Some immunosuppressed patients mount an almost undetectable antibody response after two jabs, and may benefit from a booster COVID-19 vaccine

vaccine older lady

There is a convincing case to support rolling out booster COVID-19 vaccines to some people with impaired immune systems to help optimise antibodies to SARS-CoV-2, scientists have said.

The comments followed results from a study that suggested that a significant proportion of clinically at-risk patients with some conditions causing immunocompromise or immunosuppression mount a low, or undetectable, antibody immune response after two doses of a COVID-19 vaccine.

Initial data from the Observational Cohort Trial-T-cells Antibodies and Vaccine Efficacy in SARS-CoV-2 (OCTAVE) study was reported in a preprint on 23 August 2021.

The findings suggest that around 60% of patients in the study’s groups mounted an immune response that looks similar to that seen in healthy control subjects. However, around 40% had a low or undetectable immune response.

The research—a multicentre, UK-wide trial led by the University of Glasgow and coordinated by the University of Birmingham’s Cancer Research UK Clinical Trials Unit— set out to evaluate immune responses following COVID-19 vaccination in people with immune-mediated inflammatory and chronic diseases. These included people with inflammatory arthritis, diseases of the kidney or liver, and cancer, and patients undergoing a stem cell transplant.

Preliminary results 

The early data, based on around 600 participants from a much larger cohort, were compared with those from 231 healthy people from the Protective Immunity from T cells in Healthcare workers (PITCH) study.

The researchers report that, although all individuals tested in the PITCH study generated antibodies against the SARS-CoV-2 spike protein after two doses of either the Pfizer/BioNTech or AstraZeneca/Oxford vaccine, only 89% of patients within OCTAVE seroconverted 4 weeks after a second dose.

Antibody levels were dependent on the patients’ diseases. The percentage of patients responding less well than the lowest levels seen in healthy subjects was highest in those with:

  • antineutrophil cytoplasmic antibody-associated vasculitis treated with rituximab (87%)

  • inflammatory arthritis (51%)

  • renal failure on haemodialysis and immunosuppressants (42%)

  • hepatic disease (36%)

  • renal failure on haemodialysis (20.3%).

The lowest numbers of patients with poor antibody reactivity were seen among patients with solid cancer (10%), and those with haemopoietic stem cell transplant (17%).

Professor Iain McInnes, Vice-Principal of the University of Glasgow, who led the study, told a briefing hosted by the Science Media Centre: ‘The majority of the patients in the OCTAVE trial actually have mounted an immune response that looks remarkably similar to a healthy control group.’

Furthermore, their outcomes were being compared with an ‘optimal group’ consisting of people who were, on average, younger than the OCTAVE cohort.

He also stressed that even patients who mounted no antibody response after vaccination could be protected by a T-cell response.

‘We’re quite reassured that even patients on quite significant immune suppressive regimes are mounting this cell response, this T-cell response, and that gives us optimism that there is indeed a degree of virus protection, even for those whose antibody levels may be negative.’

Booster vaccine study 

When asked whether patients with an impaired immune system may benefit from a booster vaccine, Professor McInnes said: ‘Our data suggests that a booster for people who have mounted either an absent or lower level of antibody response would be a very reasonable next step.’

The researchers had already begun a separate trial, called OCTAVE DUO, to address that question, he said.

It will involve patients randomised to receive either the Pfizer or Moderna vaccine, with a small subgroup given a third dose as a booster with the Novavax vaccine. 

‘Comprehensive study’ 

Commenting, Dr Doug Brown, Chief Executive of the British Society for Immunology, described the paper as ‘one of the most comprehensive studies to date’ on the subject.

He said: ‘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.’

Eleanor Riley, Professor of Immunology and Infectious disease at the University of Edinburgh, said the research showed that many of the patients in the OCTAVE trial ‘did make a detectable antibody response, and their response went up again after the second dose of vaccine’. It was, therefore, ‘quite possible that they will make an even better response after a third dose of vaccine’, she said.

This article originally appeared on Medscape, part of the Medscape Professional Network.