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expert reaction to preprint looking at immune responses to the COVID-19 vaccine in people with impaired immune systems

A preprint, an unpublished non-peer reviewed study, from the OCTAVE trial, examines the immune response to COVID-19 vaccination in patients with conditions potentially leading to diminished immune response capacity.

This Roundup accompanied an SMC Briefing.


Dr Beth Psaila, Cancer Research UK Advanced Clinician Scientist and Group Leader at the MRC Weatherall Institute of Molecular Medicine and Honorary Consultant in Haematology, University of Oxford, said:

“The original studies that confirmed the effectiveness of COVID-19 vaccines were performed in healthy volunteers. Patients with certain health conditions may have a poorly-functioning immune system – either because of their medical condition, or because of treatments they are taking. Therefore, studying responses to COVID-19 vaccination in patients who may have an impaired immune system is critically important as we move to the next phase of this pandemic.

“This report focuses on 600 patients with chronic diseases, and provides important insights into overall responses to COVID-19 vaccination in patients with chronic infection, and which groups of patients might be most vulnerable.

“Overall, the data is very reassuring. Almost 90% of patients overall had a detectable antibody response to the vaccine after 2 doses, and T cell responses were equally as strong in the patients as seen in healthy controls.

“However, antibody responses were not detectable in 1 in 10 patients, and the overall levels of antibody were lower than in a control group of healthy individuals. Further study is now needed to test whether patients without detectable antibody responses after 2 doses of vaccine may respond to booster doses, and more importantly, whether this lower antibody level will translate to a higher likelihood of infection or more severe infections. What is particularly interesting is that the responses to vaccination were more robust in patients who had previously had COVID-19 infection, suggesting that capacity for immunity to develop does exist, and suggesting that improved responses may be achieved by booster doses.

“I look forward to reading further updates from the OCTAVE study and similar work ongoing, which is so critical to help shape our response to this evolving pandemic.”


Prof Eleanor Riley, Professor of Immunology and Infectious Disease, University of Edinburgh, said:

“This study provides unsurprising but nevertheless very important information.

“We had always expected that people with certain specific underlying health conditions might respond sub-optimally to COVID-19 vaccination. People who are on treatments specifically designed to suppress their immune system are of particular concern. These individuals will have been advised that they are susceptible to infection and may respond poorly to vaccination. The vast majority of them will have been advised to shield during the height of the pandemic.

“It is not surprising, therefore, to find that many of these “at risk” groups have lower antibody responses after two doses of the vaccine than might otherwise have been expected.

“However, it isn’t all bad news.

“Firstly, many of these patients did make a detectable antibody response and their response went up again after the second dose of vaccine. It is quite possible that they will make an even better response after a third dose of vaccine. These data therefore offer support for the notion that people with specific co-morbidities should be prioritised for a “booster” dose of vaccine  in the next few weeks.

“Secondly, the study identifies which of the several potentially vulnerable groups we should actually worry about. On the whole, and as predicted, people who are taking drugs to suppress their B cells (which are the cells that make the antibodies) responded least well. However, some other potentially “at risk” groups actually responded quite well, meaning they are not as “at risk” as we might have feared. This information will be very useful to clinicians in advising their patients.

“Finally, in almost all cases,  T cell responses were as good as those seen in healthy people. As it is T cells that are particularly effective at stopping us getting severely ill and needing hospital treatment, we would expect that the vaccine is still offering substantial protection to most of these highly vulnerable people.

“Data on infection and hospitalisation after vaccination should emerge soon and will give us a better idea of how effective the vaccines are in real life in these highly vulnerable patients.” 


Professor Charles Swanton, Cancer Research UK’s chief clinician, said:

“This latest study broadly reflects the evidence we’ve seen so far and includes only a small number of cancer patients, with a limited number of cancer types. So it’s not clear if these results can be generalised or the level of protection given by the antibody response. Questions remain around whether a booster would provide more protection. Overall, the majority of cancer patients had an immune response to the vaccine, even if levels of antibodies were lower in some cases than healthy controls, but the study didn’t look at how this response translates to COVID-19 protection. We urgently need data across blood and solid tumour cancer types to understand which groups are most at risk from vaccine breakthrough infections.

“We know the results could be worrying for those who are clinically vulnerable, but anyone undergoing cancer treatment should continue to follow the advice of their doctors and we encourage all who can to get the vaccine. With restrictions easing, you may wonder if you should be shielding – talk to your doctor, family and friends and ultimately you need to do what’s right for you.”


Prof Neil Mabbott, Personal Chair in Immunopathology, University of Edinburgh, said:

“This study of the immune responses to COVID-19 vaccination in a large cohort of immunocompromised patients provides important information on how strongly their immune systems are responding to these vaccines.  As we feared, this study shows that approximately 40% of these patients with weakened immune systems mount much lower, if any, antibody responses to the vaccine.  However, there is a positive note in this study in that many of these patients were able to make some responses suggesting they may have partial protection.  There is much debate in the UK about whether we should be rolling out booster jabs to adults who have already received two doses.  Of course, we don’t currently have a reliable serum marker that can tell us whether and how well an individual is protected from developing serious COVD-19 disease after vaccination.  Despite this, the results in this study provide useful evidence to inform these decisions.  This study supports the suggestion that if booster jabs are to be used, they should be prioritised to those such as individuals in this study, who have weakened immune responses and responded poorly to their previous vaccinations.”


Dr Doug Brown, Chief Executive of the British Society for Immunology, said:

“People with immune systems that function sub-optimally, either due to a medical condition or due to medication they take, are amongst the most vulnerable to getting very sick from catching SARS-CoV-2, making providing them with protection against the virus a priority.

“This new paper from the OCTAVE team is one of the most comprehensive studies to date of the immune responses generated by COVID-19 vaccination in patients with impaired immune systems. They found a great deal of variation in the immune responses produced by patients with different conditions following COVID vaccination. This is to be expected – the immune system is extremely complex and conditions will differ in how they affect the functioning of the immune system.  The good news is that approximately 60% of patients produced an immune response similar to those seen in healthy people after two doses. While patients with some conditions such as ANCA-Associated Vasculitis or inflammatory arthritis were more likely to produce significantly lower antibody levels following vaccination, T cell responses seemed to hold up much better.

“We still do not yet fully understand what components and levels of immune response are important in generating immunity following COVID-19 vaccination, what immunologists term the ‘correlates of protection’. It is therefore not yet possible to know whether these reduced immune responses result in less immunity for these patients – this is the subject of ongoing studies.  We still recommend that all people with impaired immune systems get two doses of the COVID vaccine as it will offer them the best chance of protection against falling sick with COVID-19.

“As we find our way out of the pandemic, we must keep researching how to optimise COVID vaccination schedules for patients with impaired immune systems to maximise future protection for these people. This includes examining whether booster doses would be useful and looking into other therapeutic options for the small minority of patients who are unable to generate an immune response following vaccination. ”



The preprint ‘Examining the immunological effects of COVID-19 vaccination in patients with conditions potentially leading to diminished immune response capacity – the OCTAVE Trial’ was uploaded to the Preprints with The Lancet site at 17:00 UK time Tuesday 24 August.



All our previous output on this subject can be seen at this weblink:



Declared interests

Prof Eleanor Riley: “No conflicts to declare.”

Prof Neil Mabbott: “I have no conflict of interest.”

Dr Doug Brown: “Trustee of the Association of Medical Research Charities.” 

None others received.

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