Abstract Title
Repertoire of naturally acquired norovirus maternal antibodies in newborns
Presenter
Verónica Costantini, Centers for Disease Control and Prevention
Co-Author(s)
Boris Relja2, Amina Rizwan3, Kimberly Huynh1, Claire P Mattison1,4, Umesh D Parashar1, Daniel C Payne1, Mary Allen Staat5,6, Ardythe L Morrow7, and Jan Vinjé1. 1Division of Viral Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA, 2CDC Foundation, Atlanta, GA, USA, 3OAK Ridge Institute for Science and Education, Oak ridge, TN, 4Cherokee Nation Operational Solutions, Tulsa, OK, 5Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, 6Division of Infectious Diseases, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, 7Department of Environmental and Public Health Sciences, University of Cincinnati College of Medicine, Cincinnati, OH, USA
Abstract
Background: Maternal IgG antibodies transferred via placenta reduce the risk of severe infections in newborns. The magnitude, specificity, and neutralizing capacity of these antibodies preventing early-life norovirus disease remain unclear.
Methods: Serum was collected from pregnant mothers (third trimester) and from children (cord blood, 6 weeks and 6, 12, 18 and 24 months of age) enrolled between April 2017 and July 2018 in the PREVAIL birth cohort study. Norovirus IgG against 5 genotypes was evaluated by EIA. Neutralizing activity against GII.4 Sydney was measured using human intestinal enteroids.
Results: Maternal IgG GMT across genotypes was 1087 (95%CI: 931.2-1269) with GMT GI.3> GII.4 Sydney >GII.6>GI.1>GII.17. Cord blood IgG GMT was 1444 (95%CI: 1177-1772) with GMT GI.3>GII.6> GII.4 Sydney>GI.1>GII.17. The IgG GMT fell to 385.2 (95%CI: 320.4-436.0) at 6 weeks, and 64.25 (95% CI: 55.57-74.29) at 6 months. Median IgG Transplacental transfer ratio (TpTr) was 1.344 (range 0.002-52.75) with TpTr GI.1>GII.17>GI.3> GII.6 >GII.4. For each genotype, 4–11% of TpTr exceeded 1SD above the genotype mean. Maternal and cord blood IgG strongly correlated (all genotypes) whereas no correlation was found between maternal IgG and TpTr. Neutralizing GII.4 antibodies (nGII.4Ab) were detected in maternal (median 97.6% neutralization; range 25.01-99.94) and cord blood (median 84.34%; range 4.53-99.96). Median TpTr for nGII.4Ab was 0.9829 (range 0.017-2.425) with 19% of the TpTr above/below 1SD from the mean.
Conclusion: Our findings provide a detailed analysis of transplacental norovirus antibody transfer and present the first data on neutralizing antibodies that likely help prevent disease in early infancy.
Methods: Serum was collected from pregnant mothers (third trimester) and from children (cord blood, 6 weeks and 6, 12, 18 and 24 months of age) enrolled between April 2017 and July 2018 in the PREVAIL birth cohort study. Norovirus IgG against 5 genotypes was evaluated by EIA. Neutralizing activity against GII.4 Sydney was measured using human intestinal enteroids.
Results: Maternal IgG GMT across genotypes was 1087 (95%CI: 931.2-1269) with GMT GI.3> GII.4 Sydney >GII.6>GI.1>GII.17. Cord blood IgG GMT was 1444 (95%CI: 1177-1772) with GMT GI.3>GII.6> GII.4 Sydney>GI.1>GII.17. The IgG GMT fell to 385.2 (95%CI: 320.4-436.0) at 6 weeks, and 64.25 (95% CI: 55.57-74.29) at 6 months. Median IgG Transplacental transfer ratio (TpTr) was 1.344 (range 0.002-52.75) with TpTr GI.1>GII.17>GI.3> GII.6 >GII.4. For each genotype, 4–11% of TpTr exceeded 1SD above the genotype mean. Maternal and cord blood IgG strongly correlated (all genotypes) whereas no correlation was found between maternal IgG and TpTr. Neutralizing GII.4 antibodies (nGII.4Ab) were detected in maternal (median 97.6% neutralization; range 25.01-99.94) and cord blood (median 84.34%; range 4.53-99.96). Median TpTr for nGII.4Ab was 0.9829 (range 0.017-2.425) with 19% of the TpTr above/below 1SD from the mean.
Conclusion: Our findings provide a detailed analysis of transplacental norovirus antibody transfer and present the first data on neutralizing antibodies that likely help prevent disease in early infancy.