immunosuppression and vaccination

Last edited 04/2019

Live vaccines can, in some situations, cause severe or fatal infections in immunosuppressed individuals due to extensive replication of the vaccine strain

• for this reason, individuals with some types of severe primary or acquired immunodeficiency (see list below) should not be given live vaccines, and vaccination in immunosuppressed individuals should only be conducted in consultation with an appropriate specialist
• inactivated vaccines cannot replicate and so may be administered to immunosuppressed individuals, although they may elicit a lower response than in immunocompetent individuals

Live vaccines currently available in the UK are:

• live influenza vaccine (Fluenz Tetra)
• Measles, Mumps and Rubella vaccine (Priorix, MMRVaxPro
• Rotavirus vaccine (Rotarix)*
• Shingles vaccine (Zostavax)
• BCG vaccine
• Oral typhoid vaccine (Ty21a)
• Varicella vaccine (Varilrix, Varilvax)
• Yellow Fever vaccine

*Although the vaccine is a live attenuated virus, with the exception of severe combined immune-deficiency (SCID), the benefit from vaccination may exceed any risk in other forms of immunodeficiency

Most live vaccines should not be administered to individuals with primary or acquired immunodeficiency. This includes

• immunosuppression due to acute and chronic leukaemias and lymphoma (including Hodgkin's lymphoma)
• severe Immunosuppression due to HIV/AIDS (for BCG, the vaccine is contraindicated in all HIV positive individuals)
• cellular immune deficiencies (e.g. Severe combined immunodeficiency, Wiskott-Aldrich syndrome, 22q11 deficiency/DiGeorge syndrome**
• being under follow up for a chronic lymphoproliferative disorder including haematological malignancies such as indolent lymphoma, chronic lymphoid leukaemia, myeloma and other plasma cell dyscrasias (this is not an exhaustive list)
• having received an allogenic (cells from a donor) stem cell transplant in the past 24 months and only then if they are demonstrated not to have on-going immunosuppression or graft versus host disease (GVHD)
• having received an autologous (using their own stem cells) haematopoietic stem cell transplant in the past 24 months and only then if they are in remission

** Most patients with 22q11 deletion syndromes are able to receive live vaccines safely provided that they have no evidence of being severely immunocompromised. Specialist advice should always be sought to rule out severe immunosuppression

Antibody deficiencies affecting IgG or IgA antibodies are not of themselves a contraindication to live vaccination unless associated with T cell deficiencies.

If there is any doubt, immunological advice should be sought prior to administration.

Immunosuppressive therapy (including biologics)

Individuals who are on or have recently received high doses of certain immunosuppressive or biological therapies (see list below) should not be given live vaccines because of the risk of severe or fatal infections

• for those on lower doses of such therapies or those who completed therapy less recently live vaccination may go ahead after careful consideration - it may be possible for some immunosuppressed individuals to receive some vaccines. Vaccination of immunosuppressed individuals should only be conducted in consultation with an appropriate specialist

Live vaccines should not be administered to individuals on immunosuppressive therapy including:

• those who are receiving, or have received in the past 6 months, immunosuppressive chemotherapy or radiotherapy for malignant disease or non-malignant disorders
• those who are receiving, or have received in the past 6 months, immunosuppressive therapy for a solid organ transplant (with exceptions, depending upon the type of transplant and the immune status of the patient)
• those who are receiving or have received in the past 12 months immunosuppressive biological therapy (e.g. anti-TNF therapy such as alemtuzumab, ofatumumab and rituximab) unless otherwise directed by a specialist
• those who are receiving or have received in the past 3 months immunosuppressive therapy including:
  • adults and children on high-dose corticosteroids (>40mg prednisolone per day or 2mg/ kg/day in children under 20kg) for more than 1 week
  • adults and children on lower dose corticosteroids (>20mg prednisolone per day or 1mg/kg/day in children under 20kg) for more than 14 days
  • adults on non-biological oral immune modulating drugs e.g. methotrexate >25mg per week, azathioprine >3.0mg/kg/day or 6-mercaptopurine >1.5mg/kg/day
  • for children on non-biological oral immune modulating drugs (except those on low doses, see below), specialist advice should be sought prior to vaccination

Notes:

• ideally individuals who have received a live vaccine should wait until their immune response has been established to receive immunosuppressive therapy
• for most viral live vaccines a period of up to four weeks should be a sufficient - however, as the vaccine viruses are generally attenuated, immunosuppressive treatment should not be delayed if this could result in worsening of the underlying condition
  • in such situations, additional measures such as antibody-testing, monitoring for evidence of infection, the administration of antivirals or immunoglobulin may be considered
  • specialist advice should be sought on a case-per-case basis
• immunisation with live vaccines should be delayed until 6 months of age in children born to mothers who received immunosuppressive biological therapy during pregnancy
  • means that children born to mothers who were on immunosuppressive biological therapy during pregnancy will not be eligible to receive rotavirus vaccine (and will need to defer BCG, if indicated, for 6 months)
• many adults with chronic inflammatory diseases (e.g. rheumatoid arthritis, inflammatory bowel disease, psoriasis, glomerulonephritis) will be on stable long term low dose corticosteroid therapy (defined as up to 20mg prednisolone per day for more than 14 days in adult or 1mg/kg/day in children under 20kg) either alone or in combination with other immunosuppressive drugs
  • long term stable low dose corticosteroid therapy,either alone or in combination with low dose non-biological oral immune modulating drugs (e.g. methotrexate 25mg per week in adults or up to 15mg/m2 in children, azathioprine 3.0mg/ kg/day or 6-mercaptopurine 1.5mg/kg/day), are not considered sufficiently immunosuppressive and these patients can receive live vaccines

If there is any doubt, immunological advice should be sought prior to administration.

For further details consult the uptodate version of The Green Book - Chapter 6.

Reference:

• Immunisation Against Infectious Disease, HMSO, 1996
• PHE. Contraindications and special considerations: the green book, chapter 6 (October 2017)
• The Green Book - Chapter 6 - Contraindications and special considerations (April 2019).