A vaccine against respiratory syncytial virus (RSV) for pregnant women, developed by GSK, has proven effective in protecting babies from severe forms of this infection, but has caused an increased risk of premature birth, a side effect that has not yet been reported. could be explained. The results of the study, stopped for this reason, have been published in the scientific journal The New England Journal of Medicine, where its authors indicate that “enrollment was stopped prematurely due to safety concerns.”
The trial revealed that the vaccine based on the RSV F prefusion protein (RSVPreF3-Mat) showed an efficacy of 65.5% and 69% in preventing severe diseases of the lower respiratory tract associated with RSV in newborns up to six months of age. age. These results have been presented by Dr. Philip Dormitzer of GSK in Waltham, Massachusetts, and his team.
Despite these good results, the trial was stopped in February 2022 after a 37% increase in the risk of premature birth was detected among women who received the vaccine. In concrete numbers, 6.8% of babies born to vaccinated mothers were born prematurely, compared to 4.9% in the placebo group. This means that for every 54 babies born to vaccinated women, one additional premature birth was recorded.
The researchers, however, did not observe any other red flags regarding the safety of the vaccine in either the children or the mothers participating in the study. Even previous data from a phase II and unpublished data from a phase III showed no association between the vaccine and premature births.
The research team also examined the effects of other vaccines administered during pregnancy, such as those for COVID, flu, tetanus, and diphtheria-tetanus, which have not been linked to an increased risk of preterm birth. Interestingly, receiving additional vaccines during pregnancy was associated with a lower incidence of preterm birth in both the vaccinated and placebo groups, although the risk reduction was greater in the placebo group.
Balance between benefits and possible risks of maternal vaccination
In Spain, only Pfizer’s Abrysvo bivalent RSV vaccine is approved and recommended for use during pregnancy to protect newborns from serious RSV-related outcomes, which is funded by the National Health System for pregnant women. However, in the United States, the FDA has limited its use to between 32 and 36 weeks of gestation due to concerns about the risk of premature birth.
With more maternal vaccines in development, experts stress the importance of maintaining a balance between the benefits and potential risks of maternal vaccination to protect infants from the severe effects of infectious diseases.
The study in question, known as GRACE or RSV MAT-009, was a double-blind Phase III trial that enrolled 5,328 pregnant women ages 18 to 49 in 24 countries, randomly assigning them to receive the RSV vaccine or a placebo between weeks 24 and 34 of gestation.
The vaccine showed an efficacy of 65.5% and 69% in preventing severe lower respiratory tract diseases associated with RSV in newborns up to six months of age.
Most participants were between 18 and 34 years old, with a diverse range of ethnicities and socioeconomic levels. At 43 days after birth, data were available for 3,494 babies in the vaccine group and 1,739 in the placebo group. The research also highlighted an increased risk of very preterm births in the vaccine group, which likely contributed to a slight increase in neonatal deaths in this group.
In subsequent analyses, the researchers attempted to identify how the vaccine may have led to an increased risk of preterm birth, although the mechanisms behind this phenomenon remain unknown. This study highlights the complexity of developing safe and effective maternal vaccines, especially in low- and middle-income countries, where the need for such interventions is most critical.
Ángel Hernández Merino, pediatrician and collaborator of the Vaccine Advisory Committee, the Spanish Association of Pediatrics and the Spanish Association of Primary Care Pediatrics, who has not participated in the trial, explained in statements to SMC Spain: “Among the results , two stand out. On the one hand, a vaccine efficacy of 65.5% (37.5-82) to prevent lower respiratory tract events of any type associated with RSV, and 69% (33-87.6) for severe events, which which is a good or moderately good efficacy, which may be more or less relevant in real life depending on other variables.”
“On the other hand, the greater risk of premature births stands out in the group of newborns of vaccinated mothers, compared to those of mothers in the placebo group: RR 1.37 (1.08-1.74), one case in excess for every 54 births in the group of vaccinated mothers. On this issue, another very important fact: the highest risk of prematurity was observed, in particular, in the study centers located in countries with medium and low resources. When this issue was examined by gestational age, it was seen that very premature infants (28-32 weeks) and extremely premature infants (<28 weeks) maintained the highest risk in the group of vaccinated mothers. It remains to reveal the possible mechanism(s) that associate this vaccination with the risk of prematurity and to find out what other external factors could have contributed.”
“It cannot be overlooked that prematurity in countries with medium and low resources is a condition of very high risk for the health of newborns. It so happens that 50% of the mothers recruited for the study at the time the trial was suspended came from countries with medium/low resources, and it seems evident that this fact has conditioned the visibility of the greater risk of prematurity (of “Having middle/low-resource countries had less representation among the participants, perhaps this effect on the risk of prematurity would have gone unnoticed or had less impact,” concludes the expert.
