Public Health England News and Media

01 Sep 2021

JCVI issues advice on third dose COVID-19 vaccination for severely immunosuppressed

The Joint Committee on Vaccination and Immunisation (JCVI) is advising that people with severely weakened immune systems should have a third vaccine dose as part of their primary COVID-19 vaccination schedule.

This third dose should be offered to people over 12 who were severely immunosuppressed at the time of their first or second dose, including those with leukaemia, advanced HIV and recent organ transplants. These people may not mount a full response to vaccination and therefore may be less protected than the wider population.

This offer is separate to any potential booster programme. The JCVI is still deliberating the potential benefits of booster vaccines for the rest of the population and is awaiting further evidence to inform this decision.

Immunosuppression varies widely in severity and duration. Many people who are immunosuppressed have lower levels of antibodies after COVID-19 vaccination, as some studies have shown.

Preliminary data from the OCTAVE trial showed that almost everyone who was immunosuppressed mounted an immune response after 2 doses, as indicated by either antibodies or T cells. However, in around 40% of people, the levels of antibodies were low. It is not clear how much this may affect protection against COVID-19 as antibodies represent only part of a person’s immune response.

People with severe immunosuppression are more likely to be severely ill if they do catch COVID-19.

Studies are ongoing to see how effective a third dose is for immunosuppressed people, but it is very unlikely to cause any harm. Therefore, on balance, the JCVI’s view is that a third dose can be safely offered as it may increase their protection.

Professor Wei Shen Lim, Chair of COVID-19 Immunisation for the JCVI, said:

“We want people with severely suppressed immune systems to have the best chance of gaining protection from COVID-19 via vaccination. Therefore, we are advising they have a third vaccine dose on top of their initial 2 doses, as we hope this will reduce their risk of severe outcomes such as hospitalisation and death.”

The JCVI advises that for adults aged 18 and older, either the Moderna or Pfizer-BioNTech COVID-19 vaccines be administered for the third dose, as a number of studies have reported an increased immune response in some immunosuppressed people after a third dose of an mRNA vaccine. For those aged 12 to 17, the Pfizer-BioNTech vaccine is preferred.

The decision on the timing of the third dose should be made by their specialist. As a general guide, the third dose should usually be at least 8 weeks after the second dose but with flexibility to adjust the timing so that, where possible, immunosuppression is at a minimum when the vaccine dose is given.

This will enable a better immune response to be generated. For example, it is preferable to give a vaccine dose before someone undergoes chemotherapy, rather than during their treatment.

Those with less serious immunosuppression are not included in this advice but are likely to become eligible for another dose as part of a potential booster programme, pending further advice from the JCVI.

In the event of a booster programme, it is expected that severely immunosuppressed people will also be offered a booster dose, at a suitable interval after their third dose.

A third primary dose is an extra ‘top-up’ dose for those who may not have generated a full immune response to the first 2 doses. In contrast, a booster dose is a later dose to extend the duration of protection from the primary course of vaccinations.

Contact Information

Anthony White
anthony.white@phe.gov.uk

Notes to editors

Notes to editors:

Severe immunosuppression at the time of vaccination is defined using the guidance and timings stated below:

  1. Individuals with primary or acquired immunodeficiency states at the time of vaccination due to conditions including:
  • acute and chronic leukaemias, and clinically aggressive lymphomas (including Hodgkin’s lymphoma) who were under treatment or within 12 months of achieving cure
  • individuals under follow up for a chronic lymphoproliferative disorders including haematological malignancies such as indolent lymphoma, chronic lymphoid leukaemia, myeloma, Waldenstrom’s macroglobulinemia and other plasma cell dyscrasias (Note: this list is not exhaustive)
  • immunosuppression due to HIV/AIDS with a current CD4 count of <200 cells/µl for adults Primary or acquired cellular and combined immune deficiencies – those with lymphopaenia (<1,000 lymphocytes/ul) or with a functional lymphocyte disorder.
  • those who had received an allogeneic (cells from a donor) or an autologous (using their own cells) stem cell transplant in the previous 24 months
  • those who had received a stem cell transplant more than 24 months ago but had ongoing immunosuppression or graft versus host disease (GVHD)
  • persistent agammaglobulinaemia (IgG < 3g/L) due to primary immunodeficiency (e.g. common variable immunodeficiency) or secondary to disease / therapy
  1. Individuals on immunosuppressive or immunomodulating therapy at the time of vaccination including:
  • those who were receiving or had received immunosuppressive therapy for a solid organ transplant in the previous 6 months.
  • those who were receiving or had received in the previous 3 months targeted therapy for autoimmune disease, such as JAK inhibitors or biologic immune modulators including B-cell targeted therapies (including rituximab but in this case the recipient would be considered immunosuppressed for a 6 month period), T-cell co-stimulation modulators, monoclonal tumour necrosis factor inhibitors (TNFi), soluble TNF receptors, interleukin (IL)-6 receptor inhibitors., IL-17 inhibitors, IL 12/23 inhibitors, IL 23 inhibitors. (N.B: this list is not exhaustive)
  • those who were receiving or had received in the previous 6 months immunosuppressive chemotherapy or radiotherapy for any indication.
  1. Individuals with chronic immune-mediated inflammatory disease who were receiving or had received immunosuppressive therapy prior to vaccination including:
  • high dose corticosteroids (equivalent ≥ 20mg prednisolone per day) for more than 10 days in the previous month
  • long term moderate dose corticosteroids (equivalent to ≥10mg prednisolone per day for more than 4 weeks) in the previous 3 months
  • non-biological oral immune modulating drugs e.g. methotrexate >20mg per week (oral and subcutaneous), azathioprine >3.0mg/kg/day; 6-mercaptopurine >1.5mg/kg/day, mycophenolate >1g/day) in the previous 3 months
  • certain combination therapies at individual doses lower than above, including those on ≥5mg prednisolone per day in combination with other immunosuppressants (other than hydroxychloroquine or sulfasalazine) and those receiving methotrexate (any dose) with leflunomide in the previous 3 months
  1. Individuals who had received high dose steroids (equivalent to >40mg prednisolone per day for more than a week) for any reason in the month before vaccination

Individuals who had received brief immunosuppression (≤40mg prednisolone per day) for an acute episode (e.g. asthma / COPD / COVID-19) and individuals on replacement corticosteroids for adrenal insufficiency are not considered severely immunosuppressed sufficient to have prevented response to the primary vaccination.