2079. Maternal hybrid immunity to SARS-CoV-2 during pregnancy provides more durable infant antibody responses compared to natural infection alone
Authors: LaCourse Sylvia M , Wetzler Erica A , Aurelio Morgan C , Escudero Jaclyn N , Selke Stacy , Greninger Alex L , Goecker Erin , Barnes Sarina R , Arnould Isabel S , Pérez-Osorio Ailyn C , Kachikis Alisa B , Englund Janet A , Drake Alison L 
Published: November 2023

Abstract

Background
Immunity from natural infection and vaccination (hybrid) may provide more durable SARS-CoV-2 antibody responses; whether this increases durability of maternally-derived antibody responses in infants is unknown.

Methods
Participants with prior SARS-CoV-2 infection in pregnancy (anti-nucleocapsid [anti-N] IgG+ on enrollment or prior RT-PCR+ or antigen+) were enrolled between January 2021-August 2022. Blood samples collected in pregnancy, delivery/birth, 0-&lt; 3 and 3-6 months postpartum were tested for anti-S+ IgG by Abbott Architect (positive: ≥50 AU/mL) and neutralizing antibodies (serum dilution inhibited infection by 50% [ND50 heat] ≥20 and R2 ≥0.9).

Results
Among 107 participants at enrollment in pregnancy, median age was 32 years (IQR 30-35) and median gestational age was 31 weeks (IQR 19.1–37.9). At delivery (median 19.7 weeks [IQR 14.3-30.0] from SARS CoV-2 diagnosis), unvaccinated participants and their infants were less likely to have anti-S IgG+ (maternal 87%; cord 86%) or neutralizing antibodies (maternal 86%; cord 75%) than vaccinated (≥1 dose) participants and their infants (maternal and cord both 100% anti-S IgG+ and neutralizing antibodies) (all p≤0.01). By 6 months of age, the proportion of infants of mothers who remained unvaccinated at birth with anti-S IgG+ and neutralizing antibody declined to 50% and 14% (anti-S IgG+ and neutralizing antibody, respectively) compared to 100% (anti-S IgG+ and neutralizing antibody) among infants with vaccinated mothers (all p&lt; 0.01).
Infants with anti-S IgG+ or neutralizing antibodies born to unvaccinated mothers had lower median antibody levels at birth (anti-S IgG log10 2.95 vs. 4.40 AU/ml; neutralization log10 1:2.37 vs. 1:4.00, all p&lt; 0.01) and through 6 months of age (anti-S IgG log10 1.95 vs. 3.84 AU/ml, p&lt; 0.01; log10 neutralization 1:1.34 vs. 1:3.20, p=0.11) vs. infants with mothers vaccinated prior to delivery.
Neutralizing antibody responses among A) pregnant people with prior SARS-CoV-2 infection during pregnancy and B) their infants by maternal vaccination status *†
*Among participants and their infants with positive neutralizing antibodies (ND50 heat ≥20 and R2 ≥0.9). †Maternal vaccination status is at time of blood sample collection; for infants refers to maternal vaccination status at time of delivery.

Conclusion
SARS-CoV-2 infection alone during pregnancy did not provide persistent antibody responses in infants through 6 months of age. Maternal vaccination provided more durable antibody responses in participants with prior SARS-CoV-2, potentially providing protection to vulnerable infants in the months prior to their own COVID-19 vaccine eligibility.

Disclosures
Sylvia M. LaCourse, MD, MPH, Merck: Grant/Research Support Alex L. Greninger, MD, PhD, MS, MPhil, Abbott Diagnostics: central testing|Cepheid: central testing|Hologic Inc: central testing|Janssen Infectious Disease: central testing|Novavax, Inc.: central testing|Pfizer, Inc.: central testing Alisa B. Kachikis, MD, MSc, Merck: Grant/Research Support|Pfizer: Grant/Research Support Janet A. Englund, MD, Ark Biopharma: Advisor/Consultant|AstraZeneca: Advisor/Consultant|AstraZeneca: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Meissa Vaccines: Advisor/Consultant|Merck: Grant/Research Support|Moderna: Advisor/Consultant|Moderna: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Sanofi Pasteur: Advisor/Consultant Alison L. Drake, PhD, MPH, Merck: Grant/Research Support