RSV and Covid-19 vaccines together: reassuring results, but one immune-response criterion missed

Two vaccines on the same day or about a month apart

This phase 3, multicenter, open-label trial included 833 vaccinated participants. Randomization assigned 417 people to simultaneous administration and 416 to sequential administration, about a month apart.

The researchers studied an RSV vaccine based on the prefusion F protein with the AS01E adjuvant, paired with a messenger RNA Covid-19 vaccine targeting Omicron XBB.1.5. The findings apply to this specific combination, not automatically to all vaccine formulations.

The primary endpoint assessed neutralizing antibodies one month after vaccination. Reactogenicity was assessed over the following four days, and safety for up to six months.

The threshold was met for RSV, narrowly missed for Covid-19

The trial sought to establish that simultaneous administration did not reduce immune responses beyond a predefined margin. To meet this criterion, the upper bound of the 95% confidence interval for the geometric mean titer ratio, sequential group divided by simultaneous group, had to be less than or equal to 1.50.

This condition was met for both RSV subtypes studied, RSV-A and RSV-B. For SARS-CoV-2 Omicron XBB.1.5, the ratio was 1.31, with a confidence interval of 1.13 to 1.51. The upper bound therefore slightly exceeded the threshold.

The authors consider that this difference does not suggest clinically relevant interference. However, this interpretation does not demonstrate equivalent protection against infections or hospitalizations: the primary endpoint measured antibodies, not these clinical outcomes.

Broadly comparable tolerability in this trial

The most common solicited reactions were injection-site pain, muscle pain and fatigue. Most were mild to moderate in intensity. Their overall median duration was three days or less and was comparable between groups.

Unsolicited adverse events and serious adverse events were broadly balanced between groups, according to the abstract. However, it does not provide their detailed frequencies. These data cannot rule out rare adverse effects.

What we can take away

The trial provides support for simultaneous administration of the two formulations studied, with a specific caveat regarding the response to SARS-CoV-2. It does not demonstrate identical clinical protection and does not, on its own, constitute a vaccination recommendation applicable in France.