Thread by @VikiLovesFACS

What can vaccines on older platforms tell us about the side effects we might expect to see on the newer mRNA and adenovirus vector platforms? 🧵

This is something I’m asked a lot at the moment, particularly because people want to know if it’s fair to compare the menstrual effects seen with HPV and flu vaccines with those seen with COVID19 vaccines, as I have in this (now oldish) thread. 2/

https://twitter.com/VikiLovesFACS/status/1384916241530380294?s=20

To get at this, we actually have to go back to the basics of how vaccines (on any platform) work. They have to provide two things... 3/

1. The specific thing we want the immune system to respond to, which we call the “antigen”. In the case of the COVID19 vaccines, this is the SARS-CoV2 spike protein. 4/

2. A signal telling the immune system it should make a response. We call this a “Pathogen-Associated Molecular Pattern” or “PAMP. 5/

This signal activates a part of the immune system called the “innate” immune system, which is fast but not specific. The innate immune system then activates the "adaptive" immune system to make a specific response to the antigen and this is what protects us in the future. 6/

Different platforms activate the innate immune system in slightly different ways. For example, the old-fashioned attenuated (weakened) viral vaccines activated the immune system by *actually being viruses*, which have their own PAMPs. 7/

The adenovirus vectored vaccines work in the same way - they are actually viruses with PAMPS. 8/

The mRNA-based vaccines we are currently using also activate the immune system by looking a lot like a virus. Before these vaccines were invented, viral infection was afterall the usual way to end up with foreign RNA inside a cell! 9/

Finally, for completeness, vaccines that are made with killed viruses or protein subunits of various kinds don’t have PAMPs. So we have to add PAMPS (or something like them) to get them to work. This is called an “adjuvant”. 10/

Here is a collection of infographics from the @britsocimm that explain this for a general audience... 11/

immunology.org/coronavirus/co…

And if anyone would like molecular detail on how mRNA vaccines “trick” the immune system into thinking they are viruses, here’s a paper on that... 12/

…nslational-medicine.biomedcentral.com/articles/10.11…

So what does this tell us about side-effects? Well, you may have noticed that all vaccines, no matter whether they are killed virus, weakened virus, adenovirus vectored or mRNA, have a similar set of short-term side-effects. Sore arm, temperature, feeling tired etc... 13/

That’s because all these effects are caused by the innate immune response. This gets activated in slightly different ways by different platforms, but fundamentally what causes the side effects is the innate response, which is the same across all of them. 14/

To circle back to the question of whether effects on the menstrual cycle, I think it’s particularly striking that we seem to see these associated with both mRNA and adenovirus-vectored COVID vaccines, as well as the reports we’ve had before on HPV and flu vaccines. 15/

To me, this suggests that menstrual cycle effects may well be mediated by the innate immune response and are quite possibly associated with all vaccines. 16/

It may be the case that we’re noticing them now because this is the biggest vaccination campaign we’ve ever done that has included people who have periods. 17/17