A protein COVID vaccine caused fewer early reactions than an mRNA one

Design

Double-blind randomised controlled trial, 1:1 allocation

Population

901 adults with at least two prior mRNA doses (448 Novavax, 453 Pfizer-BioNTech)

Primary outcome

Solicited systemic and local reactogenicity on days 1, 2 and 6

Effect

Day-1 systemic 62.1% vs 75.7% (RD -13.7, 95% CI -19.6 to -7.7); local 81.0% vs 92.7% (RD -11.7)

In a double-blind randomised trial (BEEHIVE), adults who had already had at least two mRNA doses were assigned to a single 2023-2024 (XBB.1.5) dose of the protein-based Novavax vaccine or the Pfizer-BioNTech mRNA vaccine, and reported symptoms on days 1, 2 and 6.

On day 1, fewer Novavax recipients reported a systemic event (62.1% vs 75.7%; risk difference -13.7 percentage points) or a local event (81.0% vs 92.7%; risk difference -11.7 points). Most events were mild, and by day 6 more than 80% reported no systemic and more than 94% no local reactions in either group.

This is useful for counselling: for a patient who found an mRNA dose unpleasant or is hesitant because of reactogenicity, the protein-based option is a reasonable, better-tolerated alternative. The trial measured side effects, not protection, so it does not speak to comparative effectiveness.

• Novavax caused fewer day-1 systemic events than Pfizer-BioNTech (62.1% vs 75.7%).
• Local reactions were also fewer with Novavax (81.0% vs 92.7%).
• Most reactions were mild and largely resolved by one week in both groups.
• Offer the protein-based vaccine to patients deterred by mRNA reactogenicity.
• This compared side effects only, not how well each vaccine protects.

Why it matters

Reactogenicity is a common reason patients decline boosters, so a better-tolerated option can support uptake.

Don't overread it

This is a reactogenicity comparison only; it does not establish which vaccine prevents more disease.

The statistics, in plain English

A risk difference of -13.7 points means about 14 fewer systemic reactions per 100 people with Novavax; the confidence interval staying below zero makes the difference statistically reliable, though it says nothing about protection.

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