Issue #53: Going on trial, getting (the) shot and signing the forms

Written by Nobel Laureate Professor Peter Doherty 

Our medical doctors and nurses who have direct patient contact at The Royal Melbourne Hospital (RMH) were, together with the laboratory scientists and technologists who work with fully infectious SARS-CoV-2, given the Pfizer BioNTech (PB) vaccine (#43) in the Phase 1A, front-line healthcare worker (HCW) ‘first wave’ of the national vaccine rollout. Being in the Phase 1B cohort as a consequence of age, I called up and got my wife Penny and I on the list as soon as I saw the e-mail announcing that the University Health Clinic was signing-up candidates for the AstraZeneca (AZ) shot (#43).

Part of the motivation for doing this as early as possible was that Eureka Prize and Emmy Award-winning film-maker Sonya Pemberton – who made the wonderful Jabbed documentary on vaccination that featured some years back on both SBS and the US PBS Network – has been doing a story on COVID-19 that focuses in part on the work of the Doherty Institute. It’s due to air on the ABC around, or before, mid-year, and, as Sonya drove ahead to wind-up the editing process, she insisted that video of us making our way to, then getting the vaccine shot was part of her storyline. You can meet Sonya and see something of Jabbed here.

Calling up the University Clinic on the Monday we were, along with video crews from both Sonya’s team and the Doherty Institute, organised to present ourselves for the shot on that Friday. But the vaccine didn’t arrive, so we made a further date for the following Wednesday. Turning up early, we then went through the whole filming performance that’s necessary to create a visual storyline. From time to time, that’s been a minor part of our life since the 1996 Nobel Award.

Before that, further to letting Sonya and our media people know that we had an appointment at the vaccination clinic, my next step was to contact Siddhartha Mahanty who, as part of our medical team working between RMH and the Doherty Institute, had gone through the detailed process of designing, then getting the approvals for, a clinical trial aimed at characterising antibody responses to both the PB and AZ vaccines. As a participant, signing up for a trial means providing relevant personal details by answering various questions on an appropriately designed ‘informed consent’ form.

That done, Siddhartha organised for me to be bled by a phlebotomist (a research nurse) so that ‘before’ serum samples (stored in a deep freeze) would be there to provide the negative baseline for the series of ‘after’ bleeds to monitor the progression of my vaccine-induced antibody response. That initial contact involved taking 63ml of blood into a number of those familiar, negative-pressure ‘vacutainers’ that suck blood out once the double-ended needle is first sitting happily in your vein, then penetrating the rubber cap of the collection tube. The first post vaccination bleed, which required a much smaller volume, was seven days after the AZ jab.

I’d also let my long-term colleague Katherine Kedzierska who has, over the years, moved much of our T cell-mediated immunity (#18 #33) research program from mice to humans, know that I was enrolling in Siddhartha’s trial. That led immediately to my signing a separate informed consent so that my blood samples could also be used in Katherine’s trial, with her interest being more in the white blood cell (WBC) fraction (#7) than the serum. Katherine’s laboratory is pursuing a detailed analysis of COVID-19 vaccination versus SARS-CoV-2 infection-induced T cell and B cell responses (#18), using sophisticated molecular and cellular technologies established earlier for studying influenza.

By the time I’d been accepted into these two clinical trials, then had the vaccine shot, I’d signed three different ‘informed consents’, one for each trial and one for the administration of the vaccine. As part of that process, I acknowledged that I’d read, in plain English, a summary of possible risks, and that I’d agreed to take those risks. Every medical intervention is, like crossing the street, a risk/benefit equation. In particular, we must be clearly informed about any level of risk when we are signing up to be human ‘lab rats’ in a research protocol. And an essential part of the ethical approval process for such trials requires that the acceptable risk is appropriate for the perceived benefit https://www.tga.gov.au/clinical-trials.

Protection from severe disease, the intended benefit of getting the vaccine, is obvious (#21). Because of the nature of these trials I will, somewhat unusually, eventually have the benefit of knowing how the vaccine has worked for me (#40). In general, the best correlation of protection will likely be the level of SARS-CoV-2 specific antibodies in my blood (#21 #52). That I would learn from Siddhartha’s trial but, by signing on to Katherine’s research protocol, I hope to learn more about my own cell-mediated immune response, the subject I’ve now worked on for almost 50 years. Both these observational trials are restricted to personnel at RMH and the Doherty Institute, so they aren’t taking members of the broader public. More next week about clinical trials and how you might sign-up if you want to be involved. We’ll also talk more about informed consent, risk/benefit and the evolving story of what’s happening with the AZ vaccine.