Maternal influenza vaccination elicits transplacental transfer of hemagglutinin stem-specific IgG

Abstract

Hemagglutinin (HA) glycoprotein is the dominant antigen of current influenza vaccines and antigenic drift requires a seasonal vaccine. The stem region of HA is conserved and is therefore a promising target for a universal vaccine. Understanding HA stem specific response is crucial in universal vaccine development. We hypothesize that maternal vaccination with influenza vaccine would result in a boost of HA stem antibodies and higher concentrations in neonatal cord blood. Two parallel prospective cohorts of pregnant women were recruited mid-trimester before influenza vaccination (n=15) and 3rd trimester after vaccination (n=18). Maternal plasma antibodies were assessed for 15 participants pre and post 2019 seasonal influenza vaccine and for 18 prenatally vaccinated participants with paired neonatal cord blood samples. Enzyme linked immunosorbent assay (ELISA) detected IgG and IgG subclass titers specific for vaccine antigens and for recombinant HA stem antigen. We used Wilcoxon signed rank test to assess antibody titer differences between pre and post vaccine and maternal and umbilical cord plasma. HA stem specific IgG titers were boosted post vaccination (log2 threshold titer 14.5, (95% CI 13.8-15.2) pre versus (v) 16.0 (95% CI 15.2-16.8) post-vaccine, P = 0.004) more robustly than IgG to all vaccine antigens (18.6 pre v 19.4 post-vaccine, P = 0.008). Maternal plasma post-vaccine HA stem titers were higher for IgG1 (9.0 v 7.7, P = 0.001) and IgG3 (8.2 v 7.1, P = 0.004) subclasses compared to other subclasses. While IgG vaccine titers were similar in neonatal cord blood and maternal plasma (P = 0.09), IgG specific for stem concentrated in cord blood (16.0 v 15.4, P = 0.002) which was dominated by IgG1 subclass (10.1 v 9.6, P = 0.004). Maternal influenza vaccination generates IgG response specific to HA stem antigen. This response is IgG1 and IgG3 subclass dominant. HA stem cord blood IgG titers were higher than maternal titers and were IgG1 dominant in this cohort. These data support HA stem as a promising antigen target for future universal maternal vaccination.View Large Image Figure ViewerDownload Hi-res image Download (PPT)