462. Infant antibody titers at birth following maternal COVID-19 vaccination and protection against infection in the first 6 months of life
Authors: Cardemil Cristina , Munoz Flor M , Cao Yi , Gao Fei , Posavad Christine M , Badell Martina L , Bunge Katherine E , Mulligan Mark J , Parameswaran Lalitha , Olson-Chen Courtney , Novak Richard M , Brady Rebecca C , DeFranco Emily A , Gerber Jeffrey S , Pasetti Marcela , Shriver Mallory C , Coler Rhea , Berube Bryan J , Richardson Barbra A , Beigi Richard H , Neuzil Kathy M , Brown Elizabeth R 
Published: November 2023

Abstract

Background
Maternal vaccination is a promising strategy to prevent COVID-19 in early infancy, yet the amount of protection that maternally derived vaccine specific SARS-CoV-2 binding and neutralizing antibodies provide to infants in the first six months of life is not well characterized.

Methods
Infants born to mothers vaccinated during pregnancy with 2 or 3 doses of an mRNA COVID-19 vaccine (primary series or boosted group, respectively) were followed prospectively from birth up to 6 months. At delivery, anti-Spike IgG and pseudovirus neutralizing antibody (Nab) levels were measured. Between September 2021 and December 2022, at pre-specified timepoints, COVID-19 infection was determined by verified maternal report. The risk reduction for COVID-19 in infants by antibody titers at delivery was estimated using a calendar-time Cox regression model after adjusting for maternal age, booster status, and recency of last dose. The relative vaccine effectiveness (VE) of 3 vs 2 maternal vaccine doses for COVID-19 in infants &lt; 6 months was estimated in separate models.

Results
Infants in the boosted group (n=181) had higher anti-Spike IgG and pseudovirus Nab titers at delivery compared with the primary series group (n=260) (mean 4443 vs 1091 BAU/ml and 1567 vs 404 IC50, respectively; both p&lt; 0.001). A 10-fold increase in anti-Spike IgG measured at delivery was associated with a 69.2% (95% CI: 38.1%, 84.6%, p=0.001) reduction in the infant’s risk of acquiring COVID-19 in the first 6 months. Similarly, having a pseudovirus Nab response above an IC50 of 20 at delivery was associated with a 96.2% (95% CI: 75.1%, 99.4%; p=0.001) reduction in the infant’s risk of acquiring COVID-19 in the first 6 months. The relative VE of 3 vs 2 doses against infant COVID-19 was 65% (95% CI: 24%, 84%) when accounting for changes in anti-Spike IgG levels, and 83% (95% CI: 43%, 95%) when accounting for pseudovirus Nab levels.

Conclusion
Higher SARS-CoV-2 IgG Spike and pseudovirus Nab titers at delivery are associated with a substantially reduced risk of COVID-19 infection for infants in the first 6 months of life. Until infants are age-eligible for COVID-19 vaccination, maternal vaccination provides transplacentally transferred passive binding and neutralizing SARS-CoV-2 antibodies that protect against infection during early infancy.

Disclosures
Flor M. Munoz, MD, MSc, CDC respiratory virus surveillance: Grant/Research Support|Gilead: Grant/Research Support|Moderna, sanofi, aztra zeneca, Merck, GSK: Advisor/Consultant|NIH: DSMB|NIH COVID-19 vaccines in pregnancy: Grant/Research Support|Pfizer Pediatric COVID-19 vaccines: Grant/Research Support|Pfizer, Dynavax, Monderna, Meissa, NIH: DSMB Mark J. Mulligan, M.D., Lilly: Grant/Research Support|Meissa Vaccines, Inc.: Advisor/Consultant|Meissa Vaccines, Inc.: Board Member|Merck: Advisor/Consultant|Merck: Board Member|Pfizer: Advisor/Consultant|Pfizer: Board Member|Pfizer: Grant/Research Support|Sanofi: Grant/Research Support Lalitha Parameswaran, MD, MPH, Pfizer: Grant/Research Support Richard M. Novak, MD, Moderna: Advisor/Consultant Rebecca C. Brady, MD, AztraZeneca: Grant/Research Support|PATH: Grant/Research Support|Pfizer: Grant/Research Support Bryan J. Berube, PhD, HDT Bio Corp.: Author on patents|HDT Bio Corp.: Salary|HDT Bio Corp.: Ownership Interest Barbra A. Richardson, PhD, Gilead Sciences: Advisor/Consultant Kathy M. Neuzil, MD, MPH, NIH: Grant/Research Support|Pfizer: Grant/Research Support Elizabeth R. Brown, ScD, Merck: Advisor/Consultant