Phase 1 trials are used to determine dosage. Different participants are given different doses of the vaccine so researchers can identify the proper dosage with maximal efficacy and minimal side effects.

The 29 year volunteer who experienced the 103° fever received the highest dose of the vaccine given out during the Phase 1 trial. Such a adverse reaction is not unexpected during a Phase 1 trial, but the vaccine did move forward to Phase 2 and Phase 3 so it appears that the lower dosages do not trigger such a reaction.

Even the "mild / moderate" reactions were pretty bad though. They sounded substantially worse than your average cold.

It’s disingenuous to call it “the Moderna mRNA vaccine” when it was more accurately “one early Moderna mRNA vaccine candidate, which was ruled out for being far too high of a dose”.

Thanks for the valid correction.

I didn’t mean to be disingenuous. I forgot they rejected that dosage.

Overall, the picture does look potentially concerning for the side effects of that vaccine and efficacy is still unclear.

What makes it concerning? Tylenol is concerning if you take 2.5x the safe dose. Of course the efficacy is unclear — it’s still in trials!

There was a pretty high severe systemic adverse rate in the high dose group (20%). Severe local response rate was 5% in the middle dose. [1]

I have no idea how this compares to other vaccines, and you can pessimistically extrapolate a bit from this tiny, healthy sample from the high dose (n=15 in middle dose group).

I'd imagine some % of people when this scales to millions will have a bad response, and the high dose group might provide some model of the worst cases.

[1] https://www.nejm.org/doi/full/10.1056/nejmoa2022483

I think the comparison most are making is to Shingrix. Have a look at Table 2[1].

[1] https://www.nejm.org/doi/pdf/10.1056/NEJMoa1603800

That was at the 250ug dose, current dose is 100ug. At that dose, even the elderly didn’t have bad side effects.

Fevers are very common in vaccines, normally. It is an indication that the immune system developing an immune response. It is not an indication of complication.

Yes, but at some threshold wouldn’t this indicate a problem?

103F+ fevers are relatively rare from typical vaccines, and from my understanding a lot of the damage from COVID is immune response related.

mRNA vaccines and our immune responses to these are uncharted territory, so I’m not sure how much we can reason by analogy from other vaccines vs. first principles.

High fevers are not uncommon in babies receiving their first vaccines.

I'm not sure it indicates a problem. A fever is, itself, just an immune system response, not a "symptom" of disease.

You are correct that there is a threshold beyond which a fever becomes unsafe, but it's above 103. But fevers of 103 in the test group do not indicate that fevers of say 105 will occur in some patients.

mRNA would not have hit Phase III if found unsafe in earlier phases. If mRNA succeeds things will look really great, since it in principle it can protect against many other viruses and upcoming pandemics with slight modifications. The most reported side effect for mRNA is mild stiffness at application spot.

The idea a vaccine can be safely made in less than a year is absolutely insanity. Many of these things shouldn't even be considered vaccines in the traditional sense.

Are there any vaccines out on the market today that are not one of the two: 1) inactivated virus, 2) attenuated virus (run through another host/egg or a related virus found in an animation that's less harmful to humans)?

Everything I've found indicates all our current viral vaccines are one of those two (excluding bacterial vaccines, which shouldn't be called vaccines either).

The modeRNA vaccine is an mRNA vaccine, a completely new type of vaccine. While theoreticall less likely to have adverse effects, it did have adverse effects, and its efficacy remains a question. These are completely new types of vaccine, that presumably would need even more testing than the relatively well understood attenuated viruses.

> modeRNA

I can't believe I didn't notice that until now.

> completely new type of vaccine

Then is it a vaccine at all? Vaccines were traditionally live, dead, or attenuated virus/bacteria injections, some with adjutants, to stimulate an immune response.

Technologically speaking, it's bicycle vs airplane. Similar underlying purpose, entirely different implementation.

Both a bicycle and an airplane are transportation vehicles. Likewise, anything that illicits imunity is a vaccine, regardless of how novel the approach is.

Every time we see or hear an expert on the topic of COVID-19 vaccines, she/he is either circumspect to the point of pessimism (this is rare, but see e.g. Robert Gallo) or obviously trapped in a spiral of wishful thinking (this is common). We've never made anything like this hypothetical drug. Forget about election day. I'll be surprised if we have a commonly-available and effective COVID vaccine in 2021.

Not the question you asked but the Chinese company Sinopharm has started phase 3 trials of a classic inactivated virus vaccine (and Bharat Biotech is starting phase 2 trials as well in India). The difficulty will be mass-producing it, of course, but we aren't necessarily reliant on novel vaccine technologies.