Safety and Immunogenicity of a Respiratory Syncytial Virus Fusion (F) Protein Nanoparticle Vaccine in Healthy Third-Trimester Pregnant Women and Their Infants

Abstract

Background Respiratory syncytial virus (RSV) is the leading cause of infant lower respiratory tract disease and hospitalization worldwide. Methods Safety and immunogenicity of RSV fusion (F) protein nanoparticle vaccine or placebo were evaluated in 50 healthy third-trimester pregnant women. Assessments included vaccine tolerability and safety in women and infants, and RSV-specific antibody measures in women before and after vaccination, at delivery and post partum. Results The vaccine was well tolerated; no meaningful differences in pregnancy or infant outcomes were observed between study groups. RSV-specific antibody levels increased significantly among vaccine recipients, including responses competitive with well-described monoclonal antibodies specific for multiple RSV neutralizing epitopes. No significant antibody increase was seen among placebo recipients, although a shallow upward trend across the RSV season was noted. Transplacental antibody transfer was 90%–120% across assays for infants of vaccinated women. Women with an interval of ≥30 days between vaccination and delivery demonstrated higher placental antibody transfer rates than women with an interval <30 days. Half-lives of RSV-specific antibodies in infants approximated 40 days. There was no evidence of severe RSV disease in infants of vaccinated mothers. Conclusions Data from this phase 2 study support a maternal immunization strategy to protect infants from RSV disease. Clinical Trials Registration NCT02247726.

Respiratory syncytial virus

“…Lastly, an aluminum-adjuvanted RSV F-protein nanoparticle vaccine (Novavax, Inc., Gaithersburg, Maryland, US) was evaluated in women of childbearing age [59] and in a phase II study in pregnant women prior to being the first vaccine evaluated in a phase III clinical trial, seeking an indication for administration in pregnancy. The phase II study demonstrated that the vaccine was safe and well tolerated, and induced significantly higher concentrations of both anti F-IgG, but also neutralizing antibodies and Palivizumab competing antibodies [60]. This study also found that maternal antibody responses peaked at 14 days after vaccination, and that an interval of ≥30 days from maternal vaccination to delivery maximized transplacental antibody transfer for all measured antibodies [60].…”

“…The phase II study demonstrated that the vaccine was safe and well tolerated, and induced significantly higher concentrations of both anti F-IgG, but also neutralizing antibodies and Palivizumab competing antibodies [60]. This study also found that maternal antibody responses peaked at 14 days after vaccination, and that an interval of ≥30 days from maternal vaccination to delivery maximized transplacental antibody transfer for all measured antibodies [60]. This study allowed the progression to a global phase III efficacy clinical trial to evaluate this maternal vaccine for the protection of RSV in infants.…”

Global Perspectives on Immunization During Pregnancy and Priorities for Future Research and Development: An International Consensus Statement

“…Studies on RSV-F protein in pregnant women have shown that these vaccines are safe and immunogenic in pregnant women (219,220). The use of these RSV vaccines in healthy pregnant women is further supported by evidence that maternal RSV neutralizing antibodies are efficiently transferred from the mother to the newborn, with levels at delivery that are similar or higher in the cord blood compared with the maternal blood at delivery (219,220).…”

Obstetrics risk Assessment: Evaluation of selection criteria for vaccine research studies in pregnant women

“…The Global Alignment of Immunization Safety Assessment in Pregnancy (GAIA) project was established, and since 2014, GAIA [3], utilizing Brighton Collaboration methodology, has developed and published case definitions and guidelines for data collection, analysis, and presentation of maternal immunization safety data in trials involving pregnant women for twenty-one obstetric and neonatal terms [4]. These case definitions and tools have been adopted in recent maternal immunization studies to evaluate maternal and neonatal outcomes, including use in a recent Phase III maternal immunization trial [5,6].…”