This is very welcome guidance and is based on a considerable body of evidence that many people with immunosuppressive diseases or who are receiving immunosuppressive treatments make a detectable but suboptimal antibody response after two doses of the vaccine.

There is every reason to expect that their immunity can be substantially improved by giving them a third dose.

It would be wise to actively monitor the response to vaccination in this group of patients so that they can be advised individually of their immune status and adjust their daily activities accordingly.

The decision to give a third dose of vaccine to those who are likely to have responded poorly to the first two doses is to be welcomed.  However, I find it very worrying to see reports that pressure is being put on JCVI (Joint Committee on Vaccination and Immunisation) to decide that boosters should be given to a high proportion of adults and to young people aged 12-15 years, even if they have no underlying health problems.

We should be using the vaccine, a precious resource, carefully and any action should be based on the evidence.  The JCVI is the expert body that can weigh all the evidence and come to a considered decision based on the balance of risks and benefits.  It should not, and will not, be forced into an inappropriate decision by pressure from politicians or the media.  The latter would be the first to complain if someone who had little to gain from having the vaccine came to harm.

Is this sensible, evidence-based advice?

“It is good to see this advice from the JCVI offering a third vaccination shot to patients with certain immune disorders.  We have known for some time that this group respond less well to vaccination than fully immune competent individuals, and recent publications have shown that adding a third dose to the primary dose schedule can increase response in this group.  The committee have provided the relevant arguments for the proposed approach within the document, facilitating the proposed dose scheduling for individuals undergoing primary vaccination courses as well as comment concerning the need for additional booster vaccinations likely at six monthly intervals in future.

What evidence is it based on?

“The JCVI have provided the relevant reference documentation containing the information on which their advice is based.  This includes the observed reduction in neutralizing antibody titres following 2 vaccination doses in immune suppressed individuals, as well as the results of studies investigating a third dose (using an mRNA vaccine) in this population.  It is acknowledged that there are no current established immune correlates of protection, but given the low response to dual vaccination in this group and the increased response found in many subjects following a third dose, it is sensible to extrapolate this information and recommend adjustment of the vaccination schedule for immunesuppressed individuals.

Why is it the Pfizer and Moderna vaccines being recommended for these third doses; is that evidence-based?

“The committee state that the reason for this advice is observed higher antibody responses noted following mRNA vaccines compared to the ChAdOx01 vaccine and the safety and response data which has been generated for the third dose approach using mRNA vaccine which is not available for the ChAdOx01 vaccine at this time.  However, by extrapolation, it would be anticipated that a third dose of the ChAdOx01 vaccine should behave similarly, and therefore the committee also advise that if a third dose with ChAdOx01 would facilitate administration of a third dose in this vulnerable population, then the ChAdOx01 vaccine can also be used.  It is noted that the Com-Cov study has suggested that heterologous vaccination (i.e. using different vaccine types) can also result in higher levels of immune response although this has not been explored in immune suppressed subjects but again, by extrapolation, one might anticipate a similar impact.  Hence doctors might choose to use a heterologous vaccine if appropriate for their patients.

Any other comments about this advice?

“There remain some immunesuppressed subjects that may not respond completely to vaccination regardless of number of doses administered: the MHRA has recently approved Ronapreve, a monoclonal antibody combination, which could offer additional protection to severely immune suppressed individuals in close contact with infected persons.  In addition, results from prophylaxis studies with AZD7442 (a monoclonal antibody combo) suggest potential for long acting protection against COVID following a single administration which might last for up to one year (https://www.astrazeneca.com/media-centre/press-releases/2021/azd7442-prophylaxis-trial-met-primary-endpoint.html).  These are passive immunisation approaches which one might have expected to have been considered alongside active immunisation approaches given the nature of the patient group for whom this advice is provided today.  Perhaps we might anticipate additional advice for this group as and when supply of these agents is secured for use in the UK.