Influenza vaccination

Influenza is a major cause of morbidity and mortality each year in the UK. Vaccination has been available since the late 1960s. It is offered annually to patients aged over 65 years, and to all those aged between 6 months and 65 years in clinical at-risk groups identified by the Department of Health.

All but one of the influenza vaccines available in the UK are inactivated and do not contain live viruses. Inactivated vaccines are usually administered intramuscularly. Inactivated influenza vaccines contain two subtypes of influenza A and two subtypes of influenza B virus. Fluenz® Tetra is a quadrivalent attenuated live vaccine administered by nasal spray.¹

Influenza vaccines²

The use of quadrivalent influenza vaccines containing a B strain from each lineage is expected to improve the match of the vaccine and therefore offer wider protection against circulating influenza B viruses.

Because influenza B is relatively more common in children, the vaccines centrally purchased for the childhood programme in recent years have been quadrivalent preparations. The childhood programme will contribute to better control of influenza B overall by reducing transmission across the population.

Surveillance is ongoing for the B/Yamagata lineage following marked reduction in detections due to non-pharmaceutical interventions against COVID-19 throughout 2020 to 2022.

Demonstration of extinction of the B/Yamagata lineage would be indication for a return to trivalent influenza vaccines. The influenza vaccines marketed in the UK for the 2023 to 2024 season are:

• Fluenz® Tetra: quadrivalent LAIV (live attenuated influenza vaccine) supplied as nasal spray suspension. For individuals from 24 months to less than 18 years of age.

• Quadrivalent influenza vaccine: QIVe (standard egg-grown quadrivalent influenza vaccine), split virion, inactivated. For individuals from 6 months of age.

• Influvac® sub-unit Tetra: QIVe (standard egg-grown quadrivalent influenza vaccine), surface antigen, inactivated. For individuals from 6 months of age.

• Cell-based quadrivalent influenza vaccine Seqirus: QIVc (cell-grown quadrivalent influenza vaccine), surface antigen, inactivated. For individuals from 2 years of age.

• Supemtek: QIVr; quadrivalent influenza vaccine (recombinant, prepared in cell culture). For individuals from 18 years of age.

• Adjuvanted quadrivalent influenza vaccine Seqirus: aQIV (adjuvanted egg-grown quadrivalent influenza vaccine) surface antigen, inactivated, adjuvanted with MF59C.1. For individuals from 65 years of age.

The following vaccines carry a black triangle symbol (the Commission on Human Medicines and the Medicines and Healthcare products Regulatory Agency encourage the reporting of all suspected reactions to newer drugs and vaccines, which are denoted by an inverted Black Triangle symbol ▼):

• Adjuvanted quadrivalent inactivated influenza vaccine (aQIV, made by Seqirus).

• Quadrivalent cell-cultured inactivated influenza vaccine (QIVc made by Seqirus).

• Recombinant quadrivalent inactivated influenza vaccine (QIVr, Supemtek, made by Sanofi Pasteur) and Quadrivalent Influvac® sub-unit Tetra, an inactivated egg-based influenza vaccine (a QIVe made by Viatris, formerly Mylan).

• High-dose quadrivalent inactivated influenza vaccine (QIV-HD).

The LAIV is thought to provide broader protection than inactivated vaccines, and therefore has potential to offer better protection against strains that have undergone antigenic drift compared to the original virus strains in the vaccine. LAIV has been shown to provide a higher level of protection for children than trivalent inactivated influenza vaccine.

The Joint Committee on Vaccination and Immunisation (JCVI) has advised (September 2021) that in those aged 65 years and over, a quadrivalent formulation of the adjuvanted vaccine (aQIV), recombinant quadrivalent influenza vaccine (QIVr) and QIV-HD are the preferred vaccines and if these are not available then the quadrivalent cell-cultured inactivated vaccine (QIVc) is considered an acceptable alternative.

JCVI has advised the use of QIVr and QIVc for vaccination of adults aged 18 to less than 65 years in an at-risk group. QIVe can also be considered for use in this age group if other options are not available.

The JCVI has advised that for children aged 2 to less than 18 years in an at-risk group for whom LAIV is not suitable, QIVc is the preferred choice followed by QIVe.

For adults aged 50 to 64 years not in a clinical risk group who are offered NHS influenza vaccination, JCVI has advised QIVe is suitable if this supports prioritising more vulnerable cohorts for vaccines considered most effective (JCVI December 2021).

Children:

• 6 months to less than 2 years old: offer suitable quadrivalent inactivated flu vaccine. Those who have not received flu vaccine before should be offered two doses (given at least four weeks apart).

• 2 years to less than 9 years old:

  • Children in clinical risk groups and children who are household contacts of immunocompromised individuals: offer LAIV (unless medically contra-indicated). Those who have not received flu vaccine before should be offered two doses (given at least four weeks apart).

  • Children not in clinical risk groups: offer LAIV.

• Children 9 years to less than 18 years old:

  • Children in clinical risk groups and children who are household contacts of immunocompromised individuals: offer LAIV (unless medically contra-indicated).

  • Children not in clinical risk groups: offer LAIV.

• If LAIV is medically contra-indicated or otherwise unsuitable, then offer quadrivalent inactivated flu vaccine.

Recommendations for use (2023/24)^{1 3}

The following groups of people in England are eligible for a flu vaccine from 1 September 2023 as part of the NHS flu immunization programme:

• Everyone aged 65 years and over.

• Everyone aged 6 months to under 65 years who has a medical condition listed below.

• All pregnant women, at any stage of pregnancy, and including those who become pregnant during the influenza season.

• All children aged 2 and 3 years (provided they were aged 2 or 3 years on 31 August before flu vaccinations starts in the autumn).

• All children in primary school.

• Secondary school-aged children in years 7 to 11.

• Everyone living in a residential or nursing home.

• People in receipt of a carer's allowance, or those who are the main carer of an elderly or disabled person.

• Close contacts of immunocompromised people.

• All frontline social care staff without an employer-led occupational scheme.

Influenza vaccination should ideally be completed by the end of November but can also take place up until the following 31 March.

Adults with a body mass index of 40 kg/m² or above are also eligible, but many of this group will already be eligible due to complications of obesity that place them in another risk category.

Chapter 19 of the 'Green Book' provides the relevant contact details for Scotland, Wales and Northern Ireland.²

The target groups for a one-off pneumococcal vaccination are very similar (see the separate Pneumococcal Vaccination article), so often both are given together in 'flu clinics'.

GPs should take into account the risk of influenza infection exacerbating any underlying disease that a patient may have, as well as the risk of serious illness from influenza itself. GPs should consider on an individual basis the clinical needs of their patients, including individuals with:

• Multiple sclerosis and related conditions.

• Hereditary and degenerative diseases of the central nervous system.

NB: individuals working closely with poultry are no longer thought to be high-risk.

Employers - eg, healthcare trusts and nursing and care homes - should offer influenza vaccination to staff directly involved in patient care as an adjunct to good infection control procedures:

• Clinicians, midwives and nurses, paramedics and ambulance drivers.

• Occupational therapists, physiotherapists and radiographers.

• Primary care providers such as GPs, practice nurses and district nurses.

• Staff who look after older people in nursing and care homes.

Method of administration²

In all settings providing vaccination, facilities should be available and staff trained to recognise and treat anaphylaxis.

• Vaccines are normally given intramuscularly into the upper arm or anterolateral thigh.

• The live attenuated influenza vaccine (LAIV), Fluenz® Tetra, is a nasal spray used for children aged 2-18 years.

• If patients have a bleeding disorder (eg, haemophilia), deep subcutaneous injection is appropriate.

• Influenza vaccine can be given with other vaccines, preferably in different limbs. If both vaccines have to be given in the same limb, the sites should be at least 2.5 cm apart.

• The batch numbers and sites of the vaccines should be recorded in the patient's notes.

• If the vaccine is given for employment purposes, the employer should also keep a record.

Vaccine uptake⁴

Between 1 September 2022 and 28 February 2023, uptake for GP patients in England for influenza vaccinations was:

• 65 years and over: 79.9%.

• 6 months to under 65 years at-risk: 49.1%.

• Pregnant women: 35%.

• 50 to under 65 and not in a clinical risk group: 40.6%.

• 50 to 65 years and in a clinical risk group: 62.4%.

• All 2-year-olds: 42.3%.

• All 3-year-olds: 45.1%.

Efficacy²

The effectiveness of influenza vaccine depends upon the composition of the vaccine, the circulating strains, the type of vaccine and the age of the individual being vaccinated.

• The LAIV is thought to provide broader protection than inactivated vaccines, and therefore has potential to offer better protection against strains that have undergone antigenic drift compared to the original virus strains in the vaccine.

• LAIV has been shown to provide a higher level of protection for children than trivalent inactivated influenza vaccine. A meta-analysis suggested an efficacy against confirmed disease of 83%.

• The use of quadrivalent influenza vaccines containing a B strain from each lineage is expected to improve the match of the vaccine and therefore offer wider protection against circulating influenza B viruses. Influenza B is relatively more common in children.

• Immune responses to vaccination decline substantially with age.

Storage, presentation and disposal²

• Influenza vaccines should be stored in their original packaging at +2°C to +8°C and protected from light.

• LAIV may be left out of the refrigerator/removed from the cold chain for a maximum period of 12 hours at a temperature not above 25°C. If the vaccine has not been used after this 12-hour period, it should be disposed of.

• Extremes of temperature can reduce potency. Freezing can cause hairline cracks in the container.

• All vaccines are supplied in the inactive form in pre-filled syringes (or a nasal applicator) which should be shaken before use.

• Dispose of the vaccination equipment in a sealable, puncture-proof sharps box (UN-approved BN7390).

Dosage and schedule²

Immunocompetent adults, including pregnant women, should be given a single dose of vaccine.

Children

• Two doses of inactivated influenza vaccine may be required to achieve adequate antibody levels in younger children who have not received influenza vaccine before. LAIV has been shown to provide greater protection for children than inactivated influenza vaccine.

• It is important that preterm infants who have risk factors have their immunisations at the appropriate chronological age. Influenza immunisation should be considered after the child has reached 6 months of age.

• Children aged 2 to less than 17 years NOT IN clinical risk groups: a single dose of LAIV should be offered per season, unless contra-indicated, irrespective of whether influenza vaccine has been received previously.

• Children aged 6 months to less than 18 years who are household contacts of immunocompromised individuals: inactivated vaccine may need to be given instead of LAIV.

• Children aged 6 months to less than 2 years IN clinical risk groups: should be offered the recommended inactivated quadrivalent influenza vaccine. Those who have not received influenza vaccine previously should be offered a second dose of vaccine, at least four weeks later.

• Children aged 2 to less than 18 years IN clinical risk groups: should be offered LAIV unless it is medically contra-indicated or otherwise unsuitable. Those children who have never received influenza vaccine before and are aged between 2 and less than 9 years should be offered a second dose of LAIV at least four weeks later. If LAIV is unavailable for this second dose, an inactivated influenza vaccine can be given.

• For those children in clinical risk groups for whom LAIV is medically contra-indicated, a suitable quadrivalent inactivated influenza vaccine should be offered. Children aged 2 to less than 9 years who have not received influenza vaccine previously should be offered a second dose of the vaccine at least four weeks later.

Vaccinated children should avoid contact with severely immunocompromised individuals for two weeks after vaccination.

Immunocompromised patients

Immunocompromised patients (including HIV infection, regardless of CD4 count) should be given influenza vaccine in accordance with the recommendations below. They may not make a full antibody response, so protection may not be as high as for immunocompetent patients.

Consideration should also be given to vaccinating household contacts of immunocompromised patients, ie those sharing living accommodation on most days over the winter.

Contra-indications to all influenza vaccinations²

There are few contra-indications. When in doubt, seek the guidance of a local communicable disease consultant, paediatrician or immunisation co-ordinator. Vaccine should not be given to patients with:

• A confirmed anaphylactic reaction to a previous dose of the vaccine.

• A confirmed anaphylactic reaction to any component of the vaccine.

LAIV should not be given to children or adolescents who are clinically severely immunocompromised due to conditions or immunosuppressive therapy - eg, acute and chronic leukaemias, lymphoma, cellular immune deficiencies, HIV infection not suppressed by antiretroviral therapy, or high-dose oral corticosteroids.

It is not contra-indicated for children or adolescents living with HIV who are receiving antiretroviral therapy and attaining viral suppression. It is contra-indicated in children and adolescents receiving salicylate therapy (other than for topical treatment of localised conditions) because of the association of Reye’s syndrome with salicylates and wild-type influenza infection.

A careful history should rule out previous non-life-threatening reactions (eg, rash, or reactions which were not truly anaphylactic). Seek the advice of a specialist when in doubt.

In addition, live attenuated vaccines are contra-indicated for those who:

• Are clinically severely immunodeficient secondary to a condition or immunosuppressive therapy - eg, leukaemias, HIV (not on active antiretroviral therapy - ART) and high-dose corticosteroids.

• Are receiving salicylate therapy.

• Are severely asthmatic (level 4 or above) or actively wheezing at the time of vaccination.

Precautions²

• Intercurrent illness - vaccination may be postponed in the event of an acute illness, but minor illness without pyrexia or systemic upset should not be a reason for delay.

• Premature infants - at-risk premature infants should have vaccination at the appropriate chronological age.

• HIV infection - immunosuppressed patients should be given the vaccine, irrespective of CD4 count. A full antibody response may not be produced. See above also for Fluenz® Tetra.

Side-effects of influenza vaccine²

NB: side-effects may be more pronounced if both seasonal influenza and swine influenza vaccinations are co-administered.

• Angio-oedema, urticaria, bronchospasm and anaphylaxis can occur. This is an immediate reaction, usually due to hypersensitivity to residual egg protein.

• Neuralgia, paraesthesiae, convulsions and transient thrombocytopenia have been reported rarely.

• Guillain-Barré syndrome has (very rarely) been reported (1-2 cases per million vaccinated people).⁵

• Encephalomyelitis, neuritis (mainly optic) and vasculitis have also (very rarely) been reported but a definite causal relationship with influenza vaccine has not been established.

• All suspected reactions in children and severe suspected reactions in adults should be reported using the Yellow Card Scheme to the Commission on Human Medicines.⁶