD-notice}}</ref><ref name="ReferenceA">{{cite web|url=https://www.cdc.gov/flu/highrisk/children.htm|title=Children & Influenza (Flu)|publisher=U.S. [[Centers for Disease Control and Prevention]] (CDC)|date=October 23, 2019|url-status=live|archive-url=https://web.archive.org/web/20191111042856/https://www.cdc.gov/flu/highrisk/children.htm|archive-date=November 11, 2019}} {{PD-notice}}</ref> It takes up to two weeks after vaccination for sufficient antibodies to develop in the body.<ref name="ReferenceA" /> The CDC recommends vaccination before the end of October,<ref name="pmid34448800" /> although it considers getting a vaccine in December or even later to be still beneficial.<ref name="pmid34448800" /><ref name="CDC Facts"/><ref name="ReferenceA" /> The [[United States Armed Forces|U.S. military]] also requires a flu shot annually for its active and reserve servicemembers.<ref>{{Cite news |last=Rahman |first=Khaleda |date=October 21, 2021 |title=Full List of Vaccines Mandated by the U.S. Military |url=https://www.newsweek.com/list-vaccines-mandated-us-military-covid-1641228 |url-status=live |archive-url=https://web.archive.org/web/20231219004334/https://www.newsweek.com/list-vaccines-mandated-us-military-covid-1641228 |archive-date=December 19, 2023 |work=[[Newsweek]]}}</ref>

:Vaccination is especially important for people at higher risk of serious influenza complications or people who live with or care for people at higher risk for serious complications.<ref>{{cite web|url=https://www.cdc.gov/flu/professionals/vaccination/vax-summary.htm|title=Influenza Vaccination: A Summary for Clinicians – Health Professionals – Seasonal Influenza (Flu)|publisher=U.S. [[Centers for Disease Control and Prevention]] (CDC)|url-status=live|archive-url=https://web.archive.org/web/20080224040716/http://www.cdc.gov/flu/professionals/vaccination/vax-summary.htm|archive-date=February 24, 2008|date=September 6, 2018}} {{PD-notice}}</ref> In 2009, a new high-dose formulation of the standard influenza vaccine was approved.<ref>{{cite web | title=Fluzone, Fluzone High-Dose and Fluzone Intradermal | publisher=U.S. [[Food and Drug Administration]] (FDA) | url=https://www.fda.gov/vaccines-blood-biologics/vaccines/fluzone-fluzone-high-dose-and-fluzone-intradermal | date=July 11, 2017 | archive-date=July 22, 2017 | archive-url=https://wayback.archive-it.org/7993/20170722071642/https://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm112854.htm | url-status=live | access-date=June 1, 2020}}</ref> The Fluzone High Dose is specifically for people 65 and older; the difference is that it has four times the antigen dose of the standard Fluzone.<ref>{{cite journal | vauthors = Couch RB, Winokur P, Brady R, Belshe R, Chen WH, Cate TR, Sigurdardottir B, Hoeper A, Graham IL, Edelman R, He F, Nino D, Capellan J, Ruben FL | title = Safety and immunogenicity of a high dosage trivalent influenza vaccine among elderly subjects | journal = Vaccine | volume = 25 | issue = 44 | pages = 7656–63 | date = November 2007 | pmid = 17913310 | pmc = 2243220 | doi = 10.1016/j.vaccine.2007.08.042 }}</ref><ref>{{cite journal |vauthors=Lee JK, Lam GK, Shin T, Kim J, Krishnan A, Greenberg DP, Chit A |title=Efficacy and effectiveness of high-dose versus standard-dose influenza vaccination for older adults: a systematic review and meta-analysis |journal=Expert Rev Vaccines |volume=17 |issue=5 |pages=435–443 |date=May 2018 |pmid=29715054 |doi=10.1080/14760584.2018.1471989 | s2cid=21688517 }}</ref><ref>{{cite journal |vauthors=Robertson CA, DiazGranados CA, Decker MD, Chit A, Mercer M, Greenberg DP |title=Fluzone High-Dose Influenza Vaccine |journal=Expert Rev Vaccines |volume=15 |issue=12 |pages=1495–1505 |date=December 2016 |pmid=27813430 |doi=10.1080/14760584.2016.1254044 | doi-access = free | title-link = doi }}</ref><ref>{{cite report |title=Literature review update on the efficacy and effectiveness of high-dose (Fluzone High-Dose) and MF59-adjuvanted (Fluad) trivalent inactivated influenza vaccines in adults 65 years of age and older |id=HP40-210/2018E-PDF |location=Ottawa |publisher=Public Health Agency of Canada |date=May 2018 |url=http://publications.gc.ca/collections/collection_2018/aspc-phac/HP40-210-2018-eng.pdf |access-date=June 1, 2020 |archive-date=July 21, 2020 |archive-url=https://web.archive.org/web/20200721210629/http://publications.gc.ca/collections/collection_2018/aspc-phac/HP40-210-2018-eng.pdf |url-status=live }}</ref>

Frontline health care workers are often recommended to get seasonal and any pandemic flu vaccination. For example, in the UK all health care workers involved in patient care are recommended to receive the seasonal flu vaccine, and were also recommended to be vaccinated against the [[Pandemic H1N1/09 virus|H1N1/09]] (later renamed A(H1N1)pdm09<ref name="pdm09" group="note">(H1N1)pdm09 is newer nomenclature for the 2009 pandemic H1N1 virus, not a different strain.</ref><ref name="2009 Composition">{{cite journal | title = Update on influenza A (H1N1) 2009 monovalent vaccines | journal = Morbidity and Mortality Weekly Report (MMWR)| volume = 58 | issue = 39 | pages = 1100–01 | date = October 2009 | pmid = 19816398 | url = https://www.cdc.gov/mmwr/pdf/wk/mm5839.pdf | archive-url = https://web.archive.org/web/20110629132344/http://www.cdc.gov/mmwr/pdf/wk/mm5839.pdf | url-status = live | archive-date = June 29, 2011 |author=Centers for Disease Control Prevention (CDC)}} {{PD-notice}}</ref>) swine flu virus during the [[2009 flu pandemic|2009 pandemic]]. However, uptake is often low.<ref name=Rubin>{{cite journal | vauthors = Rubin GJ, Potts HW, Michie S | title = Likely uptake of swine and seasonal flu vaccines among healthcare workers. A cross-sectional analysis of UK telephone survey data | journal = Vaccine | volume = 29 | issue = 13 | pages = 2421–28 | date = March 2011 | pmid = 21277402 | doi = 10.1016/j.vaccine.2011.01.035 }}</ref> During the 2009 pandemic, low uptake by healthcare workers was seen in countries including the UK,<ref name=Rubin /> Italy,<ref>{{cite journal | vauthors = La Torre G, Di Thiene D, Cadeddu C, Ricciardi W, Boccia A | title = Behaviours regarding preventive measures against pandemic H1N1 influenza among Italian healthcare workers, October 2009 | journal = Euro Surveillance | volume = 14 | issue = 49 | date = December 2009 | pmid = 20003908 }}</ref> Greece,<ref>{{cite journal | vauthors = Amodio E, Anastasi G, Marsala MG, Torregrossa MV, Romano N, Firenze A | title = Vaccination against the 2009 pandemic influenza A (H1N1) among healthcare workers in the major teaching hospital of Sicily (Italy) | journal = Vaccine | volume = 29 | issue = 7 | pages = 1408–12 | date = February 2011 | pmid = 21199700 | doi = 10.1016/j.vaccine.2010.12.041 }}</ref> and Hong Kong.<ref>{{cite journal | vauthors = Chor JS, Ngai KL, Goggins WB, Wong MC, Wong SY, Lee N, Leung TF, Rainer TH, Griffiths S, Chan PK | title = Willingness of Hong Kong healthcare workers to accept pre-pandemic influenza vaccination at different WHO alert levels: two questionnaire surveys | journal = BMJ | volume = 339 | page = b3391 | date = August 2009 | pmid = 19706937 | pmc = 2731837 | doi = 10.1136/bmj.b3391 }}</ref>

Research continues into the idea of a [[Universal flu vaccine|"universal" influenza vaccine]] that would not require tailoring to a particular strain, but would be effective against a broad variety of influenza viruses.<ref name="pmid31693060">{{cite journal | vauthors = Abbasi J | title = The Search for a Universal Flu Vaccine Heats Up | journal = JAMA | volume = 322 | issue = 20 | pages = 1942–1944 | date = November 2019 | pmid = 31693060 | doi = 10.1001/jama.2019.16816 | s2cid = 207903441 }}</ref> No vaccine candidates had been announced by November 2007,<ref name=NPR2007>{{cite AV media | vauthors = Greenfieldboyce N | title=New and Old Ways to Make Flu Vaccines | publisher=[[NPR]] | date=November 8, 2007 | url=https://www.npr.org/templates/story/story.php?storyId=16105360 | archive-url=https://web.archive.org/web/20191024052018/https://www.npr.org/templates/story/story.php?storyId=16105360 | archive-date=October 24, 2019 | url-status=live | access-date=October 23, 2019 | medium=Radio broadcast }}</ref> but {{as of|lc=yes|2021}}, there are several universal vaccines candidates, in pre-clinical development and in clinical trials.<ref name= "Nachbagauer_2017">{{cite journal | vauthors = Nachbagauer R, Krammer F | title = Universal influenza virus vaccines and therapeutic antibodies | journal = Clinical Microbiology and Infection | volume = 23 | issue = 4 | pages = 222–228 | date = April 2017 | pmid = 28216325 | pmc = 5389886 | doi = 10.1016/j.cmi.2017.02.009 }}</ref><ref>{{Cite web |title=First-in-human universal flu vaccine trial begins |vauthors=Balfour H |website=European Pharmaceutical Review |date=June 2, 2021 |url=https://www.europeanpharmaceuticalreview.com/news/155806/first-in-human-universal-flu-vaccine-trial-begins/ |quote=The Phase I trial (NCT04896086) will assess the safety and immunogenicity of the experimental vaccine, FluMos-v1 |access-date=February 6, 2022 |archive-date=March 29, 2022 |archive-url=https://web.archive.org/web/20220329214713/https://www.europeanpharmaceuticalreview.com/news/155806/first-in-human-universal-flu-vaccine-trial-begins/ |url-status=live }}</ref><ref>{{cite journal | vauthors = Bernstein DI, Guptill J, Naficy A, Nachbagauer R, Berlanda-Scorza F, Feser J, Wilson PC, Solórzano A, Van der Wielen M, Walter EB, Albrecht RA, Buschle KN, Chen YQ, Claeys C, Dickey M, Dugan HL, Ermler ME, Freeman D, Gao M, Gast C, Guthmiller JJ, Hai R, Henry C, Lan LY, McNeal M, Palm AE, Shaw DG, Stamper CT, Sun W, Sutton V, Tepora ME, Wahid R, Wenzel H, Wohlbold TJ, Innis BL, García-Sastre A, Palese P, Krammer F | title = Immunogenicity of chimeric haemagglutinin-based, universal influenza virus vaccine candidates: interim results of a randomised, placebo-controlled, phase 1 clinical trial | journal = The Lancet. Infectious Diseases | volume = 20 | issue = 1 | pages = 80–91 | date = January 2020 | pmid = 31630990 | pmc = 6928577 | doi = 10.1016/S1473-3099(19)30393-7 | doi-access = free | title-link = doi }}</ref><ref>{{cite journal | vauthors = Nachbagauer R, Feser J, Naficy A, Bernstein DI, Guptill J, Walter EB, Berlanda-Scorza F, Stadlbauer D, Wilson PC, Aydillo T, Behzadi MA, Bhavsar D, Bliss C, Capuano C, Carreño JM, Chromikova V, Claeys C, Coughlan L, Freyn AW, Gast C, Javier A, Jiang K, Mariottini C, McMahon M, McNeal M, Solórzano A, Strohmeier S, Sun W, Van der Wielen M, Innis BL, García-Sastre A, Palese P, Krammer F | title = A chimeric hemagglutinin-based universal influenza virus vaccine approach induces broad and long-lasting immunity in a randomized, placebo-controlled phase I trial | journal = Nature Medicine | volume = 27 | issue = 1 | pages = 106–114 | date = January 2021 | pmid = 33288923 | doi = 10.1038/s41591-020-1118-7 | doi-access = free | title-link = doi }}</ref>

After the 48-hour incubation period, the top of the egg is cracked and the ten milliliters of allantoic fluid is removed, from which about fifteen micrograms of the flu vaccine can be obtained. At this point, the viruses have been weakened or killed and the viral antigen is purified and placed inside vials, syringes, or nasal sprayers.<ref name="cdc.gov"/> Up to 3 eggs are needed to produce one dose of a trivalent vaccine, and an estimated 600 million eggs are produced each year for flu vaccine production.<ref>{{Cite web |vauthors=Seemann G, Kock M |date=2008 |title=Fertile eggs – a valuable product for vaccine production |url=https://lohmann-breeders.com/lohmanninfo/fertile-eggs-a-valuable-product-for-vaccine-production/ |access-date=October 19, 2023 |website=Lohmann Breeders |language=en-US |archive-date=November 23, 2023 |archive-url=https://web.archive.org/web/20231123222125/https://lohmann-breeders.com/lohmanninfo/fertile-eggs-a-valuable-product-for-vaccine-production/ |url-status=live }}</ref>

Methods of vaccine generation that bypass the need for eggs include the construction of influenza [[virus-like particle]]s (VLP). VLP resemble viruses, but there is no need for inactivation, as they do not include viral coding elements, but merely present antigens in a similar manner to a virion. Some methods of producing VLP include cultures of ''[[Spodoptera frugiperda]]'' [[Sf21|Sf9 insect cells]] and plant-based vaccine production (e.g., production in ''[[Nicotiana benthamiana]]''). There is evidence that some VLPs elicit antibodies that recognize a broader panel of antigenically distinct viral isolates compared to other vaccines in the [[hemagglutination-inhibition assay]] (HIA).<ref>{{cite journal | vauthors = Bright RA, Carter DM, Daniluk S, Toapanta FR, Ahmad A, Gavrilov V, Massare M, Pushko P, Mytle N, Rowe T, Smith G, Ross TM | title = Influenza virus-like particles elicit broader immune responses than whole virion inactivated influenza virus or recombinant hemagglutinin | journal = Vaccine | volume = 25 | issue = 19 | pages = 3871–78 | date = May 2007 | pmid = 17337102 | doi = 10.1016/j.vaccine.2007.01.106 }}</ref>

OnIn November 20, 2012, Novartis received FDA approval for the first cell-culture vaccine.<ref name=novartiscell>{{cite press release|url=https://www.prnewswire.com/news-releases/novartis-receives-fda-approval-for-flucelvax-the-first-cell-culture-vaccine-in-us-to-help-protect-against-seasonal-influenza-180239401.html |archive-url=https://web.archive.org/web/20121128072149/http://www.novartis.com/newsroom/media-releases/en/2012/1659272.shtml |url-status=live |archive-date=November 28, 2012 |title=Novartis receives FDA approval for Flucelvax, the first cell-culture vaccine in US to help protect against seasonal influenza |publisher=Novartis |date=November 20, 2012 }}</ref><ref name="FDA Flucelvax PR">{{cite press release|url=https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm328982.htm|title=FDA approves first seasonal influenza vaccine manufactured using cell culture technology|publisher=U.S. [[Food and Drug Administration]] (FDA)|archive-url=https://web.archive.org/web/20130102094936/https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm328982.htm|archive-date=January 2, 2013}} {{PD-notice}}</ref><ref>{{cite web|url=https://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm328684.htm|title=Approved Products – November 20, 2012 Approval Letter – Flucelvax| author = Center for Biologics Evaluation and Research |publisher=U.S. [[Food and Drug Administration]] (FDA)|archive-url=https://web.archive.org/web/20121203114226/https://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm328684.htm|archive-date=December 3, 2012}} {{PD-notice}}</ref><ref>{{cite press release | title = Seqirus receives FDA approval for Flucelvax Quadrivalent (Influenza Vaccine) for people four years of age and older | url = http://www.seqirus.com/newsroom/FDA-approval-FLUCELVAX-QUADRIVALENT | publisher = [[CSL Limited|Seqirus]] | date = May 23, 2016 | archive-url = https://web.archive.org/web/20170116163927/http://www.seqirus.com/newsroom/FDA-approval-FLUCELVAX-QUADRIVALENT | archive-date = January 16, 2017 | access-date = January 15, 2017 }}</ref> In 2013, the recombinant influenza vaccine, Flublok, was approved for use in the United States.<ref name="FDA Flublok PR" /><ref>{{cite web | title=FDA approves first flu vaccine grown in insect cells | vauthors = Roos R | website=[[Center for Infectious Disease Research and Policy]] (CIDRAP) | date=October 14, 2019 | url=http://www.cidrap.umn.edu/news-perspective/2013/01/fda-approves-first-flu-vaccine-grown-insect-cells | archive-url=https://web.archive.org/web/20191014200136/http://www.cidrap.umn.edu/news-perspective/2013/01/fda-approves-first-flu-vaccine-grown-insect-cells | archive-date=October 14, 2019 | url-status=live | access-date=October 14, 2019 }}</ref><ref>{{cite web | title=Flublok | publisher= U.S. [[Food and Drug Administration]] (FDA) | date=February 26, 2018 | url=https://www.fda.gov/vaccines-blood-biologics/vaccines/flublok | archive-url=https://web.archive.org/web/20191014200957/https://www.fda.gov/vaccines-blood-biologics/vaccines/flublok | archive-date=October 14, 2019 | url-status=live | access-date=October 14, 2019 | id= STN 125285}} {{PD-notice}}</ref><ref>{{cite web | title=Flublok Quadrivalent | publisher= U.S. [[Food and Drug Administration]] (FDA) | date=August 2, 2019 | url=https://www.fda.gov/vaccines-blood-biologics/vaccines/flublok-quadrivalent | archive-url=https://web.archive.org/web/20191014201325/https://www.fda.gov/vaccines-blood-biologics/vaccines/flublok-quadrivalent | archive-date=October 14, 2019 | url-status=live | access-date=October 14, 2019 | id= STN 125285}} {{PD-notice}}</ref>

On September 17, 2020, the [[Committee for Medicinal Products for Human Use]] (CHMP) of the [[European Medicines Agency]] (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for Supemtek, a quadrivalent influenza vaccine (recombinant, prepared in cell culture).<ref name="Supemtek: Pending EC decision">{{cite web | title=Supemtek: Pending EC decision | website=[[European Medicines Agency]] (EMA) | date=September 17, 2020 | url=https://www.ema.europa.eu/en/medicines/human/summaries-opinion/supemtek | access-date=September 21, 2020 | archive-date=September 23, 2020 | archive-url=https://web.archive.org/web/20200923005908/https://www.ema.europa.eu/en/medicines/human/summaries-opinion/supemtek | url-status=live }} Text was copied from this source which is ©copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref> The applicant for this medicinal product is Sanofi Pasteur.<ref name="Supemtek: Pending EC decision" /> Supemtek was approved for medical use in the European Union in November 2020.<ref name="Supemtek EPAR">{{cite web | title=Supemtek EPAR | website=[[European Medicines Agency]] (EMA) | date=September 15, 2020 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/supemtek | access-date=November 27, 2020 | archive-date=January 10, 2021 | archive-url=https://web.archive.org/web/20210110092717/https://www.ema.europa.eu/en/medicines/human/EPAR/supemtek | url-status=live }}</ref><ref>{{cite web | title=Supemtek Product information | website=Union Register of medicinal products | url=https://ec.europa.eu/health/documents/community-register/html/h1484.htm | access-date=March 3, 2023 | archive-date=March 5, 2023 | archive-url=https://web.archive.org/web/20230305052137/https://ec.europa.eu/health/documents/community-register/html/h1484.htm | url-status=live }}</ref>

The cost-effectiveness of seasonal influenza vaccination has been widely evaluated for different groups and in different settings.<ref>{{cite journal | vauthors = Jit M, Newall AT, Beutels P | title = Key issues for estimating the impact and cost-effectiveness of seasonal influenza vaccination strategies | journal = Human Vaccines & Immunotherapeutics | volume = 9 | issue = 4 | pages = 834–40 | date = April 2013 | pmid = 23357859 | pmc = 3903903 | doi = 10.4161/hv.23637 }}</ref> In the elderly (over 65), the majority of published studies have found that vaccination is cost saving, with the cost savings associated with influenza vaccination (e.g. prevented health care visits) outweighing the cost of vaccination.<ref>{{cite journal | vauthors = Postma MJ, Baltussen RP, Palache AM, Wilschut JC | title = Further evidence for favorable cost-effectiveness of elderly influenza vaccination | journal = Expert Review of Pharmacoeconomics & Outcomes Research | volume = 6 | issue = 2 | pages = 215–27 | date = April 2006 | pmid = 20528557 | doi = 10.1586/14737167.6.2.215 | s2cid = 12765724 }}</ref> In older adults (aged 50–64 years), several published studies have found that influenza vaccination is likely to be cost-effective, however the results of these studies were often found to be dependent on key assumptions used in the economic evaluations.<ref>{{cite journal | vauthors = Newall AT, Kelly H, Harsley S, Scuffham PA | title = Cost effectiveness of influenza vaccination in older adults: a critical review of economic evaluations for the 50- to 64-year age group | journal = PharmacoEconomics | volume = 27 | issue = 6 | pages = 439–50 | year = 2009 | pmid = 19640008 | doi = 10.2165/00019053-200927060-00001 | s2cid = 20855671 | doi-access = free }}</ref> The uncertainty in influenza cost-effectiveness models can partially be explained by the complexities involved in estimating the disease burden,<ref>{{cite journal | vauthors = Newall AT, Viboud C, Wood JG | title = Influenza-attributable mortality in Australians aged more than 50 years: a comparison of different modelling approaches | journal = Epidemiology and Infection | volume = 138 | issue = 6 | pages = 836–42 | date = June 2010 | pmid = 19941685 | doi = 10.1017/S095026880999118X | s2cid = 29939376 | doi-access = free }}</ref> as well as the seasonal variability in the circulating strains and the match of the vaccine.<ref>{{cite journal | vauthors = Newall AT, Dehollain JP, Creighton P, Beutels P, Wood JG | title = Understanding the cost-effectiveness of influenza vaccination in children: methodological choices and seasonal variability | journal = PharmacoEconomics | volume = 31 | issue = 8 | pages = 693–702 | date = August 2013 | pmid = 23645539 | doi = 10.1007/s40273-013-0060-7 | s2cid = 8616720 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Newall AT, Scuffham PA | title = Uncertainty and variability in influenza cost-effectiveness models | journal = Australian and New Zealand Journal of Public Health | volume = 35 | issue = 6 | pages = 576; author reply 576–77 | date = December 2011 | pmid = 22151168 | doi = 10.1111/j.1753-6405.2011.00788.x | s2cid = 22402257 | doi-access = | title-link = doi }}</ref> In healthy working adults (aged 18–49 years), a 2012 review found that vaccination was generally not cost-saving, with the suitability for funding being dependent on the willingness to pay to obtain the associated health benefits.<ref>{{cite journal | vauthors = Gatwood J, Meltzer MI, Messonnier M, Ortega-Sanchez IR, Balkrishnan R, Prosser LA | title = Seasonal influenza vaccination of healthy working-age adults: a review of economic evaluations | journal = Drugs | volume = 72 | issue = 1 | pages = 35–48 | date = January 2012 | pmid = 22191794 | doi = 10.2165/11597310-000000000-00000 | s2cid = 46305863 }}</ref> In children, the majority of studies have found that influenza vaccination was cost-effective, however many of the studies included (indirect) productivity gains, which may not be given the same weight in all settings.<ref>{{cite journal | vauthors = Newall AT, Jit M, Beutels P | title = Economic evaluations of childhood influenza vaccination: a critical review | journal = PharmacoEconomics | volume = 30 | issue = 8 | pages = 647–60 | date = August 2012 | pmid = 22788257 | doi = 10.2165/11599130-000000000-00000 | s2cid = 38289883 | doi-access = free }}</ref> Several studies have attempted to predict the cost-effectiveness of interventions (including prepandemic vaccination) to help protect against a future pandemic, however estimating the cost-effectiveness has been complicated by uncertainty as to the severity of a potential future pandemic and the efficacy of measures against it.<ref>{{cite journal | vauthors = Newall AT, Wood JG, Oudin N, MacIntyre CR | title = Cost-effectiveness of pharmaceutical-based pandemic influenza mitigation strategies | journal = Emerging Infectious Diseases | volume = 16 | issue = 2 | pages = 224–30 | date = February 2010 | pmid = 20113551 | pmc = 2957998 | doi = 10.3201/eid1602.090571 }}</ref>

[[Influenza research]] includes [[molecular virology]], [[molecular evolution]], [[pathogenesis]], host [[immune response]]s, [[genomics]], and [[epidemiology]]. These help in developing influenza countermeasures such as [[vaccine]]s, therapies and diagnostic tools. Improved influenza countermeasures require basic research on how viruses enter cells, replicate, mutate, evolve into new strains and induce an immune response. The [[Influenza Genome Sequencing Project]] is creating a library of influenza sequences<ref>{{cite web|title=Influenza Genome Sequencing Project – Overview|url=http://www.niaid.nih.gov/LabsAndResources/resources/dmid/gsc/Influenza/Pages/overview.aspx|archive-url=https://web.archive.org/web/20110627202613/http://www.niaid.nih.gov/LABSANDRESOURCES/RESOURCES/DMID/GSC/INFLUENZA/Pages/overview.aspx|archive-date=June 27, 2011|publisher=National Institutes of Health – National Institute of Allergy and Infectious Diseases|access-date=May 27, 2013}}</ref> that will help researchers' understanding of what makes one strain more lethal than another, what genetic determinants most affect [[immunogenicity]], and how the virus evolves over time. Solutions to limitations in current{{when|date=August 2012}} vaccine methods are being{{when|date=October 2019}} researched.

As of 2019, an oral flu vaccine was in [[clinical research]].<ref>{{cite web|url=https://www.drugtopics.com/vaccination-and-immunization/researchers-exploring-oral-flu-vaccine-and-treatment-options|vauthors=Sederstrom J|title=Researchers Exploring Oral Flu Vaccine and Treatment Options|date=July 19, 2019|access-date=January 27, 2020|publisher=Drug Topics|archive-date=June 8, 2020|archive-url=https://web.archive.org/web/20200608032923/https://www.drugtopics.com/vaccination-and-immunization/researchers-exploring-oral-flu-vaccine-and-treatment-options|url-status=live}}</ref> The oral vaccine candidate is based on an [[adenovirus]] type{{spaces}}5 vector modified to remove genes needed for replication, with an added gene that expresses a small double-stranded [[RNA]] hairpin molecule as an [[adjuvant]].<ref>{{cite journal | vauthors = Jasty M, Bragdon CR, Schutzer S, Rubash H, Haire T, Harris WH | title = Bone ingrowth into porous coated canine total hip replacements. Quantification by backscattered scanning electron microscopy and image analysis | journal = Scanning Microscopy | volume = 3 | issue = 4 | pages = 1051–6; discussion 1056–57 | date = December 1989 | pmid = 2633331 | doi = 10.1016/s1473-3099(15)00252-2 }}</ref> In 2020, [[Phases of clinical research#Phase II|a Phasephase{{spaces}}II human trial]] of the pill form of the vaccine showed that it was well tolerated and provided similar immunity to a licensed [[intramuscular injection|injectable]] vaccine.<ref>{{cite journal | vauthors = Liebowitz D, Gottlieb K, Kolhatkar NS, Garg SJ, Asher JM, Nazareno J, Kim K, McIlwain DR, Tucker SN | title = Efficacy, immunogenicity, and safety of an oral influenza vaccine: a placebo-controlled and active-controlled phase 2 human challenge study | journal = The Lancet. Infectious Diseases | volume = 20 | issue = 4 | pages = 435–444 | date = April 2020 | pmid = 31978354 | doi = 10.1016/S1473-3099(19)30584-5 | publisher = Elsevier | s2cid = 210892802 }}</ref>

An influenza vaccine and a [[COVID-19 vaccine]] may be given safely at the same time.<ref name="NHS28/9/2021">{{cite web | title=Flu vaccine | publisher=UK National Health Service | date=May 13, 2022 | url=https://www.nhs.uk/conditions/vaccinations/flu-influenza-vaccine/ | access-date=August 13, 2022 | archive-date=October 26, 2021 | archive-url=https://web.archive.org/web/20211026210525/https://www.nhs.uk/conditions/vaccinations/flu-influenza-vaccine/ | url-status=live }}</ref><ref>{{cite web | vauthors = Triggle N | title=Flu jab vital this winter along with Covid vaccine | website=BBC News | date=October 8, 2021 | url=https://www.bbc.com/news/health-58836218 | access-date=August 13, 2022 | archive-date=November 14, 2021 | archive-url=https://web.archive.org/web/20211114150601/https://www.bbc.com/news/health-58836218 | url-status=live }}</ref> Preliminary research indicates that influenza vaccination does not prevent [[COVID-19]], but may reduce the incidence and severity of COVID-19 infection.<ref>{{Cite journal | vauthors = Callaway E |date=May 16, 2022 |title=Flu vaccine could cut COVID risk |journal=Nature |language=en |volume=605 |issue=7911 |pages=602 |doi=10.1038/d41586-022-01315-9|pmid=35581411 |bibcode=2022Natur.605..602C |s2cid=248859545 |doi-access=free }}</ref>

In 2004, [[influenza A virus subtype H3N8]] was discovered to cause [[canine influenza]]. Because of the lack of previous exposure to this virus, dogs have no natural immunity to this virus. However, a vaccine was found in 2004.<ref>{{cite journal | vauthors = Karaca K, Dubovi EJ, Siger L, Robles A, Audonnet JC, Jiansheng Y, Nordgren R, Minke JM | title = Evaluation of the ability of canarypox-vectored equine influenza virus vaccines to induce humoral immune responses against canine influenza viruses in dogs | journal = American Journal of Veterinary Research | volume = 68 | issue = 2 | pages = 208–12 | date = February 2007 | pmid = 17269888 | doi = 10.2460/ajvr.68.2.208 }}</ref>

* {{cite book | vauthors = Budd A, Blanton L, Grohskopf L, Campbell A, Dugan V, Wentworth DE, Brammer L | chapter = Chapter 6: Influenza | chapter-url = https://www.cdc.gov/vaccines/pubs/surv-manual/chpt06-influenza.html | veditors = Roush SW, Baldy LM, Hall MA | title = Manual for the surveillance of vaccine-preventable diseases | publisher = U.S. [[Centers for Disease Control and Prevention]] (CDC) | location = Atlanta GA | url = https://www.cdc.gov/vaccines/pubs/surv-manual/ | date = March 29, 2019 | access-date = October 24, 2019 | archive-date = August 1, 2020 | archive-url = https://web.archive.org/web/20200801192220/https://www.cdc.gov/vaccines/pubs/surv-manual/ | url-status = live }}

* {{cite journal |vauthors=Rajaram S, Wojcik R, Moore C, Ortiz de Lejarazu R, de Lusignan S, Montomoli E, Rossi A, Pérez-Rubio A, Trilla A, Baldo V, Jandhyala R, Kassianos G |title=The impact of candidate influenza virus and egg-based manufacture on vaccine effectiveness: Literature review and expert consensus |journal=Vaccine |volume=38 |issue=38 |pages=6047–6056 |date=August 2020 |pmid=32600916 |doi=10.1016/j.vaccine.2020.06.021 | doi-access = free | title-link = doi }}