The 2018/19 influenza vaccination season is witnessing some major changes with regards to the choice of vaccine.

In previous years some Clinical Commissioning Groups (CCGs) were putting pressure on GP practices to purchase the cheapest influenza vaccine available. There were even cases where practices had to cancel orders for the quadrivalent inactivated vaccine (QIV) for the 2017/18 (last) season, changing their orders for the cheaper trivalent inactivated vaccine (TIV).

Vaccinating children has achieved a statistically significant improvement in the children visiting their GP practices with influenza-like illness.1 A welcome parallel achievement was the statistically significant decrease of adults aged 18 years and over (young adults, elderly, healthy or with chronic disease) visiting their GP practices with influenza-like illness.1,2

Still, the burden of disease and effect on NHS hospitals, social services and primary care has been considerable.

The underlying issue was the low effectiveness3 of the egg-based inactivated influenza vaccines in preventing influenza A(H3N2) disease, the dominant A virus circulating, as well as the dominant influenza B/Yamagata lineage that was in QIV but not in TIV. There is evidence of rapid decline of egg-based vaccine effectiveness, particularly in the elderly. Four months after vaccination with egg-based inactivated vaccines, the elderly may not have a protective antibody against influenza virus A(H3N2).4 There was a need to improve the effectiveness of the influenza vaccines, and the level and persistence of the influenza vaccine-induced antibody, particularly in the older adults. For this reason, a radical change had to be introduced.

The JCVI’s findings and considerations

The Joint Committee on Vaccinations and Immunisations (JCVI) looked carefully at the developing situation in the UK and examined evidence that could remedy the problem of low influenza vaccine effectiveness and low persistence of the vaccine-induced influenza antibody.

The JCVI5 was also concerned by the fact that the 2017/18 influenza season was a long season, with peak GP consultation rates the highest seen in England since 2010/11. This was highest in the older age groups and lowest in children. Care homes fared particularly badly. The rate of laboratory-confirmed influenza hospitalisations were also high, according to the JCVI, with peak levels being the highest observed since 2010/11, with the burden particularly notable in the older age groups.

A large proportion of cases were due to influenza B/Yamagata lineage, although previous evidence of cross-protection had been demonstrated when a B lineage circulated, and B/Victoria was in the TIV. The rate of laboratory-confirmed influenza intensive care units (ICU) admissions was very high – the highest peak observed since 2010/11, with the burden again being in the elderly and a large proportion of cases due to influenza B. There were also influenza-confirmed paediatric deaths due to influenza A and B in children up to 17 years of age in England. The JCVI reported that some children had underlying conditions, but others were otherwise healthy. Of those children where the vaccination history was available, none had received the influenza vaccine during the season.

All this was happening despite an increase in vaccination rates in the 2017/18 season in all adult groups in England5 compared to the previous season, with 72.6% of the over 65 year olds, 48.9% of the under 65 year olds in at-risk groups, 47.2% of pregnant women, and 67.6% of healthcare workers being vaccinated (a record over previous years vaccination of HCWs).

In the children’s programme, uptake levels in England5 had increased in all age groups. The vaccine uptake among the 2 and 3 year olds vaccinated by GP practices was 42.6% and 44% respectively. The 4 year olds were targeted in school reception classes and saw a large increase (to 62.6%). The vaccine uptake in England among the 5 year olds (school year 1) was 60.9%, 6 year olds (year 2) achieved 60.3%, 7 year olds (year 3) 57.5%, and 8 year olds (year 4) 55.7%. The uptake in the childhood programme in Scotland and Northern Ireland was higher than in England; they offer the vaccine to all children over the age of 2 years, and in primary schools to age 11 years.

Another difference with England is that if the parents request the injectable QIV, they offer the child the QIV, while in England the QIV is offered as an alternative vaccine, only if the child is in an at risk group.

Using the test negative case control study approach, Public Health England analysed 3,000 respiratory swabs collected across five GP sentinel schemes across the UK;5 1,768 were from controls, 420 cases were A(H3N2), 95 were A(H1N1) and 766 were influenza B/Yamagata. The JCVI pointed out that “most adults would have received TIV which did not contain the influenza B strain that had predominated in the 2017/18 season”.


Vaccinating children has achieved a statistically significant improvement in the children visiting their GP practices with influenza-like illness


The JCVI looked also at the vaccine effectiveness5 (all vaccines used were egg-based). The picture drawn was not so encouraging. For all ages the overall vaccine effectiveness against influenza A and B was modest; against A(H3N2) it was low (among those age 65 years and over as well as those 18 to 64 years of age). Against A(H1N1), the vaccine effectiveness was higher than against A(H3N2) in young adults, but there was not enough evidence to estimate vaccine effectiveness in the elderly. Vaccine effectiveness against influenza B was higher than against A(H3N2), but was considered low.

In the paediatric programme, the overall effectiveness of the intranasal quadrivalent live attenuated influenza vaccine (QLAIV) was moderate; A(H3N2) showed no significant effectiveness, but there was significant effectiveness against A(H1N1pdm09) and against influenza B.

Why such a low vaccine effectiveness against A(H3N2)? The JCVI thought this may be due to the emergence of the A/H3N2 3C2a2 group, and also to egg adaptation generally. The way I would explain this phenomenon is that genetic changes in the vaccine virus hemagglutinin protein that arise during passage in eggs might result in a vaccine immune response that is less effective against circulating viruses. Further, the natural process of immunosenescence play an important role; as we age, we respond less to vaccines (and infections).

Solutions to low vaccine effectiveness

The JCVI5 has considered solutions to the problem of low vaccine effectiveness, particularly in older adults. The process of immunosenescence can be, to a degree, overcome by the use of the adjuvanted trivalent inactivated influenza vaccine (aTIV), which is available this year. In the UK, this vaccine is licensed to be used in older adults, aged 65 years and over. The presence of the adjuvant in aTIV has been to induce higher antibody levels against all strains within the influenza vaccine, the antibodies persist for a longer period than those induced by the non-adjuvanted inactivated influenza vaccines and also induces the production of cross-protective antibodies against unmatched strains when compared against conventional non-adjuvanted TIV.6,7,8 Although aTIV contains influenza B/Victoria, it is expected to give a degree of cross-protection against B/Yamagata that is not in the vaccine this year, although it is not yet known to what degree. In any way, the greater burden on the elderly results from influenza A viruses infection, which the aTIV contains. This makes the aTIV the better vaccine for the 65s and over, according to the JCVI.

The aTIV contains the MF59 adjuvant. This is an oil-in-water emulsion of squalene oil, which is a naturally occurring substance that is found in humans, animals and plants. In humans, it is made in the liver and circulates in the bloodstream. Squalene is also found in a variety of foods, cosmetics, over-the-counter medications and health supplements. The squalene used in pharmaceutical products and vaccines is commercially extracted from fish oil and is then highly purified during the manufacturing process. A single dose of aTIV contains less than 10mg. To put this in context, over 1,000mg of squalene is made in our liver every day, and humans ingest around 50mg to 200mg of squalene every day in a normal diet.

This season’s A(H3N2) vaccine strain has changed from the A/Hong Kong/4801/2014 (H3N2)-like virus to A/Singapore/INFIMH-16-0019/2016 (H3N2)-like virus. This strain of this year’s vaccine is expected to be a better match to circulating strains this season.

The adoption of QIV for all but the 65 years of age and over will reduce the burden of influenza/B viruses, while the widespread vaccination of children with the QLAIV and the use of the aTIV in the 65 year old and over will go a long way in protecting adults, particularly the older adults.

Future solutions to low vaccine effectiveness

There still remains the question of finding ways to improve vaccine effectiveness in the elderly, as well as bypassing the need for growing the influenza viruses in eggs, thus avoiding the consequences of egg adaptation, as well as speeding vaccine production and doing away with the need for fertilised eggs.

Two vaccines are expected to gain UK licensure during this season, with a good chance they will be available for use during the 2019/20 influenza season. The first vaccine is aimed at those age 65 years and older. This is the high-dose inactivated trivalent vaccine (hd-TIV), which uses four times the antigen (60μg instead of 15μg conventional vaccines use). The hd-TIV’s aim is the reduction of the influenza burden in the elderly.

The second vaccine expected to gain UK licensure this year is a cell-culture based quadrivalent vaccine, which aims to address the egg adaptation issue, the need for faster production time and improved vaccine effectiveness.

Vaccines to be used in the current influenza season

This year, NHS England took the important decision to specify which vaccines GPs and community pharmacists should use as well as assure CCGs there will be additional funding to meet demand and cost.9,10 These are the only vaccines to be used in the current influenza season:

  • The adjuvanted trivalent vaccine (aTIV) for all 65s and over. Vaccinators should note that people who have their 65th birthday before 31st March 2019 will be eligible for vaccination, although they may not be 65 when vaccinated. This is an “off label” use of the vaccine allowed by Public Health England (PHE) and incorporated in the relevant Patient Group Direction (PGD).
  • The quadrivalent inactivated vaccine (QIV) for patients in the ‘at risk’ groups aged 18 to under 65 years, including pregnant women.
  • The quadrivalent live attenuated influenza vaccine (QLAIV) for children aged 2 to 17 years.
  • Children aged 6 months to <2 years as well as children aged 2 to 9 years unable to receive the QLAIV because of a contraindication, and also children age 10 to 17 years in the ‘at risk’ groups should receive the QIV that is licensed for this age (not all marketed QIVs are licensed from 6 months). In this case, the QIV used should be obtained directly from PHE via ImmsForm link.

NHS England is more determined than ever to ensure influenza does not adversely affect NHS care and services this winter

There may be situations where the aTIV is not available at a time when an elderly eligible patient presents for vaccination. What is the correct action? NHS England advises that “the patient should be asked to return when it is available”10. This is because the manufacturer of aTIV is staging deliveries in September (40%), October (20%) and November (40%). At the time of writing (October) there were no reported manufacturing shortages of the adjuvanted vaccine for vaccinators that placed their orders on time.

What if aTIV cannot be sourced?

Advise the patient to seek vaccination at other providers where aTIV may be available. If aTIV is found not to be available anywhere in the area, then only in exceptional circumstances, can the QIV can be given.

In this case, the vaccinator must inform the patient that the vaccine (QIV) they are about to receive is not nationally-recommended for them, and also about the possible lower efficacy of the vaccine being offered to them. The patient should also be told why the QIV is being offered instead of the recommended vaccine and why it may still offer protection against seasonal influenza, or attenuate the progression of influenza infection should they get it. Patients should therefore be encouraged to wait until supplies of aTIV are available.

In addition, this discussion should be documented in the individuals’ records.

What about if aTIV needs to be moved from one surgery to another?

The Medicines and Healthcare Products Regulatory Agency (MHRA) has a role in regulating medicines supply. Providers of vaccination services can pass vaccines between them provided a wholesaler licence exists. GPs do not usually hold such a licence. However, the MHRA has confirmed12 that with regards to aTIV recommended for those 65 years and over, it would not prevent supply under the given circumstances of “in short supply” or “no supply” available provided that:

  • The surgery that is holding the excess stock can give an assurance that the vaccine has been held properly in the correct temperature-controlled conditions
  • Confirmed record keeping of temperature monitoring is available
  • The surgery that requests the aTIV is able to verify the assurances given
  • The vaccine can be transported appropriately under the right conditions.

Community pharmacists are able to transfer medicines to other healthcare providers without a wholesaler’s licence under specific circumstances as contained in the relevant guidance.13

Targets for the 2018/19 influenza season

NHS England has set its targets for the current season.14 It is important that GP practices and community pharmacists aim for these targets for the routine influenza vaccination programme:

  • Aged 65 years and over: 75% (this reflects the World Health Organisation (WHO) target for this group)
  • Aged under 65 ‘at risk’, including pregnant women: at least 55% but ideally 75%
  • Preschool children aged 2 and 3 years old (vaccinated by GP practices): at least 48%
  • School aged children aged 4-9 years (in reception class and years 1 to 5): an average of at least 65% to be attained by every provider across all years.

Extension of NHS vaccination programme 2018/19

  • Children aged 9 years (reception class 5) will now be included in the influenza vaccination programme at school
  • Eligible patients registered at the practice who are:15
  • Health and social care staff, employed by a registered residential care/nursing home or registered domiciliary care provider, who are directly involved in the care of vulnerable patients/clients (in a clinical risk group for influenza or who are aged 65 years and over) who are at increased risk from exposure to influenza
  • Health and care staff, employed by a voluntary managed hospice provider, who are directly involved in the care of vulnerable patients/clients (as defined above) who are at increased risk from exposure to influenza.

The eligible health and social care workers/frontline hospice staff should prove their eligibility to a practice or pharmacist. This can be in the form of an ID badge, a letter from their employer or even a recent pay slip. There is no need to prove eligibility if they are 65 years of age and over or in a clinical risk group.

GPs have discretion in recommending NHS influenza vaccination

UK GPs are able to use their discretion in recommending influenza vaccination free on the NHS where they feel it is clinically appropriate. An example is the case where a patient with leukaemia is expected to be discharged from hospital. A GP may decide to vaccinate house-contacts of that patient.

There are also people with difficulties in accessing care, attending appointments, or may not recognise they are eligible for flu vaccination:16

  • People who are homeless or sleep rough
  • People who misuse substances
  • Asylum seekers
  • Gypsy, Traveller and Roma people
  • People with learning disabilities
  • Young people living long-term care.

GPs are able to extend influenza vaccination to such patients.

Last influenza season was long and costly to the NHS in GP consultations, admissions to hospitals and due to the need for increased care in the community. NHS England is more determined than ever to ensure influenza does not adversely affect NHS care and services this winter. For this reason, extra funds have been allocated and specific vaccines have been recommended on the basis of evidence of better effectiveness in the age groups NHS England has suggested they are used.

We are given the opportunity this season to do better; better for our patients, for our hospitals, social services and for us, as primary care professionals. It is within our reach to achieve the proposed targets. Good organisation and adequate provision of vaccination services by GPs and pharmacists can achieve the goal; reduce the influenza burden on our patients and our NHS.


  1. References available online at

Dr George Kassianos, National Immunisation Lead Royal College of General Practitioners and Chair of the RAISE Pan-European Committee on Influenza