medwireNews: Vaccinating women against respiratory syncytial virus (RSV) during pregnancy may protect their infants from lower respiratory tract disease between birth and 6 months of age, indicate the results of a phase 3 trial.
However, the RSV prefusion F protein–based maternal (RSVPreF3-Mat) vaccine may also increase the risk for premature birth compared with placebo and further efficacy and safety data are needed, report the researchers.
“The findings regarding preterm birth led to the cessation of recruitment and vaccination in the current trial and to the discontinuation of RSVPreF3-Mat development,” write Ilse Dieussaert, from GSK – the vaccine’s developers – in Wavre, Belgium, and colleagues in The New England Journal of Medicine.
“The mechanism by which RSVPreF3-Mat may have led to an increased risk of preterm birth as compared with placebo is unknown,” they add.
The team began enrolling trial participants in 2020, including 5328 pregnant women from 24 countries who were aged between 18 and 49 years, and who were randomly assigned to receive one intramuscular injection of 120 μg RSVPreF3-Mat (n=3557) or placebo (n=1771).
Just over half of the women in each trial group (50.8% of the vaccine and 50.7% of the placebo group) were recruited from low- or middle-income countries including Argentina, Brazil, India, and the Philippines. Recruitment stopped in 2022 after the “safety signal” of preterm birth was observed by an independent data monitoring committee.
A total of 3426 infants from the vaccination group and 1711 from the placebo group were followed-up from birth until 6 months. Dieussaert and colleagues observed lower incidence rates of any medically assessed RSV-associated lower respiratory tract disease in infants whose mothers received RSVPreF3-Mat compared with placebo, at 16 versus 24, giving a vaccine efficacy of 65.5%.
Similarly, fewer infants whose mothers received the vaccine experienced severe medically assessed RSV-associated lower respiratory tract disease compared with their counterparts whose mothers received placebo, at 8 versus 14, with a vaccine efficacy of 69.0%.
An interim safety assessment at day 43 after birth revealed that a significantly higher percentage of women who received the vaccine had experienced premature preterm rupture of membranes, preterm labor, or provider-initiated preterm birth, compared with those who had received placebo, at 6.8 % versus 4.9% (relative risk = 1.37).
This imbalance in preterm birth rates between the two groups – which caused trial enrollment to halt – was mainly seen in low- and middle-income countries “where the medical need for maternal RSV vaccines is the greatest,” remarks the research team.
The preterm incidence rates for low- and middle-income countries were 9.8% versus 3.7% for high-income countries in the vaccine group, and 6.3% versus 3.6% respectively, in the placebo group.
In terms of other safety outcomes, Dieussaert et al report no difference in the incidence of neonatal death between the vaccine and placebo groups (0.4% vs 0.2%).
“The intervals from vaccination to preterm delivery generally ranged from weeks to months, which suggests the absence of a direct effect of vaccination on mechanisms that initiated preterm birth,” conclude the researchers.
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N Engl J Med 2024; 390: 1009–1021