Protein-based COVID-19 vaccine produced fewer day-one reactions than mRNA

Design

double-blind randomised controlled trial, 1:1 allocation, solicited symptom surveys

Population

901 adults with at least two prior mRNA doses (448 protein-based, 453 mRNA)

Primary outcome

solicited systemic and local events on days 1, 2 and 6

Effect

day-one systemic events 62.1% vs 75.7%, risk difference -13.7% (95% CI -19.6 to -7.7)

Within the randomised, double-blind BEEHIVE trial, 901 participants who had already received at least two mRNA doses were assigned 1:1 to one dose of the 2023-2024 XBB.1.5 formulation of either the protein-based or the mRNA vaccine. Solicited events were collected by electronic survey on days 1, 2 and 6.

On day one, 62.1% of the protein-vaccine group reported a systemic event against 75.7% of the mRNA group, a risk difference of -13.7% (95% CI -19.6 to -7.7). Local events were 81.0% against 92.7%, a difference of -11.7% (95% CI -16.0 to -7.3). The mean number of events per person was also lower on day one for both systemic and local reactions, and on day two for local. Most events were mild, and by day six more than 80% reported no systemic and more than 94% no local reactogenicity in either group.

This is reactogenicity, not effectiveness - the trial compared how people felt afterwards, not how well they were protected. That is still the variable that decides whether a healthcare worker takes a booster before a night shift, and the one patients ask about. Both vaccines produced local reactions in the large majority.

• Systemic reactions on day one were about 14 percentage points less common with the protein-based vaccine.
• Most reactions in both groups were mild and had settled by day six.
• This compares tolerability only, and says nothing about relative protection.
• Local reactions affected most recipients of either vaccine.
• Useful when counselling someone who avoided a booster because of a previous reaction.

Why it matters

Reactogenicity is the reason many healthcare workers skip a booster, so a measured difference in it is a usable counselling fact.

Don't overread it

A reactogenicity comparison only - it does not establish that either vaccine protects better or worse.

The statistics, in plain English

Both risk differences have confidence intervals well clear of zero in roughly 450 people per arm, so the reactogenicity difference is solid. What the trial does not report here is any measure of immunogenicity or protection, and a milder reaction is not evidence of a weaker or stronger immune response - the two are frequently assumed to track together and do not reliably do so.

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