Issue #55: My World Immunisation Week

Written by Nobel Laureate Professor Peter Doherty

As I write this, we’re again in World Immunisation Week (WIW), so I’m pausing my exploration of clinical trials (#53, #54) to reflect a little on what’s happened since I first wrote around this topic. Back then (#4), I reflected on the deep history of immunisation/vaccination and promised further commentary to follow. As the year progressed, my main focus was to tackle the basics of infection and immunity in ways that might be comprehensible, useful and maybe even entertaining for a general reader. In general, the immune system is infinitely complex, so there is a way to go with that! Still, as COVID-19 vaccine rollouts began seriously in the northern hemisphere from early 2021, it was obvious that I could procrastinate no longer re discussing vaccines. Hopefully, what I’ve written in #43 – #52 has been of some use. There will, as events unfold, undoubtedly be more to follow.

The big surprise was, of course, the incredible effectiveness of the completely novel (for human use) mRNA vaccines (#43 – #52) when it comes to protecting large numbers of people from the more severe clinical consequences of COVID-19. Much remains to be understood re the durability of this immunity and how exactly these vaccines are working.  The alternative adenovirus-vector strategy, the basis of the AstraZeneca (AZ) vaccine (#43) that is now available to most Australians has, on the other hand been around for quite a while. Even so, apart from the experimental use of adenoviruses in gene-therapy, the only approved rollout of adenovirus-vectored vaccines prior to COVID-19 was to protect people against Ebola virus infection in Africa. There, the risk benefit equation is obvious.

With regard to the current, widely publicized concerns about the AZ vaccine triggering the potentially fatal CVST (cerebral venous sinus thrombosis) and DIC (disseminated intravenous coagulation) clotting syndromes, that problem only became apparent – the alarm bells were first sounded in Norway – after large numbers of doses had already been given. In a situation where COVID-19 is raging, the risk/benefit equation is still obvious, but that’s less true for Australia where, while our population remains extraordinarily vulnerable, a strong public health response is, at the moment, keeping us safe. I’ve had the AZ vaccine shot (#53), but people under 50, particularly women, are at greatest risk of this particular side effect. The age susceptibility profile associated with SARS-CoV-2 infection is, of course, exactly the reverse for an immunologically naïve (unvaccinated) person, so that influences the risk/benefit calculation. There are also other adenovirus-vectored vaccines out there, including the Russian “Sputnik V” and the Johnson & Johnson product which, after being paused temporarily by the US FDA (Food and Drug Administration) regulator, is again going into people’s arms in the USA.

With regard to what seems to be an adenovirus-trigger for the vaccine-related CVST and DIC problems, one hope is that, by understanding better what’s happening here at a molecular level, it might be possible to ‘tweak’ the formulation of these effective (and cheap to make) vaccines in order to minimise any danger. It’s intriguing to speculate how that might be tested, as neither the CVST nor the DIC complication showed-up in 30,000+ participant, Phase 3 clinical trials. Another possibility is that genomic analysis comparing vaccinated people who have developed this problem with those who have not might lead to a genetic marker identifying those at risk. If so, it would be expensive, but perfectly feasible to pre-screen before giving anyone such products. The third possibility is that clinical haematologists will find better ways to treat both CVST and DIC so that the consequences are neither long-term nor fatal.

Returning to WIW for 2021, my first commitment on Sunday week ago was a 90-minute Zoom presentation at the South Shore Science Festival held in Quincy, a suburb of Boston, Massachusetts. The attendees were, as I understand it, largely school children. Later in the day, I was reminded that I’d failed to return my assessments as a judge for the Art Prize awarded by the Australian Immunisation Coalition in association with the concurrent Influenza Action Week 2021. On Friday, the same group arranged for me to be publicly recorded (on video) receiving the current ‘high test’ (for geriatrics) influenza vaccine. Thankfully, we no longer do public hangings, but there is evidently some enthusiasm for seeing people being jabbed with needles!

During this WIW, I should have been in Washington DC to participate in the Nobel Prize Summit 2021: Our Planet Our Future (April 26-28), a first-ever event organised by Stockholm’s Nobel Foundation and the heavy-hitting US National Academies of Science, Medicine and Engineering. Originally focused on climate change and sustainability, COVID-19 forced the switch to both a virtual format and more emphasis on ongoing pandemic risk as part of the discussion. As a consequence, chaired by author Laurie Garret (The Coming Plague) and featuring fellow panellists NIAID Director Tony Fauci and 2020 Chemistry Nobelist Jennifer Doudna (with Emmanuelle Charpentier for CRIPR-Cas9 gene editing), I participated in a recorded discussion that aired during WIW.

And, as it was also Melbourne Knowledge Week, it was a real delight to join with Victorian Government Minister Jaala Pulford, Chief Scientist Amanda Caples and other distinguished participants in an in-person event at Melbourne’s Federation Square celebrating the State’s long, continued and expanding dedication to the support of health research and innovation. That’s worth a further essay! Next week: back to clinical trials.