Thread by @PrEP4AllNow

Since December, we have been warning everyone that would listen that the world's overreliance on adenoviral vectored vaccines for COVID-19 was dangerous. This news from 🇿🇦 shows why. Mini- 🧵: dailymaverick.co.za/article/2021-0…

As the virus mutates, we will need to change the design of the vaccine to combat new variants. But adenovirus vaccines are particularly challenging to develop these new variant busting boosters for two reasons.

First, the production of a given adenovirus vectored vaccine requires the generation of a "master cell line", engineered HEK293 or PER.C6 cells that can stably and productively express the vector to make the vaccine drug substance. Much effort is spent on this.

If you need to change the vaccine design, you need to either modify the master cell line used or reengineer (and select) a new one. And re-optimize the production process for the new/modified master cell line. But this is tricky and slow.

@JNJ is the world's 5th largest producer of cell-line derived biopharmaceuticals, and they are months behind production of their Ad vectored vaccines due to production issues. nytimes.com/2021/01/13/hea…

2. Adenovirus vectored vaccines likely induce a immune response to the vaccine itself ("anti-vector" immunity). This may reduce the efficacy of subsequent booster shots. Some vaccines (like Sputnik V) use 2 different vectors (Ad26/1st and Ad5/2nd) to get over this.

But that is just for the first and second shot! We can't just use another vector for each subsequent booster shot. In fact, there are already a potential safety problem with Sputnik V because the Ad5 vector may be associated with increased HIV acquisition risk.

Ultimately all of these reasons (and more) is why we have called for a dramatic scaling up of mRNA vaccine production for COVID-19 vaccination. The (nearly) cell-free production process means changing the vaccine design for a new variant is relatively fast and simple.

And the lack of a viral vector (a mRNA vaccine uses a lipid nanoparticle instead) means that there is not really a large risk of anti-vaccine immunity precluding a mRNA vaccine from being immunogenic on subsequent booster shots! Read more: nytimes.com/2021/01/12/opi…