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

Pardi and colleagues report on a vaccine platform in which purified, antigen-encoding, nucleoside-modified mRNA is encapsulated in lipid nanoparticles. Immunization with this vaccine elicits potent T follicular helper cell, germinal center B cell, and protective, neutralizing antibody responses.

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 HIV-1 broadly neutralizing antibodies (bnAbs) develop in a subset of infected adults and exhibit high levels of somatic hypermutation (SHM) due to years of affinity maturation. There is no precedent for eliciting highly mutated antibodies by vaccination, nor is it practical to wait years for a desired response. Infants develop broad responses early, which may suggest a more direct path to generating bnAbs. Here, we isolated ten neutralizing antibodies (nAbs) contributing to plasma breadth of an infant at ~1 year post-infection, including one with cross-clade breadth. The nAbs bind to envelope trimer from the transmitted virus suggesting this interaction may have initiated development of the infant nAbs. The infant cross-clade bnAb targets the N332 supersite on envelope, but unlike adult bnAbs targeting this site, lacks indels and has low SHM. The identification of this infant bnAb illustrates that HIV-1-specific neutralization breadth can develop without prolonged affinity maturation and extensive SHM.

Malnutrition substantially increases susceptibility to Entamoeba histolytica in children. Leptin is a hormone produced by adipocytes that inhibits food intake, influences the immune system, and is suppressed in malnourished children. Therefore we hypothesized that diminished leptin function may increase susceptibility to E. histolytica infection. We prospectively observed a cohort of children, beginning at preschool age, for infection by the parasite E. histolytica every other day over 9 years and evaluated them for genetic variants in leptin (LEP) and the leptin receptor (LEPR). We found increased susceptibility to intestinal infection by this parasite associated with an amino acid substitution in the cytokine receptor homology domain 1 of LEPR. Children carrying the allele for arginine (223R) were nearly 4 times more likely to have an infection compared with those homozygous for the ancestral glutamine allele (223Q). An association of this allele with amebic liver abscess was also determined in an independent cohort of adult patients. In addition, mice carrying at least 1 copy of the R allele of Lepr were more susceptible to infection and exhibited greater levels of mucosal destruction and intestinal epithelial apoptosis after amebic infection. These findings suggest that leptin signaling is important in mucosal defense against amebiasis and that polymorphisms in the leptin receptor explain differences in susceptibility of children in the Bangladesh cohort to amebiasis.