Influenza Vaccine

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Continuing Education Activity

Influenza viruses belong to Orthomyxoviridae RNA virus family and classify into three distinct types based on their major antigenic differences; influenza A, influenza B and influenza C. Influenza viruses cause the annual human epidemics, seasonal and pandemic. Seasonal influenza epidemics caused by influenza A and B viruses result in 3 to 5 million severe cases and thousands of deaths globally each year. This activity describes the mode of action of influenza vaccine, including modes of administration, formulations, adverse event profiles, eligible patient populations, monitoring, and highlights the role of the interprofessional team in the management of these patients.


  • Identify the types of influenza viruses requiring vaccinations.
  • Summarize the absolute and relative contraindications of the vaccine.
  • Review the methods of administering influenza vaccination and eligible patients for each type of vaccine.
  • Explain interprofessional team strategies for improving care coordination and communication to advance influenza vaccination and improve patient outcomes.


Influenza viruses belong to Orthomyxoviridae RNA virus family and classify into three distinct types based on their major antigenic differences; influenza A, influenza B and influenza C.  Influenza viruses cause the annual human epidemics, seasonal and pandemic. Seasonal influenza epidemics caused by influenza A and B viruses result in 3–5 million severe cases and thousands of deaths globally each year. Influenza pandemics caused by influenza A virus emerge at unpredictable intervals. The influenza A virus will cause epidemics and pandemics because of its spread from migrating birds, pigs, horses, and humans. Transmission can be human to human from fomites, coughing and sneezing. Pandemics are responsible for increased morbidity and mortality, compared with seasonal influenza. Four such pandemics have occurred in the past century, during 1918, 1957, 1968, and 2009. Influenza B causes only human to human spread with a particular emphasis on the fact that no other hosts are involved, therefore, not involved in pandemics. Influenza C is a mild disease.[1] It causes seasonal episodes of influenza such as Northern infections when they happen from September to March while Southern infections happen from May to September. Due to the variation in viruses responsible for infections in these two seasons; it needs two different sets of vaccines. Influenza generally has an incubation period of 2 days, ranging from 1 to 4 days.  

FDA-approved Indications

  1. Prevention of Influenza A in persons aged 6 months and above
  2. Prevention of Influenza B in persons aged 6 months and above

The Centers for Disease Control and Prevention (CDC) recommends administration of an annual influenza vaccine for all persons above 6 months of age.

The vaccination is the most effective method for prevention and control of influenza. It is most effective in children greater than 2 years old and healthy adults. The efficacy of the seasonal influenza vaccine ranges between 10% and 60%. The lowest efficacy occurs when vaccine strains are not well matched to circulating strains. Both the trivalent and quadrivalent vaccines are FDA approved.[2]

Regarding immunization in pregnancy, a randomized controlled trial conducted in South Africa has shown that when pregnant women receive the influenza vaccine, it halves their risk of developing influenza while reducing the risk of their infants (up to 24 weeks) contracting the illness.[3]

Data shows the trivalent influenza vaccine provides protection in HIV-infected adults without severe immunosuppression while the effectiveness in HIV-infected children aged <5 years is somewhat uncertain. In certain groups, including the elderly, immune-compromised individuals and infants, the influenza vaccine is less effective, but it is beneficial by reducing the incidence of severe disease, like bronchopneumonia, and reduces hospital admission and mortality.[4]

Mechanism of Action

Influenza viruses express two types of antigens; hemagglutinin (HA) and neuraminidase (NA). Influenza A virus has 18 HA, and 11 NA subtypes and these antigens are critical for the virulence of the organism. The trimeric hemagglutinin glycoprotein acts by promoting attachment of the virus to the host cell surface resulting in fusion and thereby releasing virions into the cytoplasm.[1] 

Differently combined H and N antigens are seen in influenza A, that in turn undergo antigenic drifts and shifts resulting in antigenic variation and thereby the necessity for vaccine strain types to vary accordingly. Antigenic drifts are genetic changes occurring in the virus due to various actions of polymerases leading to gradual antigenic changes in both HA and NA producing new variant strains. An antigenic shift takes place when the currently circulating virus disappears and gets replaced by a new subtype with novel glycoproteins to which antibodies against the previously circulating subtype do not cross-react.[5]

Influenza vaccine conveys immunity against the influenza virus by stimulating the production of antibodies specific to the disease. Antibodies to NA act by aggregating viruses on the cell surface effectively and reducing the amount of virus released from infected cells.  Regarding the induction of immunity, the surface HA protein of the influenza virus contains two structural elements, head and stalk wherein the head is the primary target of antibodies that confer protective immunity against influenza viruses.[1]

Flu shots offer protection against three or four strains of the flu virus. Trivalent flu vaccines provide protection against two influenza A strains, H1N1 and H3N2, and one influenza B strain. Quadrivalent flu vaccines protect against the same strains as the trivalent vaccine as well as an additional strain of influenza B.[6]

The mechanism of immune protection is more complicated, as while primarily humoral, cell-mediated immunity also plays an essential role in immunity to influenza. After vaccination, it takes two weeks to build up an immune response against the flu. The effectiveness of a vaccine depends on several host factors such as age, underlying health status, genetic status and furthermore on antigenic matches between the vaccine and circulating viruses.[7]


Flu shots are available in several forms[8][9][10]:

  • Intramuscular vaccine 
  • High-dose vaccine (> 65 years)
  • Intradermal vaccine (18 to 64years)
  • Egg-free vaccine (>4 years)
  • Nasal spray (2 to 49years)
  • Needle-free vaccine as a jet injector (18 to 64 years)


  • Age 6 months to 3 years;

0.25 - 0.5 ml: 2 doses 4 weeks apart.

  • Age 3 to 8 years:

Not previously vaccinated: 2 doses, 0.5 ml 4 weeks apart.

Vaccinated previous season; 0.5 ml one or two doses 4 weeks apart.

  • Age 9 years and above[11]:

Single dose;  0.5 ml

Adverse Effects

  • Injection site reactions
  • Fever
  • Irritability
  • Drowsiness
  • Myalgia
  • Nasal spray 
    • Upper respiratory symptoms
    • Fever, headache, vomiting
    • Lower respiratory symptoms
  • Rare 
    • Allergic reaction
    • Urticaria/Anaphylaxis


  • History of allergy or hypersensitivity to any component of the vaccine (i.e., egg protein allergy)
  • Infants less than 6 months of age
  • High fever
  • Guillain–Barre Syndrome[12]


CDC and FDA continuously monitor vaccine safety and will inform health officials, health care providers, and the public when necessary.

CDC uses three systems vaccine safety monitoring:

  1. The Vaccine Adverse Event Reporting System (VAERS): an early warning system that helps CDC and FDA monitor problems following vaccination.  Anyone can report possible vaccine side effects to VAERS.
  2. The Vaccine Safety Data link (VSD): a collaborative effort between the CDC and nine other health care organizations, which allows ongoing monitoring and proactive searches of vaccine-related data.
  3. The Clinical Immunization Safety Assessment (CISA) Project: a partnership between CDC and several medical centers that conduct clinical research on vaccine-associated health risks.[13]

Inactivated flu vaccine and pneumococcal vaccine administered at the same time may show an increased risk for febrile seizures.


The vaccine does not manifest any dose-dependent toxicity.

The toxicity regarding carcinogenicity and infertility have undergone extensive study and shown to be negative. 

The components of the influenza vaccine are: 

  • Formaldehyde used to inactivate toxins from viruses and bacteria. 
  • Thimerosal safeguards against contamination, and it is only present in multi-dose vials.
  • Aluminum salts act as adjuvants and impart stronger immune response.
  • Gelatin is present as a stabilizer. 
  • Antibiotics, such as gentamicin or neomycin are present in the flu vaccine to keep bacteria from growing.

Toxicity due to the components of the vaccine is not present due to the inconspicuous amounts in the vaccine.[14][15]

Enhancing Healthcare Team Outcomes

Vaccination is the primary strategy for prevention and control of influenza. The success of the vaccination depends upon the promotion by the health workers, like physicians, nurses, pharmacists, and other health care professionals. A proper understanding of the vaccine benefits is mandatory. Discouraging the vaccination for trivial reasons should be avoided.

Encourage health professionals at risk to vaccinate themselves.

Pregnant women should be protected either by individual vaccination or by cocoon protection by vaccinating the surrounding people. Vaccinating the pregnant women is preferable. Influenza infection after vaccination tends to less severe, and complications also reduced. And it helps to protect the baby against flu during the crucial first six months of life as the mother passes the immune protection to her newborn.[16][3]

The real challenge in the primary strategy for prevention and control of the influenza virus is the antigenic drifts and shifts. Annual vaccination is the current recommendation due to waning immunity.

A Universal influenza vaccine is undergoing trials and serves the purpose of building a single vaccine which targets all strains of the virus; this will, in turn, minimize the need for frequent vaccination and be the bright future of this vaccination.[17][18]

Article Details

Article Author

Saieda Kalarikkal

Article Editor:

Gayatri Jaishankar


2/16/2021 7:40:29 PM

PubMed Link:

Influenza Vaccine



Kirkpatrick E,Qiu X,Wilson PC,Bahl J,Krammer F, The influenza virus hemagglutinin head evolves faster than the stalk domain. Scientific reports. 2018 Jul 11;     [PubMed PMID: 29992986]


Grohskopf LA,Sokolow LZ,Broder KR,Walter EB,Fry AM,Jernigan DB, Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices-United States, 2018-19 Influenza Season. MMWR. Recommendations and reports : Morbidity and mortality weekly report. Recommendations and reports. 2018 Aug 24;     [PubMed PMID: 30141464]


Giles ML,Krishnaswamy S,Wallace EM, Maternal immunisation: What have been the gains? Where are the gaps? What does the future hold? F1000Research. 2018;     [PubMed PMID: 30443339]


Cohen C,Tshangela A,Valley-Omar Z,Iyengar P,von Mollendorf C,Walaza S,Hellferscee O,Venter M,Martinson N,Mahlase G,McMorrow M,Cowling BJ,Treurnicht FK,Cohen AL,Tempia S, Household transmission of seasonal influenza from HIV-infected and -uninfected individuals in South Africa, 2013-2014. The Journal of infectious diseases. 2018 Dec 12;     [PubMed PMID: 30541140]


Franco-Paredes C,Carrasco P,Preciado JI, The first influenza pandemic in the new millennium: lessons learned hitherto for current control efforts and overall pandemic preparedness. Journal of immune based therapies and vaccines. 2009 Aug 7;     [PubMed PMID: 19664217]


Rudenko L,Kiseleva I,Krutikova E,Stepanova E,Rekstin A,Donina S,Pisareva M,Grigorieva E,Kryshen K,Muzhikyan A,Makarova M,Sparrow EG,Torelli G,Kieny MP, Rationale for vaccination with trivalent or quadrivalent live attenuated influenza vaccines: Protective vaccine efficacy in the ferret model. PloS one. 2018;     [PubMed PMID: 30507951]


Lim JW,Na W,Kim HO,Yeom M,Park G,Kang A,Chun H,Park C,Oh S,Le VP,Jeong HH,Song D,Haam S, Cationic Poly(Amino Acid) Vaccine Adjuvant for Promoting Both Cell-Mediated and Humoral Immunity Against Influenza Virus. Advanced healthcare materials. 2018 Dec 14;     [PubMed PMID: 30549426]


Sano K,Ainai A,Suzuki T,Hasegawa H, Intranasal inactivated influenza vaccines for the prevention of seasonal influenza epidemics. Expert review of vaccines. 2018 Aug;     [PubMed PMID: 30092690]


McAllister L,Anderson J,Werth K,Cho I,Copeland K,Le Cam Bouveret N,Plant D,Mendelman PM,Cobb DK, Needle-free jet injection for administration of influenza vaccine: a randomised non-inferiority trial. Lancet (London, England). 2014 Aug 23;     [PubMed PMID: 24881803]


Choi IJ,Kang A,Ahn MH,Jun H,Baek SK,Park JH,Na W,Choi SO, Insertion-responsive microneedles for rapid intradermal delivery of canine influenza vaccine. Journal of controlled release : official journal of the Controlled Release Society. 2018 Sep 28;     [PubMed PMID: 30102940]


Belshe RB,Edwards KM,Vesikari T,Black SV,Walker RE,Hultquist M,Kemble G,Connor EM, Live attenuated versus inactivated influenza vaccine in infants and young children. The New England journal of medicine. 2007 Feb 15;     [PubMed PMID: 17301299]


Klimek L,Wicht-Langhammer S,von Bernus L,Thorn C,Cazan D,Pfaar O,Hörmann K, [Anaphylactic reactions to vaccines : Chicken egg allergy and the influenza H1N1 vaccination]. HNO. 2017 Oct;     [PubMed PMID: 28540396]


Baggs J,Gee J,Lewis E,Fowler G,Benson P,Lieu T,Naleway A,Klein NP,Baxter R,Belongia E,Glanz J,Hambidge SJ,Jacobsen SJ,Jackson L,Nordin J,Weintraub E, The Vaccine Safety Datalink: a model for monitoring immunization safety. Pediatrics. 2011 May;     [PubMed PMID: 21502240]


Sasaki E,Momose H,Hiradate Y,Mizukami T,Hamaguchi I, Establishment of a novel safety assessment method for vaccine adjuvant development. Vaccine. 2018 Nov 12;     [PubMed PMID: 30318166]


Del Giudice G,Rappuoli R,Didierlaurent AM, Correlates of adjuvanticity: A review on adjuvants in licensed vaccines. Seminars in immunology. 2018 Oct;     [PubMed PMID: 29801750]


Stead M,Critchlow N,Patel R,MacKintosh AM,Sullivan F, Improving uptake of seasonal influenza vaccination by healthcare workers: Implementation differences between higher and lower uptake NHS trusts in England. Infection, disease     [PubMed PMID: 30541694]


Elbahesh H,Saletti G,Gerlach T,Rimmelzwaan GF, Broadly protective influenza vaccines: design and production platforms. Current opinion in virology. 2018 Nov 26;     [PubMed PMID: 30497050]


Bresee JS,McKinlay MA,Abramson J,Klugman KP,Wairagkar N, Global Funders Consortium for Universal Influenza Vaccine Development. Vaccine. 2018 Nov 29;     [PubMed PMID: 30503660]