Thread by @podehaye

In 2007, I participated in an Oxford vaccine trial. This was the 1st time chimpanzee adenoviruses were tested on humans. I was the second to be injected w/ this stuff.

The Oxford/AstraZeneca COVID vaccine is directly based on that tech, with tremendous hope beyond COVID

👇

2007 was a touchy time to participate in a vaccine trial. The year before a trial for Theralizumab had resulted in 6 volunteers out of 8 suffering a cytokine storm. One of the 6 lost toes and fingers. The last two? They had only received placebos!

en.wikipedia.org/wiki/Theralizu…

As a consequence, the Oxford Jenner Institute had trouble recruiting volunteers for their trials. One of my fellow @MertonCollege Fellows explained to me the science and the goals for their 2017 campaign and convinced me to participate.

The idea was to take a protein insert known to induce an immune response useful vis-à-vis malaria, and to stick it on a non-recombinant chimpanzee adenovirus. The human immune system would be virgin to such an intrusion and react more specifically to the protein insert.

I thought that was so cool! As explained to me the goal was clearly to build a new approach to creating a vaccine. How often do you get to contribute to that?
This below is the official Participant Information Sheet.

I was in Subgroup 1A.

Pages 1-4

Pages 5-8.

I was compensated (not paid!) 20GBP per trip, 5.50GBP per hour, 6 GBP by blood sample.

Pages 9-12. Page 11 omitted due to personal numbers (for emergencies). Page 12 is the consent form.

This is the official registration for the vaccine trial. The chimpanzee adenovirus they were using is called ChAd63 when considered as a "vaccine vector".
clinicaltrials.gov/ct2/show/NCT00…

This is the publication that resulted from the study. Not overly flashy, but, essentially: "it's safe and generates more potent response than previous malaria vaccine attempts".
pubmed.ncbi.nlm.nih.gov/22275401/

Now that they had outlined a valid approach, the Oxford researchers set out to refine it. They had two components to play with: the platform and the protein insert. The insert is disease specific, while the platform is generic.

For the platform, it's best when it has as low human seroprevalence as possible. They found a new type, which they called ChAdY25 then renamed ChAdOx1, which seemed to be more globally rare.

europepmc.org/article/PMC/33…

They knew ChAdY25 and ChAd63 were different because the sera collected from my study didn't react to ChAdY25. This validates the idea that one could have concurrent vaccination programmes based on two different vectors.

They also got to varying the disease-specific protein inserts. This fascinating 2017 review article lists all these attempts beyond malaria: HIV, Ebola, rabies, influenza, tuberculosis, hepatitis, etc.

tandfonline.com/doi/pdf/10.108…

The rest is history: once COVID arrived, they had all the understanding they needed in order to design a vaccine (and for once the resources for this). The Oxford COVID vaccine is based on ChAdOx1.

thelancet.com/journals/lance…

For the production aspect - which they had never explored at that scale - they still needed help from AstraZeneca ("we are out of our depth").

But they knew the vaccine would be cheaper and easier to deliver than the mRNA ones, hence more equitable.

https://twitter.com/patrickwintour/status/1344204840935813122?s=20

(Remember, we are returning to "normal" fast. I can't believe we haven't really started talking about this globally:)

Looking back at all the whole intellectual progress there, two aspects really are fascinating.

1/ With all this validation, attention, money, etc, there is real promise to make progress on all these established diseases using similar techniques. BUT... each time we will make an attempt, we will have to "burn" an obscure chimpanzee adenovirus in order to do so.

2/ for as long as mRNA vaccines remain expensive and hard to deliver, our best protection against future species-hopping pandemics will probably be in *preemptively* "vectorizing" benign diseases from our *closest* species. How crazy of a trick to our immune system is this?

Congrats to all the teams involved in this! /end

This would include @geraldineaohara, who was my main contact, @S1monJDraper who convinced me, @NDMOxford @UniofOxford @JennerInstitute, and a lot of @MertonCollege members who participated over the years, including some who continue to this day!

merton.ox.ac.uk/merton-respons…