A brief guide to immunisation and the immunocompromised child or young person

A healthy immune system protects the body against infections, fights infections when they occur and supports tissue repair following damage. The immune system is made up of a network of organs, cells, and proteins that work together to generate immune responses when pathogens enter the body (Simon et al, 2015; Davies et al, 2021).

There are two parts to the immune system: the innate system and the acquired system. Innate immunity is the body's natural defence system, which includes physical barriers such as the skin. Acquired immunity occurs when the body produces or receives antibodies, through exposure to disease or infection or through vaccination (Warburton, 2018). Vaccines can either contain weakened or inactive antigens or mRNA coding for the antigen that triggers an immune response within the body. This causes the white blood cells to produce complementary antibodies and memory cells. The antibodies target and attach to the antigen, allowing for phagocytosis. Regardless of whether the vaccine is made up of the antigen itself or its mRNA it will not cause the disease in the person receiving the vaccine, but it will prompt their immune system to respond much as it would have on its first reaction to the actual pathogen (World Health Organization (WHO), 2020).

Immunosuppression and its effect on previously vaccinated children

During immunosuppression, the normal function of the immune system is inhibited. Treatments, such as chemotherapy, disrupt the normal function of the cell cycle, which consequently causes immunosuppression. Red blood cells, platelets and white blood cells are affected and diminished. Neutrophils, a type of white blood cell, are the most abundant leukocytes in the circulation, and are the first line of defence in the innate immune system (Rosales, 2018). Children who are immunocompromised can sometimes have low levels of neutrophils due to their condition or treatments and become neutropenic. Neutropenia is a rare disorder that causes a lower than normal level of neutrophils; it can be a very serious condition because, without a sufficient volume of neutrophils, a child is susceptible to bacterial infections that can become life-threatening (Price and Coulson, 2018).

It is important to consider the safety of vaccines for immunocompromised children, for example, because live vaccines (such as the live flu vaccine) use a weakened form of the pathogen and this can cause significant harm to immunocompromised children. However, there are alternative non-live flu vaccines available. One study found that 40% of solid organ transplant recipients were hospitalised with vaccine-preventable flu cases (Feldman et al, 2019); therefore, the risks of being unvaccinated are substantial.

Guidelines are available for specific vaccines and changes to dosing regimens in immunocompromised children (Garland et al, 2017). Investigations into higher dose vaccinations for immunocompromised children are currently ongoing, however current evidence in paediatrics is limited (Lai et al, 2019).

Caldera et al (2019) found that patients undergoing immunosuppressive treatment for inflammatory bowel disease still had sufficient protection again measles, mumps and rubella when vaccinated prior to commencing treatment. Another study found immunomodulators and anti-tumour necrosis factor agents, such as infliximab, impaired the response to pneumococcal vaccination and therefore recommended vaccination prior to treatment (Fiorino et al, 2012). Although vaccine response may not be as effective during immunosuppression, there is evidence to show that vaccination prior to immunosuppression is beneficial; furthermore, vaccination during immunosuppression, if safe, may still support some immune response (Pittet and Posfay-Barbe, 2021). Serological testing may be used to monitor antibody levels, to determine the level of protection following certain vaccinations (Pittet and Posfay-Barbe, 2021).

Vaccination schedule for children and young people in England

The national vaccination schedule for children and young people (Table 1) is regularly updated and available via the UK Health Security Agency (UKHSA) on the Gov.uk website. The schedule lists routine immunisations and, as such, it does not include the current COVID-19 immunisation schedule, which at time of writing has included the rollout of vaccinations to the 5-11-year age group (NHS England, 2022).

Further immunisations may be required, but are given selectively based on the likelihood of infection or potential for increased severity of illness, such as BCG vaccination for protection against tuberculosis (TB) in infants who are born in areas of England with a high incidence of TB or hepatitis B vaccination for babies born to hepatitis B positive birthing mother. Influenza vaccination is also recommended for children aged 2-18 years however, this must be in context of the clinical risk for the child should they contract influenza as well as their immune status at the time.

For some children and young people their immune status is influenced by a primary or acquired immunodeficiency, immunosuppressive treatment or biological therapy, or if their birth mother was in receipt of an immunosuppressive therapy during pregnancy. Practitioners administering vaccinations need to be aware of this as part of effective medicines administration. In some cases, a prescriber may deem the risks of contracting the illness are outweighed by the risks posed by the vaccination. Live vaccination in some patients may lead to severe or fatal levels of infection and therefore this should be considered carefully by a specialist team (Peate and Dryden, 2022).

Types of vaccine and how they produce immunity

Different types of vaccine promote immunity by stimulating the immune response in different ways (Table 2). These are based mainly on either: whole pathogens (live-attenuated or inactivated), subunit, recombinant, polysaccharide, and conjugate vaccines, RNA or DNA (Centre for Clinical Vaccinology and Tropical Medicine, 2020).There are vaccines such as the COVID-19 vaccines that use either nucleic acid or viral vectors to produce immunity (Office of Infectious Diseases, 2021; National Institute for Health and Clinical Excellence (NICE), 2022). All vaccines should have their type listed within the manufacturer's patient information.

In the UK, there are several live-attenuated vaccines available and some are commonly used in the childhood vaccination programme (Public Health England (PHE), 2016). It is important to know which of these are live-attenuated vaccines because they may cause severe, life-threatening infection in immunosuppressed individuals; this is due to their ability to replicate rapidly in those whose immune system is not able to contain and neutralise or destroy the pathogen (NICE, 2022).

Some of the live-attenuated vaccines available in the UK are listed below, but always check the manufacturers information prior to administration:

• Live influenza vaccine
• Measles, mumps and rubella (MMR) vaccine
• Rotavirus vaccine
• Shingles vaccine
• BCG vaccine
• Oral typhoid vaccine
• Varicella vaccine
• Yellow fever vaccine.

Primary and secondary immunodeficiencies

Immunodeficiency results from a failure or absence of elements of the immune system, including lymphocytes, phagocytes and the complement system. Primary and secondary immunodeficiencies can have a range of causes and vary in severity.

The deficiencies may occur due to the pathophysiology of a genetic disorder or disease and in some cases can be compounded by treatment with immunosuppressive medications. There are over 300 primary immune deficiencies and they are generally caused by deficiencies in the function of B cells, T cells, complement cells, phagocytes, or a combination of these (British Society for Immunology, 2017). Secondary immunodeficiencies (or acquired immunodeficiencies) are more often caused by the environment, disease or medical treatment. The Green Book (UKHSA, 2022) discusses these in more detail. Some children and young people with these conditions may be able to have live vaccines if they are not immunosuppressed at the time. Some examples of primary and secondary immunodeficiencies are listed below. Please note that this list is by no means exhaustive (British Society for Immunology, 2017):

• Immunosuppression due to acute and chronic leukaemias (such as ALL, AML and LL) and lymphomas
• Severe immunosuppression due to HIV/AIDS
• Cellular immune deficiencies (eg severe combined immunodeficiency (SCID) or Wiskott-Aldrich syndrome)
• Following receipt of allogenic (cells from a donor) or autologous (patient's own) stem cell transplant in the past 24 months and demonstrating no ongoing immunosuppression or graft versus host disease (GVHD).

There are no exact statistics available for how many children and young people are living with immunodeficiencies in the UK. However, it is thought that around 5000 people are living with primary immunodeficiency (British Society for Immunology, 2017); around 1800 children and young people are diagnosed with cancers every year (Children with Cancer UK, 2021). For many children and young people with a primary immunodeficiency vaccination is very important, but where there are only live vaccinations they may have to rely on herd immunity within the population (British Society for Immunology, 2017).

Post-immunosuppression vaccination

It is important to identify the best timings to vaccinate those who are:

• Unvaccinated
• Have an incomplete vaccination history.
• Inactivated vaccines are safe to administer to immunocompromised patients; however, their response to the vaccine may be diminished or absent, and for some vaccinations an increase in dose or the number of doses may be indicated (PHE, 2020).

Patients who have received a bone marrow transplant are likely to have lost any protective antibodies acquired from exposure or vaccination prior to transplantation. It is not clear whether the recipient acquires donor immunity and therefore should be considered for a re-immunisation programme. Specialist advice may be required.

The timings of live vaccinations are more complex and dependant on the type of treatment received. The body's response to a vaccine is influenced both by the disease being treated and the specific drugs used to produce immunosuppression.

Without a positive antibody response, additional measures to protect may be necessary, for example, immunoglobulin therapy in the event of exposure or school exclusion if there is an outbreak of a disease.

Clinical considerations

Live-attenuated vaccines may cause adverse effects in immunocompromised patients, however practitioners should be aware of alternative forms of vaccination such as inactivated or subunit vaccines that may be available.

Vaccinating immunocompromised patients should be considered on an individual basis to ensure potential benefits and risks are assessed (both of having the vaccination and remaining at risk of contracting the disease).

Re-vaccination or boosters may be necessary following immunosuppressive treatment.

Conclusion

Although immunocompromised children are unlikely to have optimal immune responses to vaccines, they will benefit from immunisation. Vaccination of immunocompromised children is challenging both in regards to efficacy and safety. Vaccination of the immunocompromised child is important given the increased risk of disease and higher rates of morbidity and mortality from vaccine-preventable infections. These children may also have increased risk of exposure to pathogens because they must frequently enter medical environments. Inactivated vaccines can generally be used without risk, but the patients who are most at risk for infectious morbidity and mortality as a result of their severely immunosuppressed state are also those least likely to respond to vaccination. Live vaccines must be used with care because of the potential risk of vaccine-associated disease.

CPD reflective practice:

• Vaccination practice changes regularly, consider how your area keeps up to date with new clinical practice
• Are there any challenges to supporting immunocompromised patients in your clinical area?
• Immunisation is part of health promotion, how could health promotion be strengthened within your own practice and the practice for your area?

Key Points:

• Children and young people who are immunocompromised need to have their immunisations carefully considered by a specialist prior to administration
• Children and young people might be immunocompromised for a range of reasons, due to both physiological and treatment reasons
• Vaccinations are developing and new vaccinations have rigorous testing prior to use in children and young people
• Vaccinations have different mechanisms of action and create immunity in different ways