How is the flu vaccine made?
Every year in January or February, public health officials travel abroad to determine the composition of circulating influenza viruses, assuming that those same viruses will arrive in the United States or the rest of the world several months later, in October or November. (at the beginning of flu season), making many people sick. Then, as it is determined in advance which flu viruses will be circulating later that year, vaccine manufacturers are instructed to include those particular strains in their products.
For example, during the 2016-2017 flu season vaccines were required to contain:(1)
- A/California/7/2009(HlNl);
- A/HongKong/4801/2014(H3N2);
- B/Brisbane/60/2008.
During the 2007-2008 flu season, vaccines contained completely different strains:(2)
- A/Solomonlslands/3/2006(H1N1);
- A/Wisconsin/67/2005(H3N2);
- B/Malaysia/2506/2004
Since influenza is caused by several influenza viruses, they have been classified into types A, B, and C, then further classified into subtypes named after cities, states, or countries).
The influenza strains used to produce the vaccines are also chosen for "properties that make them easily cultivable on eggs".(3) This is crucial because viruses need to be inoculated into chicken embryos for production. This mixture is left in culture for several weeks, then each strain is inactivated with formaldehyde(4) and preserved with a mercury salt called thimerosal.(5) Mercury is a neurotoxic metal and, despite being removed from numerous pediatric vaccines, many flu vaccines still contain 25 μg per dose.(6-7-8) Flu medicines may also contain polyethylene glycol, polysorbate 80, hydrocortisone, neomycin and polymyxin (antibiotics), sodium deoxycholate, MSG and porcine (pork) gelatin.(9)
The 3 viral strains are mixed into a single vaccine, authorized and then distributed.
No control groups are required to scientifically test the effectiveness and safety of the drug.(10)
NOTE: Below you will find the commonly used vaccines, but not all of them are necessarily approved for the current season. Check the approval determination for the current year on the AIFA website.
Fluad Tetra - Seqirus Netherlands (click to open)
Influenza vaccine (surface antigen, inactivated, adjuvanted)
Dosage declared by the manufacturer
The use of Fluad Tetra is not indicated in children.
Adverse events declared by the manufacturer
- Injection site pain
- Fatigue
- Headache
- Joint pain (arthralgia)
- Muscle pain (myalgia)
- Redness at the injection site (erythema)
- Hardening of the skin at the injection site
- Diarrhea
- Chills
- Nausea
- Loss of appetite
- Bruising at the injection site (ecchymosis)
- Sintomi simil influenza
- Threw up
- Fever (≥ 38 °C)
In addition to the side effects described above, the following side effects have occasionally occurred during general use of Fluad Tetra or a similar vaccine:
- reduction in the number of certain blood particles called platelets; a low number of platelets can increase bruising or bleeding (thrombocytopenia)
- swelling of the glands in the neck, armpits or groin (lymphadenopathy)
- swelling, pain and redness at the injection site (cellulitis-like reaction at the injection site)
- extensive swelling of the limb where the injection was given lasting more than a week
- general weakness or lack of energy (asthenia), general feeling of being unwell (malaise)
- fever (pyrexia)
- muscle weakness
- pain along the course of a nerve (neuralgia), abnormalities in the perception of touch, pain, heat and cold (paraesthesia), seizures, neurological disorders which may cause stiffness in the back of the neck, confusion, numbness, pain and weakness in the limbs, loss of balance, loss of reflexes, paralysis of parts of the body or the whole body (encephalomyelitis, neuritis, Guillain-Barré syndrome)
- skin reactions which may spread over the whole body including feeling itchy skin (pruritus, urticaria), redness of the skin (erythema), non-specific skin rash, severe skin rash (erythema multiforme),
- swelling more evident in the head and neck, including the face, lips, tongue, throat, or any other part of the body (angioedema
- swelling of blood vessels which can cause skin rashes (vasculitis) and temporary kidney problems
- fainting, feeling of fainting (syncope, presyncope)
Composition declared by the manufacturer
- A/Victoria/4897/2022 (H1N1)pdm09‐ceppo
- A/Darwin/9/2021 (H3N2)-strain equivalent
- B/Austria/1359417/2021-equivalent strain
- B/Phuket/3073/2013-equivalent strain
- Adjuvant MF59C.1
- squalene
- polysorbate 80
- sorbitan trioleate
- sodium citrate
- citric acid
Fluad Tetra may contain traces of egg, such as ovalbumin or chicken protein, kanamycin and neomycin sulfate, formaldehyde, hydrocortisone, cetyltrimethylammonium bromide (CTAB), which are used during the manufacturing process.
Fluenz Tetra nasal spray - AstraZeneca (click to open)
Fluenz Tetra Nasal Spray, Suspension Influenza Vaccine (Live Attenuated, Nasal)
It is a vaccine that prevents flu. It is used in children and adolescents aged between 24 months and 18 years. The viruses contained in the Fluenz Tetra vaccine were grown on chicken eggs. Each year the vaccine is directed against four strains of influenza viruses, based on annual recommendations from the World Health Organization.
Dosage declared by the manufacturer
Children who have not previously been vaccinated against seasonal influenza should be given a second dose at least 4 weeks apart from the first.
It should not be used in infants and children younger than 24 months due to safety concerns regarding increased rates of hospitalization and dyspnea in this population
Immunization must occur by nasal administration
Adverse events declared by the manufacturer
- Hypersensitivity reactions (including facial edema, urticaria and, very rarely, anaphylactic reactions)
- Decreased appetite
- Migraine
- Nasal congestion/rhinorrhea
- Epistaxis
- Rash
- Myalgia
- Sense of malaise
- Pyrexia
- Guillain-Barré syndrome
- worsening of Leigh syndrome (mitochondrial encephalomyopathy)
- In an active-controlled clinical trial (MI-CP111), an increased rate of hospital admissions (from any cause) was observed within 180 days following final vaccination in infants and children aged 6 to 11 months (6,1 .2,6% with trivalent Fluenz compared to 6% with the injectable influenza vaccine). Most hospitalizations were due to gastrointestinal and respiratory tract infections and occurred more than 12 weeks after vaccination. The rate of hospitalization did not increase in subjects older than 42 months who took trivalent Fluenz. In the same study, an increased rate of wheezing over 6 days was observed in infants and children aged 23 to 5,9 months (3,8% with trivalent Fluenz versus 24% with injectable influenza vaccine). The rate of dyspnea did not increase in subjects older than 24 months who took trivalent Fluenz. Fluenz Tetra is not indicated in infants and children under XNUMX months of age
Composition declared by the manufacturer
Recombinant influenza virus (propagated in fertilized chicken eggs from healthy flocks) of the following four strains produced in VERO cells by reverse genetic engineering. The product contains genetically modified organisms (GMOs):
- A/Strain similar to strain Victoria/4897/2022 (H1N1)pdm09 (A/Norway/31694/2022, MEDI 369815)
- A/Strain similar to Darwin/9/2021 (H3N2) strain (A/Norway/16606/2021, MEDI 355293) ***
- B/Strain similar to strain Austria/1359417/2021 (B/Austria/1359417/2021, MEDI 355292)***
- B/Strain similar to Phuket/3073/2013 strain (B/Phuket/3073/2013, MEDI 306444)
- Egg proteins (e.g. ovalbumin)
- Gentamicin
- Sucrose
- Dipotassium phosphate Potassium dihydrogen phosphate
- Gelatin (porcine, type A)
- Arginine hydrochloride
- Monosodium glutamate monohydrate
- Water for injections
Flucelvax Tetra - Seqirus Netherlands BV (click to open)
Influenza vaccine (surface antigen, inactivated, produced in cell culture)
Dosage declared by the manufacturer
Influenza prophylaxis in adults and children from the age of 2 years.
The safety and effectiveness of Flucelvax Tetra in children from birth to less than 2 years of age have not been established.
Adverse events declared by the manufacturer
- Injection site pain, bruising, redness and hardness or swelling at the injection site.
- Headache
- Muscular pain
- Fatigue
- Loss of appetite
- Irritability (reported only in children aged 2 to < 6 years)
- Drowsiness (reported only in children aged 2 to < 6 years)
- Hardness or swelling at the injection site, headache, muscle pain, and tiredness were common in older adults.
- Injection site bruising was common in adults, older adults, and children aged 9 to <18 years.
- Headaches were common in the elderly.
- Loss of appetite was common in adults, older adults, and children aged 9 to <18 years.
- Nausea, vomiting, diarrhea
- Joint pain
- Chills
- Change in eating habits (reported only in children aged 2 to < 6 years)
- Fever (> 38°C)
- Feeling of numbness and tingling (paraesthesia)
- Generalized skin reactions, including itching, skin bumps (pruritus, hives), or nonspecific rash
Composition declared by the manufacturer
- A/Wisconsin/67/2022 (H1N1))pdm09-strain equivalent (A/Georgia/12/2022 CVR-167)
- A/Darwin/6/2021 (H3N2)-strain equivalent (A/Darwin/11/2021, wild type)
- B/Austria/1359417/2021-strain equivalent (B/Singapore/WUH4618/2021, wild type)
- B/Phuket/3073/2013-strain equivalent (B/Singapore/INFTT-16-0610/2016, wild type)
- beta-propiolactone
- cetyltrimethylammonium bromide
- polysorbate 80
- Sodium chloride
- Potassium chloride
- Magnesium chloride hexahydrate
- Disodium phosphate dihydrate
- Potassium dihydrogen phosphate
- Water for injections
Vaxigrip Tetra - Sanofi (click to open)
Quadrivalent influenza vaccine (prepared with inactivated "split" fragmented viruses), suspension for injection in pre-filled syringe.
This vaccine is given to adults and children from 6 months of age
The vaccine will not protect against the common cold, even if some of the symptoms are similar to those of the flu.
Dosage declared by the manufacturer
For adults, annual revaccination is recommended.
Children from 6 months to 17 years of age: one dose. Children under 9 years of age who have not previously been vaccinated should be given a second dose after an interval of at least 4 weeks.
Adverse events declared by the manufacturer
- Lymphadenopathy
- Hypersensitivity
- allergic reactions such as angioedema, allergic dermatitis, generalized pruritus, urticaria, pruritus, erythema
- Headache
- Dizziness
- Paraesthesia
- Drowsiness
- Hot flashes
- Dyspnoea
- Diarrhoea, nausea
- Hyperhidrosis
- Myalgia
- Arthralgia
- Malaise
- Pain at the injection site
- Chills, fever
- Injection site erythema,
- Swelling at the injection site, induration at the injection site
- Fatigue,
- Bruising at the injection site,
- Itching at the injection site, warmth at the injection site
- Asthenia
- flu-like syndrome
- Discomfort at the injection site
- Thrombocytopenia
- Transient thrombocytopenia
- Allergy including anaphylactic reactions
- Unusual crying, irritability
- Vomit,
- Upper abdominal pain
- Hypersensitivity
- Allergic reactions such as generalized itching
- papular rash
- Anaphylactic reactions
- Loss of appetite
- Influenza-like illness
- Guillain-Barré Syndrome (GBS),
- neurites
- neuralgia
- convulsions
- encephalomyelitis
- Vasculitis, such as Henoch-Schönlein purpura, with transient renal involvement in some cases
Composition declared by the manufacturer
- Influenza viruses (inactivated “splits”) cultured in fertilized eggs of hens from healthy chicken flocks of the following strains:
- A/Victoria/4897/2022 (H1N1)pdm09–equivalent strain (A/Victoria/4897/2022, IVR-238) (hemagglutinin)
- A/Darwin/9/2021 (H3N2)-strain equivalent (A/Darwin/9/20211, IVR-228) (hemagglutinin)
- B/Austria/1359417/2021–equivalent strain (B/Michigan/01/2021, wild type) (hemagglutinin)
- B/Phuket/3073/2013–equivalent strain (B/Phuket/3073/2013, wild type) (hemagglutinin)
- ovalbumin
- neomycin
- formaldehyde
- 9-octoxinol
- sodium chloride
- potassium chloride
- sodium phosphate
- dibasic dihydrate
- potassium dihydrogen phosphate
- water for injections
Influvac S Tetra - Mylan (click to open)
Influenza vaccine (surface antigen, inactivated) in suspension for injection in pre-filled syringes
especially in individuals who have a greater risk of associated complications. It is indicated in adults and children over 6 months of age
Dosage declared by the manufacturer
Dosage Adults: one dose
Pediatric population Children from 36 months onwards: one dose
Children aged 6 months to 35 months: Clinical data are limited.
For children who have not previously been vaccinated, a second dose should be administered after an interval of at least 4 weeks.
Adverse events declared by the manufacturer
- Headache
- Sweating
- Myalgia, arthralgia
- Fever,
- Malaise
- Chills
- Fatigue
- Local reactions: redness, swelling, pain, bruising, induration
- Transient thrombocytopenia
- Transient lymphadenopathy
- Allergic reactions, which in rare cases have led to shock, angioedema
- Neuralgia, paraesthesia
- Febrile seizures
- Neurological disorders such as encephalomyelitis, neuritis and Guillain Barrè syndrome
- Vasculitis associated in very rare cases with transient renal involvement
- Generalized skin reactions including pruritus, urticaria, or nonspecific rash
Composition declared by the manufacturer
- Surface antigens (hemagglutinin and neuraminidase) of the influenza virus, of the following strains, propagated in fertilized chicken eggs from healthy chicken flocks:
- A/Brisbane/02/2018 (H1N1)pdm09-strain equivalent (A/Brisbane/02/2018, IVR-190) (hemagglutinin)
- A/Kansas/14/2017 (H3N2)-strain equivalent (A/Kansas/14/2017, NYMC X-327) (hemagglutinin)
- B/Colorado/06/2017-strain equivalent (B/Victoria/2/87 lineage) (B/Maryland/15/2016, NYMC BX-69A) (hemagglutinin)
- Ovalbumin
- Chicken protein
- formaldehyde
- Cetyltrimethyllammonium bromide
- polysorbate 80 or gentamicin
References (click to open)
- WHO, "Recommended composition of influenza virus vaccines for use in the 2016-2017 northern hemisphere influenza season", www.who.int.
- CDC, “Prevention and control of influenza: recommendations of the ACIP, 2007,” MMWR, July 13, 2007; 56 (RR06), pp. 1-54. See also: CDC, "2007-08 influenza prevention & control recommendations for using TIV and LAIV during the 2007-08 influenza season", www.cdc.gov, 26 October 2007.
- Ibid.
- Sanofi Pasteur, Inc. - Fluzone®; GSK - Fluarix®; ID Biomedical Corp. -FluLaval®. Influenza virus vaccine 2008- 2009 formulas. Manufacturers' information leaflets.
- CSL, Ltd.-Afluria®; Sanofi Pasteur, Inc. - Fluzone®; ID Biomedical Corp. - FluLaval®; Novartis-Fluvirin®. Influenza virus vaccine 2008-2009 formulas. Information leaflets.
- Ibid.
- Institute for Vaccine Safety, “Thimerosal content in some US licensed vaccines,” Johns Hopkins Bloomberg School of Public Health, August 6, 2008, www.vaccinesafety.edu/thi-table.htm
- FDA, “Thimerosal in vaccines: Table 3,” updated September 6, 2007, www.fda.gov/CBER/vaccine/thimerosal.htm
- See Note 13. See also: ID Biomedical-Fluarix; Medlmmune - FluMist®. Influenza virus vaccine 2008-2009 formulas. Information leaflets.
- Connaught Laboratories, “The making of a flu vaccine,” LA Times, reprinted Kansas City Star, February 24, 1993.
