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Many questions remain about the prevalence and effects of SARS-CoV-2 infection in malaria-endemic African countries like Uganda, particularly in vulnerable groups such as pregnant women. We describe SARS-CoV-2 immunoglobulin (Ig)G and IgM antibody responses and clinical outcomes in mother-infant dyads enrolled in malaria chemoprevention trials in Uganda. From December 2020-February 2022, among 400 unvaccinated pregnant women enrolled at 12-20 weeks gestation and followed through delivery, 128 (32%) were seronegative for anti-SARS-CoV-2 IgG and IgM at enrollment and delivery, 80 (20%) were infected prior to or early in pregnancy, and 192 (48%) were infected or re-infected with SARS-CoV-2 during pregnancy. We observed preferential binding of plasma IgG to Wuhan-Hu-1-like antigens in individuals seroconverting up to early 2021, and to Delta variant antigens in a subset of individuals in mid-2021. Breadth of IgG binding to all variants improved over time, consistent with affinity maturation of the antibody response in the cohort. No women experienced severe respiratory illness during the study. SARS-CoV-2 infection in early pregnancy was associated with lower median length-for-age Z-score at age 3 months compared with no infection or late pregnancy infect (-1.54 versus -0.37 and -0.51, P = 0.009). These findings suggest that pregnant Ugandan women experienced high levels of SARS-CoV-2 infection without severe respiratory illness. Variant-specific serology testing demonstrated evidence of antibody affinity maturation at the population level. Early gestational SARS-CoV-2 infection was associated with transient shorter stature in early infancy. Further research should explore the significance of this finding and define targeted measures to prevent infection in pregnancy.

During the SARS-CoV-2 pandemic, novel and traditional vaccine strategies have been deployed globally. We investigated whether antibodies stimulated by mRNA vaccination (BNT162b2), including third-dose boosting, differ from those generated by infection or adenoviral (ChAdOx1-S and Gam-COVID-Vac) or inactivated viral (BBIBP-CorV) vaccines. We analyzed human lymph nodes after infection or mRNA vaccination for correlates of serological differences. Antibody breadth against viral variants is lower after infection compared with all vaccines evaluated but improves over several months. Viral variant infection elicits variant-specific antibodies, but prior mRNA vaccination imprints serological responses toward Wuhan-Hu-1 rather than variant antigens. In contrast to disrupted germinal centers (GCs) in lymph nodes during infection, mRNA vaccination stimulates robust GCs containing vaccine mRNA and spike antigen up to 8 weeks postvaccination in some cases. SARS-CoV-2 antibody specificity, breadth, and maturation are affected by imprinting from exposure history and distinct histological and antigenic contexts in infection compared with vaccination., Competing Interests: Declaration of interests S.D.B. has consulted for Regeneron, Sanofi, Novartis, and Janssen on topics unrelated to this study and owns stock in AbCellera Biologics. K.C.N. reports grants from the National Institute of Allergy and Infectious Diseases (NIAID), Food Allergy Research & Education (FARE), End Allergies Together (EAT), National Heart Lung and Blood Institute (NHLBI), and National Institute of Environmental Health Sciences (NIEHS). K.C.N. is Director of FARE and World Allergy Organization (WAO) Center of Excellence at Stanford; Adviser at Cour Pharmaceuticals; Cofounder of Before Brands, Alladapt, Latitude, and IgGenix; National Scientific Committee member for the Immune Tolerance Network (ITN) of NIAID; recipient of a Research Sponsorship from Nestle; Consultant and Advisory Board Member at Before Brands, Alladapt, IgGenix, NHLBI, and ProBio; and Data and Safety Monitoring Board member at NHLBI. J.L.W., J.N.W., and G.B.S. are employees of Meso Scale Diagnostics (MSD)., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Different SARS-CoV-2 vaccines are approved in various countries, but few direct comparisons of the antibody responses they stimulate have been reported. We collected plasma specimens in July 2021 from 196 Mongolian participants fully vaccinated with one of four COVID-19 vaccines: Pfizer/BioNTech, AstraZeneca, Sputnik V, and Sinopharm. Functional antibody testing with a panel of nine SARS-CoV-2 viral variant receptor binding domain (RBD) proteins revealed marked differences in vaccine responses, with low antibody levels and RBD-ACE2 blocking activity stimulated by the Sinopharm and Sputnik V vaccines in comparison to the AstraZeneca or Pfizer/BioNTech vaccines. The Alpha variant caused 97% of infections in Mongolia in June and early July 2021. Individuals who recover from SARS-CoV-2 infection after vaccination achieve high antibody titers in most cases. These data suggest that public health interventions such as vaccine boosting, potentially with more potent vaccine types, may be needed to control COVID-19 in Mongolia and worldwide., Competing Interests: Declaration of interests S.D.B. has consulted for Regeneron, Sanofi, and Novartis on topics unrelated to this study and owns stock in AbCellera Biologics; B.P. and P.S.A. are inventors on a provisional patent application (no. 63/026,577) submitted by the Board of Trustees of the Leland Stanford Junior University, Stanford, CA, that covers the use of “Therapeutic Methods for Treating COVID-19 Infections”; B.P. serves on the External Immunology Network of GSK and on the Scientific Advisory Board of Medicago and Boehringer Ingelheim; and K.C.N. reports grants from National Institute of Allergy and Infectious Diseases (NIAID), Food Allergy Research & Education (FARE), End Allergies Together (EAT), National Heart, Lung, and Blood Institute (NHLBI), and National Institute of Environmental Health Sciences (NIEHS). K.C.N. is Director of FARE and World Allergy Organization (WAO) Center of Excellence at Stanford, Advisor at Cour Pharmaceuticals, Cofounder of Before Brands, Alladapt, Latitude, and IgGenix, National Scientific Committee member for the Immune Tolerance Network (ITN) of NIAID, recipient of a Research Sponsorship from Nestle, Consultant and Advisory Board Member at Before Brands, Alladapt, IgGenix, NHLBI, and ProBio, and Data and Safety Monitoring Board member at NHLBI; R.S. Chinthrajah receives grant support from CoFAR National Institute of Allergy and Infectious Diseases, Aimmune, DBV Technologies, Astellas, AnaptysBio, Novartis, and Regeneron and is an advisory board member for Alladapt Immunotherapeutics Inc., Novartis, and Genentech. J.L.W., J.N.W., and G.B.S. are employees of Meso Scale Diagnostics (MSD). The rest of the authors declare that they have no conflicts of interest relevant to this manuscript., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)