RSV vaccinne

The short version: the RSV vaccines for older adults show a clear efficacy signal, but the safety data carries a real signal of Guillain-Barré syndrome, and the maternal vaccine carries a preterm birth imbalance that the manufacturer's own trial could not rule out.

The evidence for the three approved vaccines for adults 60 and older comes from manufacturer-funded phase 3 trials. Arexvy (GSK) showed about 83% efficacy against RSV lower respiratory tract disease in the first season, dropping to about 63% cumulative over three seasons [2]. Abrysvo (Pfizer) showed efficacy in a similar range, and mRESVIA (Moderna) showed about 84% efficacy against disease with three or more symptoms [2]. These are real reductions in symptomatic illness, measured against placebo.

But the safety picture is not clean. A national study in England found that among adults 74-79 who received the bivalent RSV pre-F vaccine (Abrysvo), the risk of Guillain-Barré syndrome in the six weeks after vaccination was about 3.3 times higher than in the same individuals' later person-time [3]. That translates to roughly 23 attributable cases per million doses in the primary analysis, and about 34 per million in a broader six-month analysis [3]. The authors judged the benefit still outweighed the risk, but that is a judgment, not a fact. The GBS signal is real and the confidence intervals are wide.

For the maternal vaccine (Abrysvo, given during pregnancy to protect infants), the MATISSE trial found about 82% efficacy against severe RSV illness in infants in the first 90 days, dropping to about 69% by 180 days [1, 4]. But the same trial found a numerical imbalance in preterm births: 5.7% in the vaccinated group versus 4.7% in the placebo group [5]. The FDA noted that the data were insufficient to establish or exclude a causal relationship [5]. A separate GSK maternal vaccine trial was terminated early because of higher preterm birth rates (6.8% vs 4.9%) and a numerical imbalance in infant deaths (0.4% vs 0.2%) [4]. That is a different vaccine, but it shows the class can carry this risk.

The long-term safety data is thin. The trials followed patients for one to three seasons, not for years. The GBS signal was detected only through active national surveillance, not through the trials themselves. The maternal preterm birth imbalance was visible in the trial but the manufacturer's own FDA submission could not rule it out. The burden of proof has not been met for long-term safety in any population.

My call: for an older adult at high risk of severe RSV (advanced age, lung disease, frailty), the benefit likely outweighs the known GBS risk, but that risk is real and should be disclosed. For a healthy pregnant woman, the preterm birth signal is enough to demand a much larger safety trial before routine use. Confidence: moderate for short-term efficacy in older adults, low for long-term safety in any group.