A Third COVID Vaccine Dose Improves Defense for Some Clinically Extremely Vulnerable Patients

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.

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% of 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.

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 program 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 defenses following two initial doses of a vaccine. It is encouraging to see that boosters helped to increase antibody defenses 9 in 10 participants who hadn't previously mounted a defense 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 defense 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 vaccinebooster program 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."