Nearly 90% of immunocompromised patients generate some antibody response after two coronavirus jabs

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Vaccination of senior person in hospital
An effective vaccination programme has long been hailed as a route out of the pandemic. (Stock, Getty Images)

Nearly nine in 10 (89%) people with a compromised immune system generate some degree of an antibody response after receiving two coronavirus vaccine doses, research suggests.

The UK has four jabs in its immunisation arsenal against the pandemic – Pfizer-BioNTech, University of Oxford-AstraZeneca, Moderna and Janssen. These were approved after studies demonstrated they are up to 95% effective at warding off severe coronavirus complications in healthy adults.

To better understand the jabs' effectiveness in immunocompromised patients, scientists from across the UK analysed the blood samples of 600 people with conditions like cancer, arthritis and inflammatory bowel disease.

Early results of the ongoing study – published on The Lancet pre-print site – reveal that among those who did produce immune-fighting antibodies, two in five (40%) had lower levels than healthy individuals after two vaccine doses.

At four weeks after the second dose, 11% of the patients had failed to produce any antibodies.

Read more: AstraZeneca coronavirus jab causes clot in one in 50,000 under-50s

While the results will no doubt "be of concern" among immunocompromised patients, "the functional significance" of the findings when it comes to coronavirus protection is unknown.

Antibodies aside, nearly all of the patients generated a similar T cell response to healthy individuals. Another aspect of the immune system, T cells help to stimulate antibody production or directly destroy body cells that have already been infected by a virus.

Illustration of antibodies (y-shaped) responding to an infection with the new coronavirus SARS-CoV-2. The virus emerged in Wuhan, China, in December 2019, and causes a mild respiratory illness (covid-19) that can develop into pneumonia and be fatal in some cases. The coronaviruses take their name from their crown (corona) of surface proteins, which are used to attach and penetrate their host cells. Once inside the cells, the particles use the cells' machinery to make more copies of the virus. Antibodies bind to specific antigens, for instance viral proteins, marking them for destruction by other immune cells, such as the macrophage white blood cell behind the virus.
Antibodies are specific to each pathogen and lock onto their surface, neutralising or 'marking' it for destruction by other immune cells. (Stock, Getty Images)

"A significant number of people in the UK were advised to shield because they have conditions or long term illnesses which place them at greater risk of severe illness and death from COVID-19 [the disease caused by the coronavirus]," said study author Professor Pam Kearns, from the University of Birmingham.

"The rapid development of vaccines for COVID-19 has been a major step forward in the battle against this global pandemic and the most clinically-at-risk people were among the first in the UK to be offered one.

"While we know COVID-19 vaccines are highly effective in healthy individuals, questions have remained as to how effective they are in protecting the chronically ill.

Read more: Man dies from blood clot after Moderna jab

"These preliminary results and the results of our continuing and forthcoming research will be instrumental in helping inform how best to vaccinate patients with chronic conditions and protect them from COVID-19 infection in the future."

The Joint Committee on Vaccination and Immunisation (JCVI) has reportedly seen the preliminary data. The ongoing study, called Octave, is one of several trials that will inform the committee's policy decision around prioritising booster jabs.

Public Health England recently reported that between 96% and 100% of people from "clinical groups" launch an immune response after receiving a coronavirus jab, with "no evidence of reduced vaccine effectiveness".

Nevertheless, the level of protection received by patients with a "chronic illness" and subsequent "immune deficiencies" – either due to "profound immune impairment" or treatments that reduce the immune response – was unclear.

Read more: Mix and match coronavirus jabs produce robust immune response

To learn more, the Octave scientists have recruited more than 2,500 people with "a range of chronic diseases that either intrinsically, and/or as a result of the associated therapies, have impaired immunity". 

"Given the current imperative to inform policy decisions concerning vaccine effectiveness in these vulnerable patient sub-groups," the team has released preliminary data ahead of the results' final release.

The majority of the study's 600 patients were immunised with the Pfizer-BioNTech or Oxford-AstraZeneca vaccines, the first coronavirus jabs to be approved in the UK.

Overall, 89% of the patients generated antibodies against the coronavirus' spike protein, which the infection uses to enter cells, four weeks after their second jab. This is compared to 100% of the 93 healthy individuals in the so-called Pitch study.

In the Octave trial, 11% of the patients "across all disease cohorts fail[ed] to generate antibodies that react to [the coronavirus'] spike four weeks after two vaccines".

This was particularly high among the participants with ANCA-associated vasculitis (AAV) – an umbrella term for immune-induced inflammation of the small blood vessels – with 72% being affected. 

Read more: 45-week gap between Oxford coronavirus jabs triggers 'enhanced immune response'

An antibody response was also not launched in 16% of the patients with liver disease or those on haemodialysis, a machine that filters and cleans the blood if the kidneys have failed.

"Importantly," all of the AAV patients were on the drug Rituximab, "a targeted B cell depletion therapy".

"There are imminent plans in place to investigate the effects of administrating an alternate vaccine dose to the group with an undetectable or low vaccine immune response," said lead author Professor Iain McInnes, from the University of Glasgow.

"We hope these findings will support the role out of an immunological screening programme for vulnerable patients to identify those who will benefit from a subsequent vaccine boost."

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Even among those who did produce coronavirus-spike antibodies, 40% had lower levels than those of healthy individuals.

This affected nearly nine in 10 (87%) of those with Rituximab-treated AAV, just over half (51%) with inflammatory arthritis and more than two in five (42%) who were on haemodialysis, alongside taking an immunosuppressive therapy.

A reduced antibody response was also observed in 36% of the liver disease patients, 33% of those with blood cancer, 20% who were on haemodialysis alone, 17% who had received a stem cell transplant and 10% with a solid cancer, like breast or lung tumours.

"While 40% of these clinically at-risk patent groups were found to have a low or undetectable immune response after a double dose of the vaccine, we are encouraged this figure isn't higher," said Professor McInnes.

"It is possible even partial protection may be clinically beneficial and this is something we will closely monitor."

Professor McInnes pointed out that while 40% of the patients had lower antibody levels, the immune response in the remaining 60% "looks essentially the same as those with an unimpaired immune system".

Coronavirus pandemic, senior woman in self quarantine to avoid contagion of infection by virus covid-19. Stays home looking outdoor from the window. Prevention concept
Many people with a suppressed immune system were told to shield during the height of the pandemic. (Posed by a model, Getty Images)

Spike-specific T cell levels were also "similar to healthy individuals".

"The T cell component is also really important," said co-author Professor Carl Goodyear, from the University of Glasgow. "Antibodies are not the only armour we have in our immune system.

"We don't know yet and studies will hopefully come through [revealing] the functional role T cells play and how that will impact on the the overall pathology of the disease [in an individual]."

Professor McInnes likened the immune system to an airline, in the sense both have "back-up systems".

"Even patients with quite significant immunosuppressive regimes, are launching a T cell response," he said. "That gives us optimism."

Dr Rob Buckle, from the Medical Research Council – part of the UK Research and Innovation body, which co-funded Octave – added: "Today's results will be of concern for the subset of people within those who are immunosuppressed for whom the vaccine didn't trigger a large protective response. 

"We're funding an extension to the Octave study to give third jabs to this group, which we hope will deliver a much-needed immunity boost, or identify those who could benefit from other interventions."

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