Enhanced placental antibody transfer efficiency with longer interval between maternal RSV vaccination and birth

Olyvia J Jasset; Paola Andrea Lopez Zapana; Zeynep Bahadir; Lydia Shook; Maria Dennis; Emily Gilbert; Zhaojing Ariel Liu; Rachel V Yinger; Caroline Bald; Caroline G Bradford; Alexa H Silfen; Sabra L Klein; Andrew Pekosz; Sallie Permar; Liza Konnikova; Lael M Yonker; Douglas Lauffenburger; Ashley Nelson; Michal A Elovitz; Andrea G Edlow

doi:10.1016/j.ajog.2024.10.053

Enhanced placental antibody transfer efficiency with longer interval between maternal RSV vaccination and birth

Am J Obstet Gynecol. 2024 Nov 6:S0002-9378(24)01125-6. doi: 10.1016/j.ajog.2024.10.053. Online ahead of print.

Authors

Olyvia J Jasset¹, Paola Andrea Lopez Zapana², Zeynep Bahadir³, Lydia Shook⁴, Maria Dennis³, Emily Gilbert¹, Zhaojing Ariel Liu¹, Rachel V Yinger¹, Caroline Bald¹, Caroline G Bradford¹, Alexa H Silfen¹, Sabra L Klein⁵, Andrew Pekosz⁵, Sallie Permar³, Liza Konnikova⁶, Lael M Yonker⁷, Douglas Lauffenburger⁸, Ashley Nelson³, Michal A Elovitz⁹, Andrea G Edlow¹⁰

Affiliations

¹ Massachusetts General Hospital, Vincent Center for Reproductive Biology, Boston, MA, USA.
² Massachusetts General Hospital, Vincent Center for Reproductive Biology, Boston, MA, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
³ Department of Pediatrics, Weill Cornell Medicine, New York, NY, USA.
⁴ Massachusetts General Hospital, Vincent Center for Reproductive Biology, Boston, MA, USA; Massachusetts General Hospital, Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
⁵ W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
⁶ Departments of Pediatrics, Immunobiology, and Obstetrics, Gynecology and Reproductive Sciences, Yale University, New Haven, CT.
⁷ Massachusetts General Hospital, Department of Pediatrics, Boston, MA, USA.
⁸ Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
⁹ Women's Biomedical Research Institute, Icahn School of Medicine at Mount Sinai, New York, NY USA; Department of Obstetrics, Gynecology and Reproductive Sciences, Icahn school of Medicine at Mount Sinai, New York, NY, USA.
¹⁰ Massachusetts General Hospital, Vincent Center for Reproductive Biology, Boston, MA, USA; Massachusetts General Hospital, Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Boston, MA, USA; Harvard Medical School, Boston, MA, USA. Electronic address: aedlow@mgh.harvard.edu.

PMID: 39515450
DOI: 10.1016/j.ajog.2024.10.053

Abstract

Background: Respiratory Syncytial Virus (RSV) is associated with significant neonatal and infant morbidity and mortality. Maternal bivalent RSVpreF RSV vaccination to protect neonates and infants was approved in September 2023 for administration between 32+0 and 36+6 weeks to protect neonates and infants. This approved timeframe is narrower than the 24-36 week window evaluated in the clinical trial, due to the possible association between preterm birth and vaccine administration. Currently, data are lacking on how maternal vaccine timing within the approved window affects the transfer of antibodies from mother to fetus, critical information that could influence clinical practice.

Objectives: We sought to examine how gestational age at vaccination and time elapsed from maternal RSV vaccination to delivery impacted transfer of maternal antibodies measured in the umbilical cord at delivery and in peripheral blood of 2-month infants. We also examined differences in maternal and cord RSV antibody levels achieved by vaccination versus natural RSV infection.

Study design: A prospective cohort study was conducted at two academic medical centers between September 20, 2023 and March 21, 2024, enrolling 124 individuals who received the RSV vaccine during pregnancy. Infant capillary blood was collected at 2 months of age from 29 of the infants. Maternal and cord IgG levels achieved by RSV vaccination were compared to those associated with maternal natural RSV infection, using banked blood from 20 maternal:cord dyads collected prior to the availability of the maternal RSV vaccine. Levels of IgG against RSV strain A2 and B fusion (F) and attachment (G) proteins and against pertussis toxin (as a comparator antigen from a vaccine routinely administered earlier in pregnancy) were measured using a Binding Antibody Multiplex Assay. Differences in titers between vaccination and natural infection were examined using Wilcoxon rank sum test. Differences in cord:maternal transfer ratios and 2-month infant antibody levels by timing of maternal vaccination were evaluated by Kruskal-Wallis testing.

Results: Maternal RSV vaccination resulted in significantly higher maternal and cord anti-RSV F antibody levels than natural infection (5.72 vs 4.82 log₁₀MFI, p < 0.0001 maternal; 5.81 vs 5.03 log₁₀MFI, p < 0.0001 cord). Maternal vaccination 2-3 weeks and 3-4 weeks prior to delivery was associated with significantly lower cord:maternal transfer ratios than were observed when vaccination occurred > 5 weeks prior to delivery (p = 0.03 for 2-3 weeks, p = 0.007 for 3-4 weeks), and significantly lower transfer ratios than observed for pertussis vaccination administered prior to 30 weeks' gestation (p = 0.008 for 2-3 weeks, p = 0.03 for 3-4 weeks, similar at > 4 weeks).

Conclusion: (s): Vaccine administration earlier in the approved 32-36 week window (at least 5 weeks prior to delivery) results in the highest transplacental transfer of maternal antibodies to the neonate. These results should inform the counseling of pregnant individuals on optimal vaccination timing.

Keywords: Abrysvo; Cord blood; RSV; maternal blood; neonatal immunity; transplacental transfer; vaccine.