The fate of protective immunity following mild severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection remains ill defined. Here, we characterize antibody responses in a cohort of participants recovered from mild SARS-CoV-2 infection with follow-up to 6 months. We measure immunoglobulin A (IgA), IgM, and IgG binding and avidity to viral antigens and assess neutralizing antibody responses over time. Furthermore, we correlate the effect of fever, gender, age, and time since symptom onset with antibody responses. We observe that total anti-S trimer, anti-receptor-binding domain (RBD), and anti-nucleocapsid protein (NP) IgG are relatively stable over 6 months of follow-up, that anti-S and anti-RBD avidity increases over time, and that fever is associated with higher levels of antibodies. However, neutralizing antibody responses rapidly decay and are strongly associated with declines in IgM levels. Thus, while total antibody against SARS-CoV-2 may persist, functional antibody, particularly IgM, is rapidly lost. These observations have implications for the duration of protective immunity following mild SARS-CoV-2 infection.

Summary The human malaria parasite Plasmodium vivax remains vastly understudied, mainly due to the lack of suitable laboratory models. Here, we report a humanized mouse model to test interventions that block P. vivax parasite transition from liver stage infection to blood stage infection. Human liver-chimeric FRGN huHep mice infected with P. vivax sporozoites were infused with human reticulocytes, allowing transition of exo-erythrocytic merozoites to reticulocyte infection and development into all erythrocytic forms, including gametocytes, in vivo. In order to test the utility of this model for preclinical assessment of interventions, the invasion blocking potential of a monoclonal antibody targeting the essential interaction of the P. vivax Duffy Binding Protein with the Duffy antigen receptor was tested by passive immunization. This antibody inhibited invasion by over 95%, providing unprecedented in vivo evidence that PvDBP constitutes a promising blood stage vaccine candidate and proving our model highly suitable to test blood stage interventions.

Highlights d We isolate a non-neutralizing antibody from PyCSPimmunized BALB/cJ mice d A non-neutralizing Ab, RAM1, abrogates the blocking capacity of an aCSP NAb d A non-neutralizing Ab, RAM1, reduces the vaccine efficacy in mice in vivo d Further exploration for the role of pre-existing nNAbs in the field is warranted

We present a microsphere-based flow cytometry assay that quantifies the ability of plasma to inhibit the binding of spike protein to angiotensin converting enzyme 2 (ACE2). Plasma from 22 subjects who recovered from mild Coronavirus disease 2019 (COVID-19) and expressed anti-spike-trimer IgGs inhibited ACE2-spike binding to a greater degree than controls. The degree of inhibition correlated with anti-spike IgG levels, neutralizing titers in a pseudotyped lentiviral assay, and the presence of fever during illness. This inhibition assay may be broadly useful to quantify the functional antibody response of recovered COVID-19 patients or vaccine recipients in a cell-free assay system.

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