Author ORCID Identifier

https://orcid.org/0000-0001-9839-8448

Date of Award

Winter 2-5-2026

Document Type

Thesis (Ph.D.)

Department or Program

Microbiology and Immunology

First Advisor

DR. MARGARET E. ACKERMAN

Abstract

Pregnancy represents a distinct immunological state characterized by the necessity to maintain maternal tolerance toward the semi-allogeneic fetus while preserving effective antimicrobial defenses. This altered immune milieu profoundly influences vaccine responsiveness and disease susceptibility, making the evaluation of vaccine-induced immunity during gestation critical for maternal and neonatal protection. To delineate how gestational immune adaptation modulates humoral immunity, longitudinal analyses were conducted in pregnant and age-matched non-pregnant controls following SARS-CoV-2 mRNA and inactivated influenza A (H1N1) vaccination. We conducted a longitudinal study comparing SARS-CoV-2 mRNA vaccine responses in pregnant and non-pregnant women. Pregnant participants showed modestly reduced humoral and effector responses, while prior infection enhanced immunogenicity. Vaccine-induced antibodies efficiently crossed the placenta, providing passive neonatal protection. Spike-specific IgG4 rose after the two-dose series regardless of pregnancy status, with IgG4 clonotypes originating early and persisting over time. These clonotypes were enriched in maternal but not cord blood, reflecting limited placental transfer. Findings reveal pregnancy-associated modulation of immune kinetics yet preservation of delayed IgG4 class switching, highlighting maternal vaccination’s dual protection for mother and fetus. In parallel, evaluation of pregnant and non-pregnant women immunized with an unadjuvanted inactivated influenza A (H1N1) vaccine (NCT00992719) during the 2009 pandemic demonstrated that vaccination was well tolerated and immunogenic. However, pregnant women receiving the standard 15 µg dose exhibited fewer increases in antibody magnitude and effector diversity compared with non-pregnant controls. Doubling the antigen dose to 30 µg enhanced hemagglutinin- and neuraminidase-specific responses, promoted durable Fc effector functions such as antibody-dependent cellular cytotoxicity, phagocytosis, and complement deposition, and improved placental antibody transfer.

Collectively, these findings reveal that pregnancy modulates the magnitude, kinetics, and subclass distribution of vaccine-induced humoral immunity in a platform- and dose-dependent manner. The results underscore maternal immunization as an essential public health strategy conferring dual maternal-fetal protection, while offering mechanistic insight into how pregnancy shapes vaccine-induced immune architecture and durability.

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Available for download on Saturday, February 05, 2028

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