I am curious about what actually goes into a vaccine placebo formulation, given that there were apparently some reactions reported by trial subjects who received the Pfizer SARS-CoV-2 placebo.

From what I've been able to find out online, the actual vaccine contains as principle ingredients (simplified):

  • mRNA (active ingredient) to make the target antigen (spike protein)
  • lipids (to protect the mRNA and facilitate its delivery into cells)
  • salt(s) to adjust pH and match the salinity of blood
  • sugar to address issues which occur when the vaccine is frozen

An injectable placebo could be as simple as a saline solution... if so, how could reactions be explained? Is it entirely psychosomatic? Is the Pfizer SARS-CoV-2 trial placebo the complete formulation (or some subset of vaccine components) minus the active (mRNA) ingredient?

The lipids have been implicated in allergic reactions to the actual vaccine; would they have been present in the placebo and account for the placebo reactions?


1 Answer 1


Simple answer: This vaccine trial compared their trial vaccine against saline. See the original publication by Biontech and Pfizer in the New England Journal of Medicine linked below. The relevant information can be found in the methods section:


With the use of an interactive Web-based system, participants in the trial were randomly assigned in a 1:1 ratio to receive 30 μg of BNT162b2 (0.3 ml volume per dose) or saline placebo. Participants received two injections, 21 days apart, of either BNT162b2 or placebo, delivered in the deltoid muscle. Site staff who were responsible for safety evaluation and were unaware of group assignments observed participants for 30 minutes after vaccination for any acute reactions.

As far as I followed up the case of the allergic reactions, two of these have been observed in England. Both people had an epipen injector for such cases by hand, making it possible that they have underlying problems with allergies (as this is not a medical device people usually have at hand), no such cases have been reported from the trial. Allergic reactions are always a small risk with vaccinations which is the reason why this is done in a controlled medical environment.

As for the vaccine reactions in the placebo group, this can be caused by the nocebo effect, where expecting negative effects leads to a more negative reaction. As @BryanKrause mentioned, all possible effects reported in such trials are recorded as possible side effects. This leads to a lot of things being recorded which happened at the same time as the vaccination but have no connection to it.

Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine

  • 7
    $\begingroup$ In addition to the nocebo/psychogenic effects, I think it's worth mentioning that people experience things classified as "side effects" all the time. People get headaches, diarrhea, sneeze, cough, get stiff limbs. Ordinarily we shrug it off, blame it on last night's meal, how we slept, smells from the neighbor's cooking. But if you just got injected with something that might have been a vaccine, it's natural to attribute it to that thing that's novel. $\endgroup$
    – Bryan Krause
    Dec 12, 2020 at 23:40
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    $\begingroup$ @BryanKrause Good point. It demonstrates the old "correlation is not causation" very well. $\endgroup$
    – Chris
    Dec 13, 2020 at 10:47

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