Influenza vaccines, colloquially known as flu shots or flu jab, are vaccines that protect against infection by influenza viruses. New versions of the vaccines are developed twice a year, as the influenza virus rapidly changes. While their effectiveness varies from year to year, most provide modest to high protection against influenza. Vaccination against influenza began in the 1930s, with large-scale availability in the United States beginning in 1945.
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, and the influenza vaccine is on the World Health Organization's List of Essential Medicines. The European Centre for Disease Prevention and Control (ECDC) also recommends yearly vaccination of high-risk groups, particularly pregnant women, the elderly, children between six months and five years, and those with certain health problems.
The vaccines are generally safe, including for people who have severe egg allergies. 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. Influenza vaccines are not recommended in those who have had a severe allergy to previous versions of the vaccine itself. The vaccine comes in inactive and 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 weakened immune system. Depending on the type it can be injected into a muscle (intramuscular), sprayed into the nose (intranasal), or injected into the middle layer of the skin (intradermal). The intradermal vaccine was not available during the 2018–2019 and 2019–2020 influenza seasons.
History
Vaccines are used in both humans and non-humans. The human vaccine is meant unless specifically identified as a veterinary, poultry, or livestock vaccine.
Origins and development 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 administering oxygen, to developing new vaccines and serums (chiefly against what we call Hemophilus influenzaea name derived from the fact that it was originally considered the etiological agentand several types of pneumococci). Only one therapeutic measure, transfusing blood from recovered patients to new victims, showed any hint of success."
In 1931, viral growth in embryonated hens' eggs was reported by Ernest William Goodpasture and colleagues at Vanderbilt University. The work was extended to the growth of influenza virus by several workers, including Thomas Francis, Jonas Salk, Wilson Smith, and Macfarlane Burnet, leading to the first experimental influenza vaccines.Plotkin, S.L. and Plotkin, S.A. "A short history of vaccination". In: Vaccines, Stanley A. Plotkin, Walter A. Orenstein, Paul A. Offit, eds. Elsevier Health Sciences, 2008, pp. 6–7. In the 1940s, the US military developed the first approved inactivated vaccines for influenza, which were used during World War II.Artenstein, A. W. "Influenza" In: Vaccines: A Biography, Andrew W. Artenstein, ed. pp. 191–205. Hens' eggs continued to be used to produce virus used in influenza vaccines, but manufacturers made improvements in the purity of the virus by developing improved processes to remove egg proteins and to reduce systemic reactivity of the vaccine. In 2012, the US Food and Drug Administration (FDA) approved influenza vaccines made by growing virus in cell cultures, and influenza vaccines made from recombinant proteins were approved in 2013.
Acceptance The egg-based technology for producing influenza vaccine was created in the 1950s. In the US swine flu scare of 1976, President Gerald Ford was confronted with a potential swine flu pandemic. The vaccination program was rushed, yet plagued by delays and public relations problems. Meanwhile, maximum military containment efforts succeeded unexpectedly in confining the new strain to the single army base where it had originated. On that base, several soldiers fell severely ill, but only one died. The program was canceled after about 24% of the population had received vaccinations. An excess in deaths of 25 over normal annual levels as well as 400 excess hospitalizations, both from Guillain–Barré syndrome, were estimated to have occurred from the vaccination program itself, demonstrating that the vaccine itself is not free of risks. A 2010 study found a significantly enhanced immune response against the 2009 pandemic H1N1 in study participants who had received vaccination against the swine flu in 1976. The 2009 H1N1 swine flu outbreak resulted in the rapid approval of pandemic influenza vaccines. Pandemrix was quickly modified to target the circulating strain and by late 2010, 70 million people had received a dose. Eight years later, the British Medical Journal (BMJ) gained access to early vaccine pharmacovigilance reports compiled by GlaxoSmithKline during the pandemic, which the BMJ reported indicated death was 5.39 times more likely with Pandemrix versus the other pandemic vaccines. However, more thorough and robust later analyses did not establish any increase of fatalities or most other serious adverse effects, with a possible rare exception for narcolepsy.
Quadrivalent vaccines
A quadrivalent flu vaccine administered by nasal mist was approved by the US Food and Drug Administration (FDA) in March 2012. Fluarix Quadrivalent was approved by the FDA in December 2012.
A literature review of quadrivalent influenza vaccines was published in 2014.
Starting with the 2018–2019 influenza season most of the regular-dose egg-based flu shots and all the recombinant and cell-grown flu vaccines in the United States were quadrivalent. In the 2019–2020 influenza season all regular-dose flu shots and all recombinant influenza vaccine in the United States were quadrivalent. However, as of the 2026-2027 flu vaccination year, all US-licensed vaccines returned to exclusively trivalence.
In November 2019, the FDA approved Fluzone High-Dose Quadrivalent for use in the United States starting with the 2020–2021 influenza season.
In February 2020, the FDA approved Fluad Quadrivalent for use in the United States. In July 2020, the FDA approved both Fluad and Fluad Quadrivalent for use in the United States for the 2020–2021 influenza season.
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, and there have been no naturally occurring cases confirmed since March 2020. 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. For the 2024–2025 Northern Hemisphere influenza season, the FDA recommends removing B/Yamagata from all influenza vaccines.
Combination vaccines A combined messenger RNA vaccine for protection against influenza and COVID-19 was introduced in 2026.
Medical uses The influenza vaccine is indicated for active immunization for the prevention of influenza disease caused by influenza virus subtypes A and type B contained in the vaccine. The US Centers for Disease Control and Prevention (CDC) recommends the flu vaccine as the best way to protect people against the flu and prevent its spread. The flu vaccine can also reduce the severity of the flu if a person contracts a strain that the vaccine did not contain. It takes about two weeks following vaccination for protective antibodies to form.
A 2012 meta-analysis found that flu vaccination was effective 67percent of the time; the populations that benefited the most were HIV-positive adults aged 18 to 55 (76percent), healthy adults aged 18 to 46 (approximately 70percent), and healthy children aged six months to 24 months (66percent). The influenza vaccine also appears to protect against myocardial infarction with a benefit of 15–45%.
Effectiveness US vaccine effectiveness by start year: 2004 10% 2005 21% 2006 52% 2007 37% 2008 41% 2009 56% 2010 60% 2011 47% 2012 49% 2013 52% 2014 19% 2015 48% 2016 40% 2017 38% 2018 29% 2019 39% 2020 Unknown 2021 36% 2022 30% 2023 44% 2024 56%
A vaccine is assessed by its efficacy – the extent to which it reduces the risk of disease under controlled conditions – and its effectiveness – the observed reduction in risk after the vaccine is put into use. In the case of influenza, effectiveness is expected to be lower than the efficacy because it is measured using the rates of influenza-like illness, which is not always caused by influenza. Studies on the effectiveness of flu vaccines in the real world are difficult; vaccines may be imperfectly matched, virus prevalence varies widely between years, and influenza is often confused with other influenza-like illnesses. However, in most years (16 of the 19 years before 2007), the flu vaccine strains have been a good match for the circulating strains, and even a mismatched vaccine can often provide cross-protection. The virus rapidly changes due to antigenic drift, a slight mutation in the virus that causes a new strain to arise.
The effectiveness of seasonal flu vaccines varies significantly, with an estimated average efficacy of 40–60% against symptomatic disease, depending on vaccine strain, age, prior immunity, and immune function, so vaccinated people can still contract influenza. The effectiveness of flu vaccines is considered to be suboptimal, particularly among the elderly, but vaccination is still beneficial in reducing the mortality rate and hospitalization rate due to influenza as well as duration of hospitalization. Vaccination of school-age children has shown to provide indirect protection for other age groups. LAIVs are recommended for children based on superior efficacy, especially for children under 6, and greater immunity against non-vaccine strains when compared to inactivated vaccines.
From 2012 to 2015 in New Zealand, vaccine effectiveness against admission to an intensive care unit was 82%. 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. One review found 31% effectiveness against death among adults.
Repeated annual influenza vaccination generally offers consistent year-on-year protection against influenza. There is, however, suggestive evidence that repeated vaccinations may cause a reduction in vaccine effectiveness for certain influenza subtypes, possibly related to immune imprinting, a phenomenon in which the immune system preferentially recalls responses from earlier influenza exposures. , the CDC recommends a yearly vaccine as most studies demonstrate overall effectiveness of annual influenza vaccination.
There is not enough evidence to establish significant differences in the effectiveness of different influenza vaccine types, but there are high-dose or adjuvanted products that induce a stronger immune response in the elderly.
According to a 2016 study by faculty at the University of New South Wales, getting a flu shot was as effective or better at preventing a heart attack than even quitting smoking.
A 2024 CDC study found that the 2024 flu vaccine reduced the risk of hospitalization from the flu by 35% in the Southern Hemisphere. The research, conducted across five countries—Argentina, Brazil, Chile, Paraguay, and Uruguay—showed the vaccine was less effective than the one used in the previous season.
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