Third Covid vaccine dose improves defence for some clinically extremely vulnerable patients

90% who had low immune response during initial vaccinations developed antibodies, but more than half of non-respondents from first jabs saw no booster benefit

Female patient having plaster applied to upper arm after a vaccination given by medical professional

A major clinical trial has found that an additional COVID 19 vaccine dose led to the majority of clinically extremely vulnerable people mounting defensive antibodies against Covid-19.

New research published in The Lancet Rheumatology from the OCTAVE DUO research trial co-led by the University of Birmingham and University of Glasgow found that vaccine boosters led to improved antibody responses among many groups of immunocompromised and immunosuppressed patients.

Co-funded by the Government and Blood Cancer UK and supported by the National Institute for Health and Care Research (NIHR), this trial opened in 11 hospitals across the UK and recruited 804 patients across nine disease areas, all of whom had previously mounted low or no immune response from an initial two doses of the vaccines.

Among those who mounted a low immune response, 90% patients who received a third vaccine dose went onto develop significant antibody levels.

However, more than half (54%) of ‘non-respondents’ from the initial vaccine course still saw no relevant antibody increase. Furthermore, the study found that those with lymphoid disease and chronic renal disease had the worst antibody mounting outcomes from boosters.

It is encouraging to see that boosters helped to increase antibody defences 9 in 10 participants who hadn’t previously mounted a defence after two jabs.

Professor Pamela Kearns

The OCTAVE DUO study also found:

  • some drugs reduced antibody response including treatments for autoimmune diseases and cancers – specifically B Cell targeted therapy and antimetabolites.
  • T Cell response was mounted for 80% of all participants, including more than half (55%) of those previously not showing any T Cells after two vaccinations.

Pamela Kearns, Professor of Clinical Paediatric Oncology and Director of the Institute of Cancer and Genomic Sciences at the University of Birmingham, and a lead investigator of the trial said:

“The Covid booster programme has been shown to have an important protective effect for many of the most clinically vulnerable members of society for whom the initial two doses were insufficient. In the OCTAVE DUO study, we tracked those who mounted little or no antibody defences following two initial doses of a vaccine. It is encouraging to see that boosters helped to increase antibody defences 9 in 10 participants who hadn’t previously mounted a defence after two jabs.

“However, more than half of those who didn’t respond at all to an initial course of vaccines didn’t develop any antibody defence after boosters. This underscores the need for other protective factors to support the most clinically vulnerable in society and continue to be vigilant against Covid in society.”

Professor Iain McInnes, Head of the College of Medical, Veterinary and Life Sciences at the University of Glasgow and Chief Investigator for the OCTAVE Consortium, said:

“Our first OCTAVE study revealed a group of patients who may not mount a sufficient immune response following a vaccine dose, which is why the OCTAVE DUO study is so important. For the clinically vulnerable in our society, the vaccine booster programme offers important protection, therefore further understanding of the effectiveness of vaccines in people with immune-mediated inflammatory diseases is extremely important.

"It is encouraging to see the results of OCTAVE DUO, which provides important answers and reinforces the need to support and protect patients who are more clinically vulnerable.”

Notes for editors

  • For media enquiries, please contact Tim Mayo, Press Office, University of Birmingham, tel: +44 (0)7815 607157.

  • The University of Birmingham is ranked amongst the world’s top 100 institutions. Its work brings people from across the world to Birmingham, including researchers, teachers and more than 6,500 international students from over 150 countries.

  • The University of Birmingham is a founding member of Birmingham Health Partners (BHP), a strategic alliance which transcends organisational boundaries to rapidly translate healthcare research findings into new diagnostics, drugs and devices for patients. Birmingham Health Partners is a strategic alliance between seven organisations who collaborate to bring healthcare innovations through to clinical application:
    • University of Birmingham
    • University Hospitals Birmingham NHS Foundation Trust
    • Birmingham Women's and Children's Hospitals NHS Foundation Trust
    • Aston University
    • The Royal Orthopaedic Hospital NHS Foundation Trust
    • Sandwell and West Birmingham Hospitals NHS Trust
    • West Midlands Academic Health Science Network
    • Birmingham and Solihull Mental Health NHS Foundation Trust

  • About the National Institute of Health and Social Care Research

    The mission of the National Institute for Health and Care Research (NIHR) is to improve the health and wealth of the nation through research. We do this by:

    • Funding high quality, timely research that benefits the NHS, public health and social care;
    • Investing in world-class expertise, facilities and a skilled delivery workforce to translate discoveries into improved treatments and services;
    • Partnering with patients, service users, carers and communities, improving the relevance, quality and impact of our research;
    • Attracting, training and supporting the best researchers to tackle complex health and social care challenges;
    • Collaborating with other public funders, charities and industry to help shape a cohesive and globally competitive research system;
    • Funding applied global health research and training to meet the needs of the poorest people in low and middle income countries.

    NIHR is funded by the Department of Health and Social Care. Its work in low and middle income countries is principally funded through UK Aid from the UK government.