Dissecting Fc signatures of protection in neonates following maternal influenza vaccination in a placebo-controlled trial

• Published in: Cell reports (Cambridge) 2022-02, Vol.38 (6), p.110337-110337, Article 110337
• Main Authors: Boudreau, Carolyn M., Burke, John S., Shuey, Kiel D., Wolf, Caitlin, Katz, Joanne, Tielsch, James, Khatry, Subarna, LeClerq, Steven C., Englund, Janet A., Chu, Helen Y., Alter, Galit
• Format: Article
• Language: English
• Subjects: adaptive immunity; Antibodies, Viral - immunology; antibody; Fc effector function; Fc receptor; Female; Humans; Infant; Infant, Newborn; influenza; Influenza Vaccines - immunology; Influenza, Human - immunology; Influenza, Human - prevention & control; innate immunity; maternal vaccination; Placebos; placental transfer; Pregnancy; vaccination; Vaccination - methods
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2022.110337

Influenza is an important cause of illness and morbidity for infants. Seasonal influenza vaccination during pregnancy aims to provide protection to mothers, but it can also provide immunity to infants. The precise influence of maternal vaccination on immunity in infants and how vaccine-elicited antibodies provide protection in some but not all infants is incompletely understood. We comprehensively profiled the transfer of functional antibodies and defined humoral factors contributing to immunity against influenza in a clinical trial of maternal influenza vaccination. Influenza-specific antibody subclass levels, Fc ɣ receptor (FCGR) binding levels, and antibody-dependent innate immune functions were all profiled in the mothers during pregnancy and at birth, as well as in cord blood. Vaccination increased influenza-specific antibody levels, antibody binding to FCGR, and specific antibody-dependent innate immune functions in both maternal and cord blood, with FCGR binding most enhanced via vaccination. Influenza-specific FCGR binding levels were lower in cord blood of infants who subsequently developed influenza infection. Collectively these data suggest that in addition to increased antibody amounts, the selective transfer of FCGR-binding antibodies contributes to the protective immune response in infants against influenza. [Display omitted] •Maternal influenza vaccination induces innate immune-functional antibodies•These antibodies are transferred across the placenta to the developing fetus•Antibodies that bind Fc γ receptors protect infants from influenza•Maternal vaccination induces antibody qualities linked to protection in infants Boudreau et al. characterize the antibodies induced by influenza vaccination during pregnancy and describe which of these antibodies are transferred to the infant. They show that the antibodies arising after vaccination provide protection from influenza to infants during the first months of life.