21st February 2024

Vaccines and Immunoglobulins in Practice

Types of vaccines

Overview

It is important to be aware of the common types of vaccines along with specific situations where certain vaccines should not be given. 

Vaccines stimulate the immune system to recognise pathogens and produce antibodies against the pathogen. There are several types of vaccines used in current clinical practice:

• Live attenuated vaccine – Weakened ( attenuated) whole bacteria/virus by modifying the pathogen’s genetic material. This appears to elicit the best immune response but may result in uncontrolled pathogen replication in patients with weakened immune systems. Examples include:
  • Rotavirus 
  • Varicella/shingles
  • BCG
  • Yellow fever
  • ORAL typhoid
  • Live influenza
  • MMR
• Inactivated vaccine – Whole pathogens that have been killed or modified so that they are incapable of replicating. Examples include:
  • Inactivated polio
  • Hepatitis A
  • Rabies 
  • Japanese encephalitis
  • Inactivated influenzae 
• Recombinant protein vaccine – Protein subunits are created by inserting pathogenic DNA into yeast cells to produce polysaccharides/proteins that induce an immune response. Examples include:
  • Hepatitis B
  • Human papilloma virus
  • Meningococcal B
• Toxoid vaccine – Inactivated toxins are produced to induce immunity without causing clinical symptoms due to the inactivated nature of the toxoid. Examples include:
  • Diphtheria
  • Tetanus
  • Pertussis
• Conjugate vaccine – The pathogen’s polysaccharide antigen is attached to another material to induce a more robust immune response against the polysaccharide antigen. Examples include: 
  • Haemophilus influenzae B 
  • Meningococcal A,C,W,Y
  • Pneumococcal

Special considerations

Vaccines have very few absolute contraindications and have few side effects. The most common absolute contraindication to vaccines includes:

• Confirmed anaphylactic reaction to previous vaccine dose
• Confirmed anaphylactic reaction to a component within the vaccine

Special considerations should be undertaken with the following patient populations:

• Egg/Latex allergy
• Primary/acquired immunodeficiency
  • This includes acute/chronic lymphoma and leukaemia; HIV/AIDS; cellular immunodeficiency due to SCID; Wiskott-Aldrich syndrome; DiGeorge syndrome; and recent stem cell transplant within the past 24 months. 
• Immunosuppressive therapies, including biological therapies
  • This includes chemotherapy, radiotherapy, high-dose corticosteroids, immunosuppression for solid organ transplants, and higher doses of methotrexate and azathioprine.
  • Low-dose corticosteroids and lower doses of non-biologic immune-modulating medications are not sufficient immunosuppression to withhold live vaccines. 
• Pregnancy

Patients with the above special consideration should not receive live, attenuated vaccines. Before administration, the relevant speciality prescribing the immunosuppressive therapy should be consulted. In pregnancy, live vaccinations should not be given due to the theoretical risk of foetal infection. Other vaccine types are safe to be administered to all these patient groups. 

References

• Vaccine Knowledge Project. (2021). Types of Vaccine. Accessed on 2022 Mar 28. Available from: https://vk.ovg.ox.ac.uk/vk/types-of-vaccine.
• UK Health Security Agency, & Department of Health & Social Care. (2020). Contraindications and special consideration. Accessed on 2022 Mar 28. Available from: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/655225/Greenbook_chapter_6.pdf. 
• UK Health Security Agency, & Department of Health & Social Care. (2020). Immunity and how vaccines work. Accessed on 2022 Mar 28. Available from: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/949797/Greenbook_chapter_1_Jan21.pdf. 

Tetanus exposure

Treatment

Tetanus is an acute condition caused by Clostridium tetani through its tetanus toxin. The bacterium infiltrates the patient via its spores, which are ubiquitous in the soil and manure. Spores will enter the patient via an open wound or cut and will grow over a mean period of 10 days. Release of the tetanus toxin results in its classic symptoms of rigidity and skeletal muscle spasms. This can result in lockjaw and respiratory failure. 

Most patients should be fully vaccinated against tetanus as it forms part of the national immunisation schedule for children in the UK. Primary immunisation is done at ages 2, 3 and 4 months old. Booster immunisation is provided at three years post-primary immunisation and ten years post-1st booster. This should be sufficient to provide long-term immunisation against the tetanus toxoid. 

When faced with a wound, it is essential to determine if this is a tetanus-prone wound and the status of the patient’s tetanus immunisation. A tetanus-prone wound includes the following characteristics:

• Wounds that require surgical intervention that is delayed for > 6 hours,
• Puncture-type injury in an environment that likely resulted in contamination of material that likely contains tetanus spores ( soil/manure),
• Wounds containing foreign bodies,
• Compound fracture,
• Wounds resulting in systemic sepsis.  

High-risk tetanus-prone wounds are classified as any of the above, along with the following:

• Heavy contamination of materials, including soil/manure
• Wounds/burns with significant devitalised tissue
• Wound/burns requiring surgical intervention that has been delayed for over 6 hours. 

The treatment of choice for tetanus exposure involves tetanus immunoglobulin and tetanus vaccination. The need to administer the vaccine and tetanus immunoglobulin varies depending on the immunisation status and the tetanus-prone risk of the wound. The summary of treatment is as below and is adapted from the Green Book:

*A clean wound is < 6 hours old, with minor tissue damage, and non-penetrating. 

References

• UK Health Security Agency, & Department of Health & Social Care. (2020). Tetanus. Accessed on 2022 Mar 28. Available from: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/859519/Greenbook_chapter_30_Tetanus_January_2020.pdf. 
• Hibberd, P. (2021). Tetanus-diphtheria toxoid vaccination in adults. Accessed on 2022 Mar 28. Available from: https://www.uptodate.com/contents/tetanus-diphtheria-toxoid-vaccination-in-adults#H7. 
• National Institute for Health and Care Excellence clinical Knowledge Summary. (2021). Scenario: Laceration – High infection risk. Accessed on 2022 Mar 28. Available from: https://cks.nice.org.uk/topics/lacerations/management/laceration-high-infection-risk/. 

Varicella exposure

Treatment

Varicella is a highly infectious disease notifiable in Scotland and Northern Ireland. The condition usually begins with fever and malaise that lasts approximately 1-2 days before the onset of vesicles along the face, trunk, abdomen and limbs in order of progression. This will last for approximately 3-4 days before scabbing over. The virus may actively spread through the droplets or via contact with vesicular fluid until the vesicles dry up. Shingles can also result in varicella spread, as the reactivation of the varicella virus causes it. Chickenpox typically affects children, and the condition often runs a mild course, with shingles more prevalent in the elderly and immunocompromised population. 

Adults can also develop chickenpox if they have not been affected by this during their childhood. Adults and pregnant women are at higher risk when they have developed varicella infection due to the risk of fulminating varicella pneumonia and foetal varicella infection, respectively. Foetal varicella infection can result in foetal varicella syndrome, characterised by limb hypoplasia, microcephaly, cataracts, growth restriction, chorioretinal damage, and sudden foetal demise. 

The disease is usually self-limiting for most patients, and most patients will require supportive care and aciclovir. Varicella immunoglobulins (VZIG) are available to help reduce the likelihood of a high-risk patient developing severe varicella infection. The patient needs to fulfil the following criteria to be eligible for VZIG: 

• Significant exposure towards varicella
  • Disseminated zoster
  • Immunocompetent individuals with exposed lesions
  • Immunosuppressed individuals with localised lesions on any part of the body. 
• Timing of exposure to rash onset
  • Exposure to the patient 48 hours prior to the rash onset until the crusting of lesions for disseminated zoster OR from the day of onset of rash until crusting of lesions for localised zoster. 
• Closeness of contact – Does not apply to neonatal/maternal exposure
  • Contact in the same room (house/classroom/ward) for > 15  minutes.
  • Face-to-face conversation

The patient’s varicella antibody status also should be known, and the advice given will depend on the patient population. Below is the summary of the advice given by the Green Book:

*Immunocompromised is defined as patients with severe primary immunodeficiency; ongoing immunosuppressive treatment with chemotherapy, radiotherapy, biologics, corticosteroids and non-steroids immunosuppressive agents; HIV and stem cell transplant recipients. 

Varicella immunisation should not be given during the acute event, and the vaccine is contraindicated in both situations. Varicella vaccination can be considered in pregnant women once they have given birth. 

References

• UK Health Security Agency, & Department of Health & Social Care. (2020). Varicella. Accessed on 2022 Mar 28. Available from: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1056198/Green_Book_Chapter_34_v3_0.pdf. 
• Royal College of Obstetricians and Gynaecologists. (2015). Chickenpox in Pregnancy. Accessed on 2022 Mar 28. Available from: https://www.rcog.org.uk/media/y3ajgkda/gtg13.pdf. 
• National Institute for Health and Care Excellence Clinical Knowledge Summary. (2022). Scenario: Person exposed to chickenpox. Accessed on 2022 Mar 28. Available from: https://cks.nice.org.uk/topics/chickenpox/management/exposure-to-chickenpox/.