COVID-19 vaccines and PID

In response to the positive news about the development of COVID-19 vaccines, Dr Matthew Buckland, Chair of our Medical Advisory Panel, has issued the following statement on behalf of PID UK:

'The recent news concerning the RNA vaccines is highly encouraging and we look forward to the full results being published. Patients with primary antibody deficiency, including CVID and XLA, cannot produce reliable antibody responses, by definition. Those with combined immune deficiencies, including SCID, will not make good T cell responses to a vaccine. For these individuals a non-live vaccine is'safe' but will not offer protection against COVID. For patients with milder immunodeficiencies e.g. specific antibody deficiency, MBL deficiency, Selective IgA deficiency a normal vaccine response is likely. For PID patients a vaccine means the likely development of robust herd immunity, protecting them by reducing the amount of virus circulating in the community.  It will also mean reliable antibody levels in plasma donors, reflected in replacement IVIG/SCIG about 6 months or so after the vaccine is widely taken up.  As with the advice on seasonal flu vaccine, we encourage PID patients to have a safe vaccine, when available, since they may get some albeit minor benefit, and as a way of encouraging those around them to have it, where the highest benefit is likely to be derived.'

Frequently asked questions

Q. What are RNA vaccines and how are they different from 'conventional' vaccines?

A. RNA is an abbreviation for ribonucleic acid. mRNA acts as a messenger carrying instructions from DNA to make proteins.

Traditional virus vaccines use actual viruses that are weakened so they do not harm people and have to be grown in chicken eggs; a process that can take many months.  By contrast, the COVID-19 RNA vaccines delivers part of the virus genetic coding for the 'spike' protein. This RNA is then coated in a lipid so it can enter the body's cells and this is injected into the patient. The RNA vaccine then enters the cells and instructs them to produce the COVID spike protein. This prompts the immune system to produce antibodies and activate T cells to destroy infected cells.

RNA based vaccines are easier and faster to develop, once scientists have the genetic sequence of the protein they want to create.  Protein based vaccines are harder to manufacture but many successful vaccines have been produced in this way, e.g. Hepatitis B and some flu vaccines use this method.

Q. How much do we know about the vaccines recently in the news?

A. Pfizer/BioNtech and Moderna have recently announced highly successful interim results from their COVID-19 vaccines trials, and results from other vaccine trials are expected soon. 

Interim findings from Pfizer/BioNtech indicate their RNA vaccine is 90% effective in preventing COVID-19. Two doses are needed to give protection. The vaccine has been tested on 43,500 people in six countries and no safety concerns have been raised. However, the data presented is not the final analysis as it is based on only the first 94 volunteers to develop COVID so the precise effectiveness of the vaccine may change when the full results are analysed.

The Moderna trial involved 30,000 people in the US and the analysis was based on the first 95 to develop COVID-19 symptoms. Two doses are needed to give protection. Only five of the COVID cases were in people given the vaccine and 90 were in those given the placebo treatment. The company says the vaccine is protecting 94.5% of people. The data also shows there were 11 cases of severe COVID in the trial, but none happened in people who were immunised.  Again, these are interim results.

The Oxford University/AstraZeneca vaccine uses a modified, inactivated cold virus to carry the genetic information of COVID into the body to get the immune system to mount a response. Early data from the clinical trials suggests it is safe and could protect up to 70% of people. There is good data that it will work in elderly people.  The vaccine does not need to be shipped or stored in an ultra-cold environment, it is also considerably cheaper than the Pfizer/BioNtech and Moderna vaccines.

There are some unknowns about the vaccines, for example, we do not know if the vaccine stops you spreading the virus or just from developing symptoms; or if it works equally well in high-risk elderly people.  We also do not know how long the immunity will last and this question will only be answered by long-term follow up studies.

Q. Have any of the vaccine trials involved people with primary immunodeficiency? 

A. We do not know precisely the mix of people who have taken part in the clinical trials but PID patients would not be eligible to take part in a vaccine trial in the way that they are conventionally set up.  

Q. Is there any evidence about the effectiveness of the RNA vaccines for PID patients?

A. In short, no, because PID patients haven't been enrolled in the trials.  Our experience to date of patients with antibody deficiency and COVID-19 infection suggests that the antibody response is at least as important as T-cell responses for clearing this virus. The pre-clinical vaccine trial data suggests that antibody is essential for preventing primary infection. There will be more research data available about this over the coming months. The preliminary data indicates, therefore, some people with certain types of PID may not respond to the vaccination to get reliable protection.

Q. I have CVID, and since many other immunodeficient patients don't develop antibodies to vaccines and have poor T cell responses why are you encouraging people to have the vaccine when available?

A. Taking flu as an example, unfortunately we don't have routine antibody tests or T-cell function tests to see if patients have responded to vaccination given in the clinic and we suspect that many will not.  We do know the licenced vaccines are safe. We also know that those with poorer immunity such as the elderly can make a useful response. If patients might derive even a tiny amount of protection from a safe vaccine, many doctors think that is a worthwhile balance, given that influenza like COVID can result in deaths.  The exception to this is we do not recommend live vaccine in many children with more significant PID.

The PID community can do its bit to encourage friends and family to have an approved COVID vaccination. This will help protect those who don't have immunity to COVID-19 infection.

Q. What wider benefits will a COVID vaccination programme have for the primary immune deficiency communities?

A. Wider benefits include the likely development of robust herd immunity, protecting immunodeficiency patients by reducing the amount of virus circulating in the community.  It will also mean reliable antibody levels in plasma donors and this will be reflected in replacement IVIG/SCIG therapies after about 6 months or so after the vaccine is widely taken up. 

Q. How safe are the vaccines and who will monitor their safety?

A. All vaccines undergo extensive safety testing and must meet exacting standards to progress through the different stages of clinical trials. Their use must be approved and licensed before their use through expert review of all trial data through the Medicines and Healthcare products Regulatory Agency (MHRA). They check that the trial meets the necessary efficacy and safety levels. You can find out more about this process at http://vk.ovg.ox.ac.uk/vaccine-development

Q. When will we know if the vaccines are working for the general population?

A. The government is keeping tabs on infection by age and location.  We should start to see a fall in cases and hospitalisation in those groups targeted by the vaccine first within 2 months of the vaccination roll-out.

Q. How will the safety of the vaccines be monitored after the vaccination programmes start?

A. The safety of the vaccines will be monitored on an ongoing basis, as with all licensed drugs. This is undertaken by the Medicines and Healthcare products Regulatory Agency (MHRA) through the Yellow Card Scheme. Reports of suspected side effects are sent to the MHRA by drug companies (who are obliged to pass on any reports of suspected side effects that are defined as serious), health professionals, and patients themselves.

The data are evaluated each week, and the reported side effects are compared against the expected side effects as detailed in the information sheet for the vaccine. If a previously unidentified reaction emerges, or the frequency of reactions is not in line with what is expected, then the MHRA will investigate carefully. What happens next depends on the kind of side effect identified, but options include insisting that details of the new side effect are given in the product information leaflet or giving out warnings identifying groups of patients who should not be given the vaccine. In rare circumstances, the vaccine may be withdrawn from use.

Q. Will people with antibody deficiency get any direct benefit from having a vaccination?

A. This remains unclear and until we know most doctors are likely to give the same advice as flu-vaccine, if it gives even a tiny benefit from T-cell responses to reduce either the risk of infection or to make the illness less severe then as long as it has been licenced and is safe, then antibody deficient patients should consider having it.  We should also acknowledge that some people with e.g. specific antibody deficiency may make a good response to COVID vaccines, just as they might to tetanus but not to e.g. pneumococcus.

Q. Who decides on the priority list for a COVID vaccination programme?

A. The Joint Committee on Vaccination and Immunisation (JCVI) provides advice to the Government about this. They examine data on who suffers the worst outcomes from coronavirus and who is at highest risk of death.  More information can be found at https://www.gov.uk/government/publications/priority-groups-for-coronavirus-covid-19-vaccination-advice-from-the-jcvi-25-september-2020

Q. Who will be prioritised for the COVID vaccination programme?

A. Age is, by far, the biggest risk factor for COVID so older age groups will be targeted first.

The JCVI interim guidance says the order of priority would be as below but the final decision has yet to be taken:

  • All those aged 80 and over and health and social care workers
  • Anyone 75 and over
  • People aged 70 and over
  • All those aged 65 and over
  • High-risk adults under 65
  • Moderate-risk adults under 65
  • All those aged 60 and over
  • All those 55 and over
  • All those aged 50 and over
  • The rest of the population, with priority yet to be determined.

Q. When will the vaccines become widely available?

A. The vaccines need to authorised for use by the MHRA first and their decision will be based on the full data as to the safety and how well the vaccines work to protect against COVID.  The Government has yet to announce the start date of an immunisation programme but infrastructure and logistical plans are being drawn up.

Q. Will the vaccines stop the spread of COVID?

A. It is unlikely that a vaccination programme will be able to fully stop the spread of the COVID virus unless we see high level uptake of a highly effective vaccine. The disease may well become endemic in the global population like flu and have to be managed on a yearly basis through vaccination programmes.  This means that everyone, and most importantly those clinically vulnerable should continue to take measures to protect themselves from catching the virus.

Q. Why are so many different types of vaccines being developed?

A. Given the scale and importance of the challenge of developing a COVID vaccine and the need for vaccination programmes to be available globally, different strategies and approaches are being used in the hope that some of these avenues of research and development will pay off. The pace of the research is unprecedented.  

Q. How can I find out more about the development of COVID vaccines and vaccination programmes?

A. These websites may be helpful:

Reviewed by the Chair of the PID UK Medical Advisory Panel 18th November 2020 and updated 24th November 2020.