Comment by precog on How the Moderna vaccine works, and a note about mRNA vaccines · 2020-11-17T23:11:56.826Z · LW · GW

My response from reddit:

Pfizer developed multiple candidates, not all of which were self-amplifying. The one that they have progressed the furthest in the clinic is not self-amplifying. The 2P modification does not just stabilize the spike antigen against transition to the postfusion state after contact with ACE2, it stabilizes it in prefusion form generally. The Spike without the 2P modification is unstable to multiple conditions besides ACE2 contact and is harder to express in cells. It's also worth noting that this modification is also in the spike antigen encoded by Pfizer's vaccine, and that it was not discovered by either of these companies but rather by Jason McLellan's lab in collaboration with the NIH.

Saying 'the good thing about the vaccine is there are no viral particles' doesn't really make sense. What's good about not having viral particles? Virus-like particles and inactivated virus are both vaccine forms that have viral particles which have well-demonstrated safety and efficacy and have been FDA-approved. In contrast, there are no FDA-approved mRNA vaccines and these vaccines have the disadvantage of containing other elements (ionizable and PEGylated lipids) which we might not necessarily want to generate an immune response against.

Saying it gets a better immune response than 'normal COVID' doesn't have much basis in fact and is probably wrong. In my opinion, natural infection is actually more likely to produce a 'better' immune response as it is more likely to produce antibodies and SARS-CoV-2-specific T cells in the upper respiratory tract and mucosa. This has the potential to result in 'sterilizing immunity', such that the virus cannot establish a foothold and replicate. You will notice that the definition of efficacy for the current vaccine candidates is preventing disease rather than preventing infection. This is because intramuscularly-administered vaccines are generally poor at inducing mucosal immunity, which is the kind of immunity needed to prevent infection by strengthening protection at your mucosal barriers. This is usually most effectively induced by natural infection or by intranasal vaccination.

EDITED TO ADD: Sterilizing immunity is desirable because preventing viral infection and replication prevents transmission. If all your vaccine does is prevent disease after infection, then you could conceivably still get infected and spread the virus/disease to others.