The OCTAVE Study: Scaling up our understanding of vaccine effectiveness in people living with autoimmune conditions

Last week researchers based at the University of Glasgow released preliminary data from their analysis of 600 immunocompromised patients participating in the OCTAVE study. This MRC-Funded research project, one of the largest of its kind, is studying around 5,000 clinically at-risk participants with the aim of determining how the immune systems of these people, weakened by their condition or the medications they take, respond to COVID-19 immunisation. These important findings will steer government policy on booster shots and possibly guide the usage of alternative therapies like the recently approved Ronapreve.

How will OCTAVE tell us about vaccine effectiveness?    

In this first paper published from the OCTAVE study researchers compared the anti-COVID 19 antibody and T cell levels in the blood of 600 patients before vaccination, after the 1^st dose and 4 weeks after receiving the second dose of either the Astra Zeneca or Pfizer vaccines. Participants had an array of conditions such as cancers, end-stage kidney disease, liver disease, gastrointestinal conditions, autoimmune rheumatic diseases, or had received stem cell transplants. The common underlying factor within this group was that all had weakened immune systems. To understand how these conditions/ or the medications taken could alter immunity their immune responses to vaccination were compared to those of health workers participating in a similar study called the PITCH study.  

What immune responses should be generated after vaccination?

When a person is vaccinated with the COVID-19 vaccine, the immune system builds an army of responders capable of ‘neutralizing and destroying’ the COVID-19 virus upon future encounter(s). B cells, produce and secrete antibodies into the blood and mucosal sites, like the body tissue lining the mouth and nose. These antibodies ‘neutralise’ virus preventing it from entering a person’s cells and minimizing the chances of a person becoming ‘infected’.

Another cell type called the T cell recognizes and kills COVID-19 infected body cells with speed and precision. Fighting infection once it has taken hold. These cells may also ‘help’ B cells to make antibodies needed to neutralize the virus.

The Neutralizers: A look at antibody responses  

Antibody levels are often used to determine whether vaccination has worked in a particular group of patients. This is because these important molecules, can be easily detected in the blood.

The OCTAVE research team discovered that the 89% of OCTAVE participants generated antibodies in response to two doses of COVID-19 vaccine whereas no antibodies were detected in 11% of OCTAVE participants. An in-depth analysis of this ‘non-responder’ group revealed that these ‘antibody non-responders’ were patients with severe vasculitis, all receiving treatment with a drug called rituximab which works by suppressing our ‘antibody factories’, the B cells.

Those who did generate antibodies fell into two distinct groups. 60% of the overall OCTAVE participant pool fell into a ‘high responder’ category, generating strong antibody responses equivalent to those seen in ‘healthy’ PITCH study volunteers. The remaining 29% were classed as ‘low responders’ with significantly lower antibody levels in the blood after two doses of vaccination. It was within this latter, low responder group that many of the patients with autoimmune rheumatic diseases were found. An in-depth data analysis has not yet been carried out to explain why this is the case, but this could be linked to other factors such as medications taken.

The Killers: What about T cell responses?

Through studying participants T cell responses following vaccination OCTAVE goes further than most studies of this type, which have been carried out in smaller numbers of patients and have only studied antibodies. Positively, and in contrast to the story told by antibody levels, the researchers discovered that all patients had detectable T cell responses after two doses of COVID-19 vaccine, with the numbers and the type of T cell responses comparable to those detected in the PITCH cohort of healthy volunteers.

What does this mean for those with systemic sclerosis?

At present it is difficult to draw any firm conclusions from this work and more research is required to put these findings into context.  Population studies like the Office of National Statistics study will help us understand how anti-COVID antibody levels decline with time, after vaccination and/ or natural infection. This study will also assess the correlation between a decline in antibody numbers over time, and the chances of reinfection from COVID-19.   Further research focused on immunocompromised individuals should aim to understand the influence of medication on immune responses to vaccination. These data combined with information coming from ‘mix and match’ studies where participants receive different vaccines as their first and second doses i.e.  having Pfizer as dose 1 and Astra Zeneca as dose 2 could also add to this area. Indicating how immunity can be ‘tweaked’ to amplify antibody and/or T cell levels as required.

Whatever a person’s antibody levels are they should be reassured that are not completely unprotected since all of those studied no matter their antibody levels had ‘normal’ T cell responses; meaning that their immune systems should be able to destroy virus through the removal of any infected cells.

Back to antibodies, all is not lost for the ‘low responders’, OCTAVE contained some patients who had and recovered from COVID before joining the study and vaccination. These patients had higher antibody levels than others within their patient group providing hope that a third dose of vaccine in the form of a ‘booster’ shot could convert low responders into high responders. Data from transplant patients lends further support to this idea.  

The OCTAVE DUO study will test the effects of a 3^rdbooster dose on 1,200 OCTAVE participants, these individuals will be followed until mid-2022 to understand longer term effects on anti-COVID-19 immunity. Research could help delineate the benefits of newly approved therapies like Ronapreve for either those who are unable to make an antibody response or those who are not boosted by a third dose.

At SRUK, we will update you as more data emerges. In the meantime, we encourage you and your loved ones to follow the latest guidance relating to vaccination and booster shots as it emerges, to check out our updates to the COVID section of the SRUK website and contact us if you need any advice.