Publications by Year: 2021

The successful development of several COVID-19 vaccines has substantially reduced morbidity and mortality in regions of the world where the vaccines have been deployed. However, in the wake of the emergence of viral variants, able to evade vaccine induced neutralizing antibodies, real world vaccine efficacy has begun to show differences across the mRNA platforms, suggesting that subtle variation in immune responses induced by the BNT162b2 and mRNA1273 vaccines may provide differential protection. Given our emerging appreciation for the importance of additional antibody functions, beyond neutralization, here we profiled the postboost binding and functional capacity of the humoral response induced by the BNT162b2 and mRNA-1273 in a cohort of hospital staff. Both vaccines induced robust humoral immune responses to WT SARS-CoV-2 and VOCs. However, differences emerged across epitopespecific responses, with higher RBD- and NTD-specific IgA, as well as functional antibodies (ADNP and ADNK) in mRNA-1273 vaccine recipients. Additionally, RBD-specific antibody depletion highlighted the different roles of non-RBD-specific antibody effector function induced across the mRNA vaccines, providing novel insights into potential differences in protective immunity generated across these vaccines in the setting of newly emerging VOCs.

OBJECTIVE: Compare the incidence of hypoglycemia in neonates born to patients with diabetes, based on last maternal glucose before delivery.

STUDY DESIGN: Cohort of singleton births from individuals with pregestational and gestational diabetes (GDM) from 2017 to 2019.

RESULTS: We included 853 deliveries. Maternal hyperglycemia before delivery was associated with 1.8-fold greater risk of neonatal hypoglycemia (glucose < 45 mg/dL) in patients with GDM on medication (adjusted risk ratio (aRR): 1.8; 95% CI: 1.1-2.7), compared with euglycemia. This association was not seen in diet-controlled GDM (0.5; 0.23-1.1), nor in Type 1 (1.1; 0.88-1.4), or Type 2 pregestational diabetes (1.1; 0.61-1.9). Further, pregestational diabetes, compared to GDM, regardless of intrapartum maternal glucose control, was associated with neonatal hypoglycemia and NICU admission.

CONCLUSION: Maternal hyperglycemia before delivery only carried a higher risk of neonatal hypoglycemia in those with GDM on medications. Other interventions to reduce neonatal hypoglycemia are needed.

Antibody transfer via breastmilk represents an evolutionary strategy to boost immunity in early life. Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibodies have been observed in the breastmilk, the functional quality of these antibodies remains unclear. Here, we apply systems serology to characterize SARS-CoV-2-specific antibodies in maternal serum and breastmilk to compare the functional characteristics of antibodies in these fluids. Distinct SARS-CoV-2-specific antibody responses are observed in the serum and breastmilk of lactating individuals previously infected with SARS-CoV-2, with a more dominant transfer of immunoglobulin A (IgA) and IgM into breastmilk. Although IgGs are present in breastmilk, they are functionally attenuated. We observe preferential transfer of antibodies capable of eliciting neutrophil phagocytosis and neutralization compared to other functions, pointing to selective transfer of certain functional antibodies to breastmilk. These data highlight the preferential transfer of SARS-CoV-2-specific IgA and IgM to breastmilk, accompanied by select IgG subpopulations, positioned to create a non-pathologic but protective barrier against coronavirus disease 2019 (COVID-19).