Preventing Influenza and the Role of Adjuvanted Vaccines – Seqirus Vaccines Ltd

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Preventing Influenza and the Role of Adjuvanted Vaccines An Annual Event That Affects Lives How a Healthcare System Can Cope with a Flu Outbreak More Effective Vaccine Saves Lives and Money Key Selection Factors Today and What the Future Holds

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A flu vaccine that works better for my age group?

About time!

For a strong response in people aged 65 years and older.

FLUAD® is the 1st and only adjuvanted seasonal flu vaccine available in the UK1

For questions about Seqirus and FLUAD®, please contact the Seqirus team on 01530 454288, flu.salesuk@seqirus.com or visit www.seqirus.com Copyright © Seqirus UK Limited 2017. UK/FLUD/0917/0030 October 2017 Reference: 1. FLUAD® Summary of Product Characteristics.

Prescribing Information Fluad® suspension for injection in pre-filled syringe Influenza Vaccine (surface antigen, inactivated, adjuvanted with MF59C.1) Presentation: Each 0.5ml of Fluad® contains 15 micrograms of each of three purified influenza virus antigens prepared from the strains of influenza virus that comply with the WHO recommendations (Northern Hemisphere) and EU decision for the 2016/17 season: A/California/7/2009 (H1N1) pdm09-like strain (A/California/7/2009, NYMC X-181) 15 micrograms haemagglutinin, A/Hong Kong/4801/2014 (H3N2)-like strain (A/Hong Kong/4801/2014, NYMC X-263B) 15 micrograms haemagglutinin, B/Brisbane/60/2008-like strain (B/Brisbane/60/2008, wild type) 15 micrograms haemagglutinin, with adjuvant MF59C.1 (9.75mg squalene, 1.175mg polysorbate 80, 1.175mg sorbitan trioleate, 0.66mg sodium citrate, 0.04mg citric acid, water). Indications: Active immunisation against influenza in the elderly (65 years of age and over), especially for those with an increased risk of associated complications. Dosage and Administration: Intramuscular injection into the deltoid muscle using a 1-inch needle. Adults aged 65 years and over: Single dose 0.5ml. Contra-indications: Hypersensitivity to the active substances, components of the adjuvant, excipients, to chicken or egg proteins (such as ovalbumin), kanamycin, neomycin sulphate, formaldehyde, cetyltrimethylammonium bromide (CTAB), barium sulphate, or in anyone who has had an anaphylactic reaction

to previous influenza vaccination. Immunisation shall be postponed in patients with febrile illness or acute infection. Warnings and Precautions: Appropriate medical treatment and supervision should be readily available in case of an anaphylactic event following administration. Do not inject intravascularly or subcutaneously. Endogenous or iatrogenic immunosuppression may result in insufficient antibody response. Latexsensitive individuals: Although no natural rubber latex is detected in the syringe tip cap, the safe use of Fluad® in latex-sensitive individuals has not been established. Interactions: No clinical data on concomitant administration with other vaccines are available. If Fluad® needs to be used at the same time as another vaccine, immunisation should be carried out on separate limbs. It should be noted that the adverse reactions may be intensified. Pregnancy and Lactation: Not applicable.

Effects on ability to drive and use machines: Fluad® has no or negligible influence on the ability to drive and use machines. Side Effects: The most common reactions are headache, myalgia, injection site pain and tenderness, fatigue, nausea, diarrhoea, vomiting, sweating, arthralgia, fever, malaise, and shivering; local reactions include redness, swelling, ecchymosis, and induration. Uncommon reactions include rash. The following have been reported post-marketing: thrombocytopenia, lymphadenopathy, asthenia, influenza-like illness, extensive swelling

of injected limb, injection-site cellulitis-like reaction, allergic reactions including anaphylactic shock (in rare cases), anaphylaxis, angioedema, vasculitis with transient renal involvement, and neurological disorders such as encephalomyelitis, Guillain-Barré syndrome, convulsions, neuritis, neuralgia, paraesthesia, syncope, and presyncope. Overdose: Overdosage is unlikely to have any untoward effect. Legal Category: POM. Package Quantities: Packs of 1 or 10 pre-filled syringes. Marketing Authorisation Number: UK: PL 46752/0001. Basic NHS Cost: £9.79 per 0.5ml pre-filled syringe, £97.90 per 10 pack. Marketing Authorisation Holder: Seqirus S.r.l., Via Fiorentina 1, 53100 Siena, Italy For full prescribing information and details of other side effects see the Summary of Product Characteristics at www.gov.uk/pil-spc Date of preparation: September 2017 UK/FLUD/0717/0015(1) ® Registered trade mark Seqirus S.r.l, Italy Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard.

Adverse events relating to Seqirus products should also be reported to Seqirus UK Limited on 01748 828816

PREVENTING INFLUENZA AND THE ROLE OF ADJUVANTED VACCINES

SPECIAL REPORT

Preventing Influenza and the Role of Adjuvanted Vaccines An Annual Event That Affects Lives How a Healthcare System Can Cope with a Flu Outbreak

Contents

More Effective Vaccine Saves Lives and Money Key Selection Factors Today and What the Future Holds

Foreword

2

John Hancock, Editor

An Annual Event That Affects Lives

3

John Hancock, Editor

What is Influenza?

Published by Global Business Media

Prevalence of Influenza

Published by Global Business Media

The Impact of Influenza on Lives

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How a Healthcare System Can

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5

Cope with a Flu Outbreak Peter Dunwell, Medical Correspondent

Impact of Influenza on the NHS

Publisher Kevin Bell

NHS Managing the Campaign

Business Development Director Marie-Anne Brooks

Vaccines That Effectively Match the Challenge

Editor John Hancock Senior Project Manager Steve Banks Advertising Executives Michael McCarthy Abigail Coombes Production Manager Paul Davies For further information visit: www.globalbusinessmedia.org

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While every care has been taken in the preparation of this publication, neither the Publishers nor the Editor are responsible for such opinions and views or for any inaccuracies in the articles.

Adjuvanted Vaccines Offer Broader Protection

More Effective Vaccine Saves Lives and Money

7

Camilla Slade, Staff Writer

Vaccine Effectiveness What is an Adjuvant?

The Benefits of Using an Adjuvant Like MF59

Key Selection Factors Today

9

and What the Future Holds

John Hancock, Editor

Key Factors to Consider When Ordering Flu Vaccine Future Outlook for Influenza Vaccine Research Conclusion

References 11

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PREVENTING INFLUENZA AND THE ROLE OF ADJUVANTED VACCINES

Foreword

T

HE FLU season: it sounds innocuous and yet

that it can have on people who catch it. Building

estimates suggest that globally up to half a

on that, Peter Dunwell looks first at the impact of

million people die each year from various types of

influenza on the National Health Service (NHS) and

influenza. And that ‘various types’ factor is one of

how the service manages its response to an outbreak

the key reasons why flu can be much more serious

of flu. He also looks at vaccines considering both

than it is sometimes regarded because each year’s

the clinical effectiveness of adjuvanted vaccines and

strain will have evolved from the previous year

how they can offer broader protection. Camilla Slade

with, often, several variants in any one year. Added

looks at the development of adding adjuvants to

to that, different groups in society are at different

vaccines, the significance of this and how adjuvants

degrees of risk for contracting flu and for the effect

can enhance the effectivity of vaccines in a number

it could have on them. A killer in its own right, flu

of ways that will improve the outcomes for particular

can cause pneumonia and exacerbate potentially

‘at risk’ groups. Finally, we look at the process of

fatal conditions such as pneumonia or heart disease.

preparing a healthcare practice for the flu season

Prevention is better than cure and a great deal of

and selecting vaccines as well as the future outlook

effort goes into devising, improving and updating

for further improvements in flu vaccines, including

flu vaccines to try and minimise the impact of that

the possibility of a universal vaccine.

annual flu season.

This paper starts with an article about influenza, its prevalence in the population and some of the impacts

John Hancock Editor

John Hancock has been an Editor of Primary Care Reports since launch. A journalist for nearly 30 years, John has written and edited articles, papers and books on a range of medical, management and technology topics. Subjects have included management of long-term conditions, elective and non-elective surgery, Schizophrenia, health risks of travel, local health management and NHS management and reforms. He also writes on IT applications (including AI and AR) in work related processes.

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PREVENTING INFLUENZA AND THE ROLE OF ADJUVANTED VACCINES

An Annual Event That Affects Lives John Hancock, Editor Influenza seems to arrive each year and poses many challenges for those afflicted and for the authorities charged with tackling it

E

VERY AUTUMN there is a flurry of news about the anticipated ‘Winter Flu Epidemic’, but familiarity should not trick us into underestimating its potential for real harm. “Influenza is associated with a high mortality and morbidity in older adults.”1 is how the Elsevier article ‘The comparative effectiveness of adjuvanted and unadjuvanted trivalent inactivated influenza vaccine (TIV) in the elderly’ puts it. But there is hope: the article continues, “Vaccination remains the most effective method of preventing influenza and its consequences. However, vaccine effectiveness decreases with increasing age and increasing immunosenescence.” So, the more likely you are to be harmed by flu, the less effective conventional vaccines become.

But, the article explains, “In older adults, immunogenicity studies suggest an MF59 adjuvanted influenza vaccine… may help.”

What is Influenza?

So, what is influenza? Most readers will certainly have experienced the condition at some time, but the Center for Disease Control and Prevention neatly sums it up as2, “The flu is a contagious respiratory illness caused by influenza viruses that infect the nose, throat, and sometimes the lungs. It can cause mild to severe illness, and at times can lead to death. The best way to prevent the flu is by getting a flu vaccine each year.”

However, this perennial condition has a trick up its sleeve which is that it changes from year to year; so this year’s flu may not be the same as last year’s strain, plus there might be more than one strain of the disease circulating at any given time. Even that is not the full extent of its armoury because influenza can spread either as a “virus laden aerosol”3, i.e. sneezing, or even on routinely handled and touched objects like keyboards and door handles.

Prevalence of Influenza Globally, the prevalence of influenza is considerable with, according to WHO (World

Health Organisation)4, 3.5 million cases a year resulting in 250,000 to 500,000 deaths.

As well as being a health risk, influenza has a social and economic impact, especially for the healthcare system. “In the UK an average of 600 people a year die from complications of flu, but in some years, this can rise to over 10,000 people. Flu leads to hundreds of thousands of GP visits and tens of thousands of hospital stays a year.” That summary of UK influenza prevalence is from the Oxford Vaccine Group’s5 ‘Vaccine Knowledge Project’.

Given the high levels of prevalence and its economic significance, governments keep records to help understand any patterns in and try to predict future trends with influenza outbreaks. In the UK, this responsibility sits with Public Health England (PHE) to both record and review the evidence from past outbreaks and to advise UK Health Departments on future immunisation programmes based on prevalence figures6.

The committee’s conclusions for the 2016-2017 influenza season recorded their disappointment that vaccine effectiveness for those aged 65 or older had been lower than in previous years.

However, it was noted that, for the over 65 group, “new influenza vaccines, including an adjuvanted vaccine” would be available to order for the 2018/19 flu season. The influenza vaccination programme is not a homogenised process but targets different vaccines with different attributes at identified groups in the population and especially groups at higher risk of severe disease.

Although the elderly, pregnant women and those with other complicating conditions are certainly at risk, there is also a paediatric programme aimed at different groups of children and young people.

Demonstrating this reach across the population and the complexity of the phenomenon, the Journal of Infection 2013 survey on ‘The burden of influenza in England by age and clinical risk group: A statistical analysis to inform vaccine policy’7 concludes, “Influenza accounted for ~10% of the attributed respiratory admissions

The flu is a contagious respiratory illness caused by influenza viruses that infect the nose, throat, and sometimes the lungs.

It can cause mild to severe illness, and at times can lead to death.

The best way to prevent the flu is by getting a flu vaccine each year

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PREVENTING INFLUENZA AND THE ROLE OF ADJUVANTED VACCINES

Vaccine effectiveness for those aged 65 or older had been lower than in previous years. However, it was noted that, for the over 65 group, “new influenza vaccines, including an adjuvanted vaccine” would be available to order for the 2018/19 flu season

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and deaths in hospital. Healthy children under five had the highest influenza admission rate (1.9/1000). The presence of co-morbidities increased the admission rate by 5.7 fold for 5–14 year olds (from 0.1 to 0.56/1000), the relative risk declining to 1.8 fold in 65+ year olds (from 0.46 to 0.84/1000). The majority (72%) of influenzaattributable deaths in hospital occurred in 65+ year olds with co-morbidities. Mortality in children under 15 years was low with around 12 influenzaattributable deaths in hospital per year in England; the case fatality rate was substantially higher in risk than non-risk children. Infants under 6 months had the highest consultation and admission rates, around 70/1000 and 3/1000 respectively.”

There is a very detailed breakdown of prevalence by age, gender and even means of travel to work, in the Influenzanet annual Flusurvey using data from Public Health England and the London School of Hygiene and Tropical Medicine8. This tracks incidence throughout the flu season and shows that, in the 2015/16 season, prevalence peaked at 8 cases per week, per 1,000 of the population overall.

The efficacy and reach of the vaccination programme can significantly affect prevalence and outcomes. For instance, an increase in the death rate in 2015 over 2014 was attributed by

Dr Richard Pebody, head of flu surveillance for PHE (Public Health England) to a mismatch between the A(H3N2) influenza strain used to make the vaccine and the main strain that spread in the UK last [2014] winter9. The strain identifiers are vital in matching vaccines to the likeliest strain in the next season.

The Impact of Influenza on Lives Perhaps the most obvious effect of influenza on people’s lives is in the illness itself and the consequent disruptions to family and work lives or worse, “Increasing age, particularly over 70 years, brings further increases in the risk of all-cause mortality or hospitalisation with influenza or pneumonia”. Also, “In addition to causing deaths from acute influenza illness and secondary bacterial pneumonia, influenza has been associated with increased mortality from ischaemic heart disease, cerebrovascular disease, and diabetes. Up to 90% of influenzarelated deaths occur in persons aged 65 years or older.” Both these statements from the article cited at the start of this article.

In the next article, we’ll look at the impact of influenza on the NHS and the relative efficacies of different vaccines.

PREVENTING INFLUENZA AND THE ROLE OF ADJUVANTED VACCINES

How a Healthcare System Can Cope with a Flu Outbreak Peter Dunwell, Medical Correspondent The combined pressures to deal with an outbreak and prevent the next one

Impact of Influenza on the NHS We have grown used to autumn predictions about the impact on the NHS of the oncoming winter’s ‘flu epidemic’. However, in the light of past experience, those predictions all too often are accurate. The introduction to Elsevier’s report, ‘Comparison of the safety and immunogenicity of an MF59®-adjuvanted with a non-adjuvanted seasonal influenza vaccine in elderly subjects.’ states, “The largest impact of seasonal influenza is seen in the elderly (≥65 years), with the highest rates of mortality and hospitalisations reported in this age group.” This is important because, in the UK, those hospitalisations impose both cost and service denial burdens on the NHS. Public Health England (PHE) maintains a close brief on influenza outbreaks as the impact can affect a range NHS services. PHE’s brief includes ‘Surveillance of influenza and other respiratory viruses in the United Kingdom Winter 2015 to 2016’10 which reported, “…a consistent pattern of numerous outbreaks in hospitals, high numbers of admissions to hospital and ICU/HDU…” This suggests that the highest care capabilities (ICU/ HDU) can be, in part at least, occupied with flu patients and therefore unavailable for other conditions such as following surgery. Not only is the NHS coping with increased admissions but also cases do occur in hospitals, among patients and staff. And, when staff numbers are reduced by the effects of an outbreak, the service will be even less able to cope with additional admissions resulting from the wider outbreak.

NHS Managing the Campaign The impact on the NHS relates directly to the impact on people with influenza because those most vulnerable groups such as older people, pregnant women and people with underlying health conditions will all need to access NHS services unless they have been protected against influenza, and that means being vaccinated.

Also, for anyone who develops some of the

complications that can accompany flu, such as bronchitis and pneumonia, the NHS will have to deploy even more specialist services than the influenza alone might require.

The other side of the NHS coin is that the service has to endeavour to pre-empt any outbreak and that means organising vaccinations. As well as the management challenge there is also a cost involved. NHS England has already unveiled its campaign for the 2017/18 flu season11, which details the steps to be taken including the vaccination of NHS staff themselves. And, on top of that is the pressure to ensure as much as possible that the vaccine deployed in a season is matched to the strain of influenza most likely to prevail that season. The NHS manages this by looking around the world at comparable societies who are into the season before the UK12. Also, the NHS in England has made plans to free up 2,000 beds for the 2017/18 flu season but that will mean 2,000 less beds will be available for all the other procedures that the serviced undertakes. And it will compound the continuing bed-blocking problem with, often elderly, people unable to be admitted because there are no facilities to accept them.

Estimates as to the financial cost of an outbreak of influenza are hard to isolate but it has been estimated that the cost of preparing for the swine flu pandemic, that didn’t materialise, was in the region of £1.2bn in 2010, so one can be sure that the cost of preparation for and dealing with an actual outbreak of any strain of influenza will be very high. All of this points to the need for an effective vaccination programme that can cope with the year-on-year evolution of the influenza threat.

The largest impact of seasonal influenza is seen in the elderly (≥65 years), with the highest rates of mortality and hospitalizations reported in this age group

Vaccines That Effectively Match the Challenge The American Journal of Epidemiology (AJE) 2012 paper about a study conducted on influenza vaccines opens with, “Although vaccination WWW.PRIMARYCAREREPORTS.CO.UK | 5

PREVENTING INFLUENZA AND THE ROLE OF ADJUVANTED VACCINES

The other side of the NHS coin is that the service has to endeavour to pre-empt any outbreak and that means organising vaccinations.

As well as the management challenge there is also a cost involved.

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against influenza is recommended for elderly and high-risk patients in many countries, efficacy in the elderly has been suboptimal. The MF59 adjuvanted trivalent inactivated vaccine (aTIV) was developed to increase the immune response of elderly subjects to influenza vaccination, but its effectiveness has not yet been well documented.” However, adjuvanted flu vaccines have considerable effectiveness data e.g. JCVI JUN17 minute - published studies indicated higher vaccine immunogenicity and effectiveness for the adjuvanted vaccines compared with non adjuvanted vaccine. A trivalent influenza vaccine is defined by the NCI dictionary as ‘A synthetic vaccine consisting of three inactivated influenza viruses… Trivalent influenza vaccine is formulated annually based on influenza strains projected to be prevalent in the upcoming flu season.’

Published in 2013, an Elsevier paper on ‘The comparative effectiveness of adjuvanted and unadjuvanted trivalent inactivated influenza vaccine (TIV) in the elderly’ was able to shed further light on the effectiveness. “In the winter of 2011–12 in British Columbia, an adjuvanted sub-unit trivalent influenza vaccine showed superior vaccine effectiveness against laboratory confirmed influenza than the split virion unadjuvanted vaccine.” The same paper continued further to add, “Clinical trials have also shown that MF59 adjuvanted vaccines are more immunogenic than conventional nonadjuvanted vaccines and also provide better immunogenicity against drifted seasonal strains that are different

from the virus strains included in the vaccine.”

While the paper does not claim that adjuvanted vaccine is the whole answer for elderly patients with immunosenescence, the study on which it is based found, “adjuvanted vaccine appeared to be a significant improvement on the protection available against the known hospitalizations and death in this group.”

Adjuvanted Vaccines Offer Broader Protection The AJE paper cited above reinforces the point about adjuvanted vaccines providing “better immunogenicity against drifted strains [of the flu virus]” adding that, “Italian guidelines on the prevention and control of influenza provide free access to vaccines for high-risk persons, with adjuvanted vaccines generally preferentially recommended for more frail high-risk individuals.”

In a similar vein, Science Daily13 in September 2017, suggested that it is not only the elderly who would benefit. The article calls for “clinical trials of the high-dose and new recombinant trivalent influenza vaccines in 50- to 64-year-old adults with chronic illnesses, such as heart or lung disease, diabetes, or cancer, to determine if they do provide considerably better protection than the currently recommended standard dose quadrivalent vaccine.”

With a condition such as influenza and given the costs an outbreak can generate, any advance in the quality of a vaccine or its ability to cope from strain to strain must be an improvement.

PREVENTING INFLUENZA AND THE ROLE OF ADJUVANTED VACCINES

More Effective Vaccine Saves Lives and Money Camilla Slade, Staff Writer When the NHS has to manage an outbreak of influenza, reducing the case load, especially of complex cases, will have all-round benefits.

Vaccine Effectiveness “Vaccination is the most effective method to prevent influenza infection. However, current influenza vaccines have several limitations.

Relatively long production times, limited vaccine capacity, moderate efficacy in certain populations and lack of cross-reactivity are important issues that need to be addressed.”

These are the opening words for the 2015 Science Direct paper, ‘Current and next generation influenza vaccines: Formulation and production strategies.’14 Further on, the paper adds, “Enhancing the immunogenicity of vaccine antigens by the addition of adjuvants has several advantages, such as dose sparing, increased efficacy in the elderly, unprimed individuals and immunocompromised, and broadening of the influenza-specific immune response… The development of suitable adjuvants for influenza vaccines is therefore imperative.”

It’s much the same with the comment in the Elsevier Vaccine paper, ‘Comparison of the safety and immunogenicity of anMF59®-adjuvanted with a non-adjuvanted seasonal influenza vaccine in elderly subjects.’ “Conventional nonadjuvanted seasonal trivalent influenza vaccines have been shown to perform inadequately in elderly subjects. In previous studies, MF59adjuvanted vaccines (aTIVs) have demonstrated increased immunogenicity, providing increased vaccine effectiveness in older adults.” The reason this matters is that, as people age, their immune competence declines making vaccine effectiveness also decline. Add to that the fact, already covered, that virus strains might vary from year to year and it can be seen that a different approach to these types of vaccine might well improve or save lives and save costs for healthcare systems such as the NHS. In the American Journal of Epidemiology paper following a study in Northern Italy, it was concluded that vaccination with aTIV (adjuvanted trivalent inactivated influenza vaccine) reduced the risk of hospitalisation of elderly people for

influenza or pneumonia by 25% compared with vaccination with TIV, the traditional nonadjuvinated vaccine. The ‘Comparison of safety…’ paper cited above also includes, “The immunogenicity of aTIV at Day 22 [of the study] was significantly higher… than TIV… in both the entire study population and the highrisk group.” Other studies have agreed and found that the additional effectiveness of aTIVs can still be maintained some months after vaccination. But in the above paper again, “In general, at six months (Day 181) and one year (Day 366) after vaccination, the subjects in the aTIV group (N = 189) had slightly higher GMTs and seroprotection rates than the TIV subjects (N = 191) against all strains.”

What is an Adjuvant?

Throughout this paper we have been referring to differences between adjuvanted and nonadjuvanted vaccines but, the reader might ask, what is an adjuvant and why are adjuvants added to vaccines. The Center for Disease Control and Prevention defines an adjuvant as15, “… an ingredient of a vaccine that helps create a stronger immune response in the patient’s body.

In other words, adjuvants help vaccines work better. Some vaccines made from weakened or dead germs contain naturally occurring adjuvants and help the body produce a strong protective immune response. However, most vaccines developed today include just small components of germs, such as their proteins, rather than the entire virus or bacteria. These vaccines often must be made with adjuvants to ensure the body produces an immune response strong enough to protect the patient.”

In fact, adjuvants in vaccines are nothing new and have been used for more than 70 years to improve the body’s immune response which, as well as being a good thing in itself, can also allow for lower amounts of inactivated virus or bacteria to be used in a vaccine.

One adjuvant mentioned in this paper is MF59,

Conventional nonadjuvanted seasonal trivalent influenza vaccines have been shown to perform inadequately in elderly subjects. In previous studies, MF59-adjuvanted vaccines (aTIVs) have demonstrated increased immunogenicity, providing increased vaccine effectiveness in older adults

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PREVENTING INFLUENZA AND THE ROLE OF ADJUVANTED VACCINES

Most vaccines developed today include just small components of germs, such as their proteins, rather than the entire virus or bacteria.

These vaccines often must be made with adjuvants to ensure the body produces an immune response strong enough to protect the patient

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an oil-in-water emulsion that is found to boost the body’s response to a vaccine such as an aTIV.

The Benefits of Using an Adjuvant Like MF59 The benefits of adjuvanted vaccines have already been covered above and they are based around improved efficacy in older people. Since their first use in 1997, several studies have endorsed this benefit which can be accredited to stimulating a higher antibody response than would be the case with traditional vaccines. And it isn’t only the elderly who benefit from this effect. According to the paper, ‘Comparison of the safety…’ cited above, other age groups at high risk from influenza complications can benefit. The paper highlights a study that had shown that, “aTIV was shown to have an overall efficacy of 75% compared with 2% from a non-adjuvanted TIV in 6 to ≤24 month old children.”

Another benefit, again addressed in previous articles, is that adjuvanted vaccines have been shown to stimulate a persistent antibody response that could well improve their performance, compared to non-adjuvanted vaccines, over the longer term as strains of influenza adapt to the current vaccine. Adjuvant can enhance the effectiveness of a vaccine for older people and for those at higher risk or with chronic heart and /or lung conditions. But many

older people also fall into other high risk groups having long-term health complications or comorbidities. Where such additional complications exist, influenza attributed mortality rates have been estimated to be some twenty times more likely than in cases where the complications are absent. That improved antibody response over several studies suggests that aTIV might provide more effective protection than conventional TIVs in elderly subjects with co-morbidities.

There seems to be a growing body of research, the conclusion of which has been that, for patients in higher risk groups and / or with longterm co-morbidities, using adjuvanted vaccines will be more effective in combatting any influenza outbreak and that will have tremendous knock-on benefits for the lives of the people in question and for the NHS, which will find itself better able to manage if less influenza patients, and especially less of them whose other conditions will make them in need of more treatment, have to come into the system during the flu season.

The UK will be licensing an aTIV flu vaccine in 2017 and was, at the time of writing, looking to bring forward a plan to introduce that vaccine into the immunisation programme for the over 65year-old group in the population. In fact, aTIV is available to order for the 2018/19 flu season.

PREVENTING INFLUENZA AND THE ROLE OF ADJUVANTED VACCINES

Key Selection Factors Today and What the Future Holds John Hancock, Editor Practices need a plan for each flu season and researchers have a plan for long term success

N

ONE OF what is in the previous articles can change one very important factor; as part of their preparations for the winter flu season, practice clinicians will have to choose and order their supplies of vaccine. But, given that there is a choice and given that different practice populations will vary this is, as with most things in healthcare, becoming an ever more complex process. Also, nothing stays the same. So, this year’s appropriate choice will not simply be able to be repeated for future years. The practice population might change, the anticipated influenza strain will change and there will be developments in vaccine formulation and technology that have to be taken into account.

Key Factors to Consider When Ordering Flu Vaccine Who is at risk?

A number of ‘at risk’ groups have been identified.

Anyone in the population can become infected with and suffer influenza but, according to NCBI15, “… influenza infection can lead to serious complications, particularly in certain populations.

These ‘at-risk’ groups include pregnant women, children aged less than 5 years (especially those aged <2 years… the elderly (≥65 years of age), and those with chronic medical conditions.”

The details have been included in my colleagues’ articles but healthcare practices will need to understand how that ‘at risk’ factor affects their practice and whether any particular group would fare better being administered a vaccine with qualities known to improve resistance in that group.

Age groups Almost the same as the ‘at risk’ factor are the age groups served by a practice. However, practice managers might also consider the need to protect health service workers themselves for as long as possible and regardless of age.

Eligibility Broadly the ‘at risk’ groups and some age groups are eligible to be covered in the national vaccination programme, although anyone can buy themselves a vaccination.

If clinicians need any guidance on eligibility issues and what types of vaccine might be suitable, The Department of Health and Public Health England16 publish a programme for the coming flu season in about March so that practices have plenty of time to plan. The programme includes guidance as to which vaccines or vaccine types will be suitable for different groups right down to whether a vaccine contains egg – no good for patients with an allergy. In fact, it is generally important to take into account any other conditions that might affect a patient.

Likelihood of the infection spreading Some groups such as care home residents or schoolchildren (and staff in both cases) will spend most of their time in an enclosed environment with a very high risk of infection spread: the more of them that are vaccinated and the earlier, the better.

Practices will need to understand how that ‘at risk’ factor affects their practice and whether any particular group would fare better being administered a vaccine with qualities known to improve resistance in that group

Latest studies Practice clinicians responsible for selecting vaccines to be used in the next flu season should familiarise themselves with the latest developments from papers such as those cited in this paper.

Cost It isn’t a factor that we like to think of in terms of healthcare but, in a world of finite resources, cost cannot be ignored. But it isn’t simple because, sometimes what might seem an initially more expensive solution will offer a range of effectiveness that makes it less costly overall. Cost effectiveness rather than just cost is what matters.

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PREVENTING INFLUENZA AND THE ROLE OF ADJUVANTED VACCINES

Adjuvanted vaccines have been shown to stimulate a persistent antibody response that could well improve their performance, compared to non-adjuvanted vaccines, over the longer term as strains of influenza adapt to the current vaccine Make a plan Not strictly a factor in choosing vaccines, but nonetheless very important, is for the practice to make a plan for a vaccination programme which addresses most of the eligible groups with appropriate vaccines as early as possible but also takes account of the fact that some people will become eligible during the season and so might need vaccination later. This could apply where a woman not previously in an eligible group becomes pregnant.

NHS England encourages community pharmacies to undertake flu vaccination programmes to reduce the load on general practice clinicians. It also offers guidance in the form of a Service Specification publication17 which gives guidance on how to proceed and on practical issues such as safe storage of vaccines and stock management, to ensure that no vaccine is used after its expiry date.

Future Outlook for Influenza Vaccine Research Research into influenza, its genesis and how to avoid and/or combat it is continual even as new strains (often named after the species in which they were first identified) emerge every year.

A universal vaccine One key objective of research is a universal flu vaccine that can cope with most strains identified to date and, more importantly, have the capability to build defence against possible future evolutions. A collaborative research programme involving universities of Lancaster, Aston and Complutense in Madrid has

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employed computational techniques to design just such a universal vaccine, as reported in Science Daily18. In fact, “researchers have devised two universal vaccines; a USA-specific vaccine with coverage of 95% of known US influenza strains; and a universal vaccine with coverage of 88% of known flu strains globally.”

The importance of this development can be gauged from the cost when previous strains have gone unchecked. Pandemics in 1918, 1957 and 1968 led to millions of deaths.

And, at any time, annual flu epidemics are estimated to cause up to half a million deaths globally according to the World Health Organisation. A universal vaccine would target that part of the flu virus that does not change from strain to strain.

Needle phobia OK, it might not be that extreme but many people have a dislike of being injected and so might put off any vaccination until it’s too late.

A development reported in The Telegraph19 this year has been a new skin patch delivery system which has been trialled delivering flu vaccine.

Despite being in the ‘at risk’ group, fewer than 50 per cent of pregnant women in the UK accepted flu vaccinations in the winter of 2016/17 and it is hoped that the patch delivery might improve this number.

Conclusion The battle against an adaptable virus such as influenza is not likely to be over soon but might well be won eventually with a combination of more effective and more broadly effective vaccines.

PREVENTING INFLUENZA AND THE ROLE OF ADJUVANTED VACCINES

References: 1

Article, ‘The comparaTIVe effectiveness of adjuvanted and unadjuvanted trivalent inactivated influenza vaccine (TIV) in the elderly’

http://bit.ly/2y4I0hL 2

Center for Disease Control and Prevention www.cdc.gov/flu/keyfacts.htm

3

News Medical www.news-medical.net/health/What-is-Influenza.aspx

4

NIAID NIH www.who.int/immunization/research/forums_and_initiaTIVes/1_BGraham_Universal_Flu_Vaccine_Develop_gvirf16.pdf?ua=1

5

Oxford Vaccination Group vk.ovg.ox.ac.uk/influenza-flu

6

UK ‘The national flu immunisation programme 2017/18’

nhs-digital.citizenspace.com/rocr/r01193-17a/supporting_documents/R01193annual_flu__letter_2017to2018.pdf

7

Copy Website link

8

Flusurvey flusurvey.org.uk/en/results/

9

The Guardian www.theguardian.com/uk-news/2016/apr/07/number-deaths-england-wales-12-year-high-life-expectancy

10

Public Health England www.gov.uk/government/uploads/system/uploads/attachment_data/file/526405/Flu_Annual_Report_2015_2016.pdf

11

NHS England www.england.nhs.uk/2017/10/nhs-leaders-unveil-action-to-boost-flu-vaccination-and-manage-winter-pressures/

12

The Telegraph www.telegraph.co.uk/news/2017/09/12/nhs-fears-worst-flu-season-history/

13

Science Daily www.sciencedaily.com/releases/2017/09/170921121139.htm

14

Science Direct www.sciencedirect.com/science/article/pii/S0939641115002556

15

NCBI www.ncbi.nlm.nih.gov/pmc/articles/PMC4974050/

16

UK ‘The national flu immunisation programme 2017/18’

nhs-digital.citizenspace.com/rocr/r01193-17a/supporting_documents/R01193annual_flu__letter_2017to2018.pdf 17

NHS England www.england.nhs.uk/wp-content/uploads/2017/08/17-18-service-specification-seasonal-flu.pdf

18

Science Daily www.sciencedaily.com/releases/2016/09/160930085814.htm

19

The Telegraph www.telegraph.co.uk/women/life/flu-jab-pill-microneedle-patches-future-medicine/

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PREVENTING INFLUENZA AND THE ROLE OF ADJUVANTED VACCINES

Notes:

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