Influenza, or the flu, is a seasonal infection that occurs primarily in the winter months in the northern hemisphere and is characterized by the rapid onset of a number of symptoms including fever, chills, aches, pains, coughs and runny nose/nasal congestion. Unlike the common cold, the flu is more severe and can lead to health complications in particular risk groups.

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Risk groups

In the UK, particular risk groups are eligible for free flu vaccination. These include those who are at higher risk of infection from influenza viruses, as well as those who are more likely to develop secondary complications as a result of an infection. Risk groups include:

• Children aged 2 to 10 years of age (nasal vaccine)
• Older people aged 65 or over
• Residential care workers and carers with close contact with compromised individuals
• Pregnant women – vaccination also protects the child up to 6 months of age

Normally, healthy people aged between 10-65 are not eligible for free flu vaccination, however, particular risk groups with chronic illnesses are also eligible:

• Asthma and other respiratory diseases (e.g. COPD)
• Compromised immune system (immunosuppressed) including HIV infection or those undergoing chemotherapy
• Cardiovascular diseases (e.g. CHD, IHD), kidney diseases (e.g. nephrotic syndrome) and liver diseases (e.g. cirrhosis)
• Metabolic diseases (e.g. diabetes mellitus – all types)
• Neurological diseases (e.g. stroke or MS)
• Being clinically obese or having a BMI of 40 or above

Flu viruses

The flu is caused by the influenza virus. There are 3 key types of influenza viruses that affect humans: Influenza A, Influenza B, and Influenza C, of which Influenza A and B are responsible for seasonal flu epidemics. Each year, slightly different changes to the flu viruses due to subtle mutations (mild antigenic drift), lead to new virus strains of seasonal flu.

Influenza A viruses are zoonotic and infect birds and other mammals as well as humans, for example, bird or swine flu. Global epidemics of influenza, known as pandemics, can occur when Influenza A viruses jump the species barrier from birds to humans or in some cases from birds to humans via pigs.

When the virus jumps the species barrier and infects humans this can result in an abrupt substantial change to the virus called an antigenic shift, resulting in the formation of completely new influenza strains unknown to the human immune system. Sometimes these shifts can create strains that are more pathogenic with higher mortality rates than seasonal influenza. These new strains can cause substantial outbreaks that can spread globally resulting in flu pandemics.

The flu vaccine

The flu vaccine is produced annually for each new flu season as the virus strains that are circulating vary each year. This is due to subtle mutations (mild antigenic drifts) within flu viruses that occur more commonly in Type A viruses.

Consequentially, each new flu season is marked by the presence of new altered strains of previously circulating viruses (typically Influenza A and B). As we cannot predict what strains of viruses will be present in the next flu season in the northern hemisphere, vaccines can only be made using data collected on the strains circulating during the previous flu season in both the northern and southern hemispheres.

Children aged 6 months to 2 years usually receive the egg-grown inactivated quadrivalent vaccine (QIVe) containing 4 types of flu strains (of the previous flu season). Children aged 2-17 years of age receive a live attenuated quadrivalent vaccine (LAIV).

Adults aged 18-64 years of age receive a quadrivalent egg-grown (QIVe) or cell-based if allergic to eggs (QIVc) vaccine, again protecting against 4 flu strains. Adults aged 65 or over typically receive an adjuvanted trivalent vaccine (aTIV) protecting against 3 strains of flu – but adjuvanted to make the vaccine more effective.

The flu vaccine contain small amounts of inactivated or live attenuated flu virus particles, small traces of ovalbumin (as the vaccine is typically produced in hens’ eggs), small amounts of sodium and potassium salts to regulate acidity, polysorbate (emulsifier agent), and some vaccines may contain squalene oil (naturally occurring oil that acts as an adjuvant to strengthen the immune response to the vaccine).

As the flu vaccine contains inactivated influenza virus particles, the vaccine itself will not lead to infection, but allow the body’s immune system to begin producing antibodies against it ready to fight future infection. These vaccines typically contain one A(H1N1), one A(H3N2) and 1 or 2 B viruses.

The flu vaccine in the UK is usually given in the run-up to winter (in the autumn between October and November) of each year, as the flu season is typically October (week 40) – April, but it can start early or late depending on the strain. Usually, it can take up to 2 weeks post-vaccination for the vaccine to make you protected against the influenza viruses.

For more serious global flu pandemics (such as the H1N1 pandemic of 2009), flu vaccines may not be effective at all due to substantial antigenic shifts forming completely novel strains of flu viruses that will be resistant to all present strategies.

This is why the death toll of such pandemics is far greater, and also why the virus is able to spread more rapidly due to the lack of innate immunity in the human population. However, as these virus strains continue to circulate in the human population over subsequent years they are likely to have mild antigenic changes such that those that were infected and survived have innate immunity against them, and others will be able to give a vaccine using fragments of these viruses.

Efficacy, safety & side effects

The overall effectiveness of the flu vaccine varies each year. Furthermore, the flu vaccine seems to be more effective in children aged 2-17 years than it is in all ages. It is unclear as to why the flu vaccine is slightly less effective in older adults although the aging of the immune system may have a role to play. However, it does still have efficacy in older adults.

For example, in the UK, in 2016-17 the effectiveness of the flu jab in children aged 2-17 years of age was 66%, but only 40% across all ages. In 2018-19, the effectiveness was 49% in children aged 2-17 years of age and 44% across all ages, due to the introduction of adjuvants in vaccines for over 65 years and thus narrowing the effectiveness gap between ages.

Inactivated flu vaccines are considered safe (as they are typically inactivated). Some people may develop acute side effects including pain, swelling or bruising at the injection site, acute fever, headache, sweating, aching joints, shivering and fatigue. Most people will not develop any side effects; however, the highest number of reported side effects are typically reported in people aged 65 or over receiving the adjuvanted trivalent vaccine (aTIV), Fluad.

Sources:

1. NHS.uk (2020). Flu vaccine overview. https://www.nhs.uk/conditions/vaccinations/flu-influenza-vaccine/  

2. Vaccine Knowledge Project (2020). Inactivated Flu Vaccine. https://vk.ovg.ox.ac.uk/vk/inactivated-flu-vaccine  

Further Reading

• All Influenza Content
• Influenza – What is Influenza?
• Types of Influenza
• Influenza Epidemiology
• Influenza Prognosis

Written by

Osman Shabir

Osman is a Neuroscience PhD Research Student at the University of Sheffield studying the impact of cardiovascular disease and Alzheimer's disease on neurovascular coupling using pre-clinical models and neuroimaging techniques.