HIGHLIGHTSd Cross-sectional study of 44 hospitalized COVID-19 patients d RBD-specific IgG responses detectable in all patients 6 days after PCR confirmation d Neutralizing titers are detectable in all patients 6 days after PCR confirmation d RBD-specific IgG titers correlate with the neutralizing potency

28SARS-CoV-2 is currently causing a devastating pandemic and there is a pressing need to 29 understand the dynamics, specificity, and neutralizing potency of the humoral immune response 30 during acute infection. Herein, we report the dynamics of antibody responses to the receptor-31 binding domain (RBD) of the spike protein and virus neutralization activity in 44 COVID-19 32 patients. RBD-specific IgG responses were detectable in all patients 6 days after PCR 33 confirmation. Using a clinical isolate of SARS-CoV-2, neutralizing antibody titers were also 34 detectable in all patients 6 days after PCR confirmation. The magnitude of RBD-specific IgG 35 binding titers correlated strongly with viral neutralization. In a clinical setting, the initial analysis of 36 the dynamics of RBD-specific IgG titers was corroborated in a larger cohort of PCR-confirmed 37 patients (n=231). These findings have important implications for our understanding of protective 38 immunity against SARS-CoV-2, the use of immune plasma as a therapy, and the development of 39 much-needed vaccines. 40 41

Summary Zika virus (ZIKV), which emerged in regions endemic to Dengue virus (DENV), is vertically transmitted and results in adverse pregnancy outcomes. Antibodies to DENV can cross-react with ZIKV, but whether these antibodies influence ZIKV vertical transmission remains unclear. Here, we find that DENV antibodies increase ZIKV infection of placental macrophages (Hofbauer cells [HCs]) from 10% to over 80% and enhance infection of human placental explants. ZIKV-anti-DENV antibody complexes increase viral binding and entry into HCs but also result in blunted type I IFN, proinflammatory cytokine and antiviral responses. Additionally, ZIKV infection of HCs and human placental explants are enhanced in an IgG subclass-dependent manner, and targeting FcRn reduces ZIKV replication in human placental explants. Collectively, these findings support a role for pre-existing DENV antibodies in enhancement of ZIKV infection of select placental cell types and indicate that pre-existing immunity to DENV should be considered when addressing in ZIKV vertical transmission.

We characterized the acute B cell response in adults with cholera by analyzing the repertoire, specificity, and functional characteristics of 138 monoclonal antibodies (MAbs) generated from single-cell-sorted plasmablasts. We found that the cholera-induced responses were characterized by high levels of somatic hypermutation and large clonal expansions. A majority of the expansions targeted cholera toxin (CT) or lipopolysaccharide (LPS). Using a novel proteomics approach, we were able to identify sialidase as another major antigen targeted by the antibody response to Vibrio cholerae infection. Antitoxin MAbs targeted both the A and B subunits, and most were also potent neutralizers of enterotoxigenic Escherichia coli heat-labile toxin. LPS-specific MAbs uniformly targeted the O-specific polysaccharide, with no detectable responses to either the core or the lipid moiety of LPS. Interestingly, the LPS-specific antibodies varied widely in serotype specificity and functional characteristics. One participant infected with the Ogawa serotype produced highly mutated LPS-specific antibodies that preferentially bound the previously circulating Inaba serotype. This demonstrates durable memory against a polysaccharide antigen presented at the mucosal surface and provides a mechanism for the long-term, partial heterotypic immunity seen following cholera.