Administered during the last trimester of pregnancy, a bivalent respiratory syncytial virus (RSV) prefusion F protein–based (RSVpreF) vaccine reduced medically attended severe RSV-associated lower respiratory tract illness in infants, report researchers in the MATISSE trial, and had a favorable safety profile. “Vaccination offers the possibility of an immune response to multiple neutralizing epitopes, thus reducing the risk of immune escape observed with some monoclonal antibodies,” write the authors. “Passive transfer of maternal antibodies can protect the youngest and most vulnerable infants immediately after birth, before effective immune responses can be elicited from active vaccination in infants.”
The worldwide phase 3 trial included pregnant women at 24 through 36 weeks’ gestation who received a single dose of intramuscular bivalent RSVpreF vaccine 120 μg or placebo. The primary efficacy endpoints were medically attended severe RSV-associated lower respiratory tract illness and medically attended RSV-associated lower respiratory tract illness in infants within 90, 120, 150, and 180 days after birth.
“At this prespecified interim analysis, the success criterion for vaccine efficacy was met with respect to one primary end point. Overall, 3,682 maternal participants received vaccine and 3,676 received placebo; 3,570 and 3,558 infants, respectively, were evaluated. Medically attended severe lower respiratory tract illness occurred within 90 days after birth in 6 infants of women in the vaccine group and 33 infants of women in the placebo group (vaccine efficacy, 81.8%; 99.5% CI, 40.6 to 96.3); 19 cases and 62 cases, respectively, occurred within 180 days after birth (vaccine efficacy, 69.4%; 97.58% CI, 44.3 to 84.1). Medically attended RSV-associated lower respiratory tract illness occurred within 90 days after birth in 24 infants of women in the vaccine group and 56 infants of women in the placebo group (vaccine efficacy, 57.1%; 99.5% CI, 14.7 to 79.8); these results did not meet the statistical success criterion. No safety signals were detected in maternal participants or in infants and toddlers up to 24 months of age. The incidences of adverse events reported within 1 month after injection or within 1 month after birth were similar in the vaccine group (13.8% of women and 37.1% of infants) and the placebo group (13.1% and 34.5%, respectively).”
Editorial: “In high-income countries, complex policy decisions about whether to offer maternal immunization with RSV preF vaccine or a long-acting RSV monoclonal antibody in infants will be required,” writes an editorialist. “In the United States, substantial efforts would be needed to increase the percentage of pregnant women who receive the RSVpreF vaccine above the 57 to 61% reported for influenza and tetanus–diphtheria–acellular pertussis vaccines. If both the RSVpreF vaccine for pregnant women and RSV monoclonal antibodies for infants are available, enhanced communication between obstetrical and pediatric care providers will be necessary to ensure appropriate use of each product. Doubly protecting healthy term infants with the use of RSVpreF vaccine antenatally and an RSV monoclonal antibody postnatally while leaving many of the infants in the world unimmunized would waste valuable products and exacerbate worldwide inequities in child health.”