Biology subjects

Lavinder, J.

Publications and source records attributed to Lavinder, J..

3 recordsLinked to original sources

bioRxiv2025

The N-terminal region of malaria vaccine candidate Plasmodium falciparum asparagine-rich merozoite antigen is immunodominant and targeted by polyreactive antibodies

The development of malaria blood-stage vaccines has been hampered by sequence variation in many Plasmodium falciparum proteins involved in erythrocyte invasion. In the past few years, asparagine-rich merozoite antigen (PfARMA) has emerged as a potential vaccine candidate due to its low amino acid sequence diversity and the association between anti-PfARMA antibody levels and protection to malaria. Here, we used samples from P. falciparum-exposed individuals to study naturally acquired B cell and antibody responses to PfARMA. B cell responses to PfARMA were dominated by IgM+ B cells that recognized the N-terminal intrinsically disordered region 1 (IDR1) of PfARMA. A human monoclonal antibody (hmAb) to IDR1 was non-neutralizing, while a second hmAb binding to the folded domain showed weak neutralizing activity. Both PfARMA-specific plasma IgM and IgG responses predominately targeted IDR1 and their levels increased with P. falciparum exposure. However, in contrast to previous reports, these antibody responses did not correlate with protection in age and exposure-matched children. Interestingly, approximately 30% of unexposed individuals had IgG that also targeted IDR1 and was polyreactive, binding to regions with high asparagine content. Finally, we determined that PfARMA is located in or near PfEBA-175+ micronemes. These data suggest that while IgG to the folded domain of PfARMA may inhibit parasite growth, antibody responses to PfARMA are primarily directed to IDR1 and may not directly contribute to protection against malaria.

immunology↗

bioRxiv2021

Synthetic repertoires derived from convalescent COVID-19 patients enable discovery of SARS-CoV-2 neutralizing antibodies and a novel quaternary binding modality

The ongoing evolution of SARS-CoV-2 into more easily transmissible and infectious variants has sparked concern over the continued effectiveness of existing therapeutic antibodies and vaccines. Hence, together with increased genomic surveillance, methods to rapidly develop and assess effective interventions are critically needed. Here we report the discovery of SARS-CoV-2 neutralizing antibodies isolated from COVID-19 patients using a high-throughput platform. Antibodies were identified from unpaired donor B-cell and serum repertoires using yeast surface display, proteomics, and public light chain screening. Cryo-EM and functional characterization of the antibodies identified N3-1, an antibody that binds avidly (Kd,app = 68 pM) to the receptor binding domain (RBD) of the spike protein and robustly neutralizes the virus in vitro. This antibody likely binds all three RBDs of the trimeric spike protein with a single IgG. Importantly, N3-1 equivalently binds spike proteins from emerging SARS-CoV-2 variants of concern, neutralizes UK variant B.1.1.7, and binds SARS-CoV spike with nanomolar affinity. Taken together, the strategies described herein will prove broadly applicable in interrogating adaptive immunity and developing rapid response biological countermeasures to emerging pathogens.

synthetic biology↗

bioRxiv2020

Relationship between Anti-Spike Protein Antibody Titers and SARS-CoV-2 In Vitro Virus Neutralization in Convalescent Plasma

Newly emerged pathogens such as SARS-CoV-2 highlight the urgent need for assays that detect levels of neutralizing antibodies that may be protective. We studied the relationship between anti-spike ectodomain (ECD) and anti-receptor binding domain (RBD) IgG titers, and SARS-CoV-2 virus neutralization (VN) titers generated by two different in vitro assays using convalescent plasma samples obtained from 68 COVID-19 patients, including 13 who donated plasma multiple times. Only 23% (16/68) of donors had been hospitalized. We also studied 16 samples from subjects found to have anti-spike protein IgG during surveillance screening of asymptomatic individuals. We report a strong positive correlation between both plasma anti-RBD and anti-ECD IgG titers, and in vitro VN titer. Anti-RBD plasma IgG correlated slightly better than anti-ECD IgG titer with VN titer. The probability of a VN titer [≥]160 was 80% or greater with anti-RBD or anti-ECD titers of [≥]1:1350. Thirty-seven percent (25/68) of convalescent plasma donors lacked VN titers [≥]160, the FDA-recommended level for convalescent plasma used for COVID-19 treatment. Dyspnea, hospitalization, and disease severity were significantly associated with higher VN titer. Frequent donation of convalescent plasma did not significantly decrease either VN or IgG titers. Analysis of 2,814 asymptomatic adults found 27 individuals with anti-RBD or anti-ECD IgG titers of [≥]1:1350, and evidence of VN [≥]1:160. Taken together, we conclude that anti-RBD or anti-ECD IgG titers can serve as a surrogate for VN titers to identify suitable plasma donors. Plasma anti-RBD or anti-ECD titer of [≥]1:1350 may provide critical information about protection against COVID-19 disease.

immunology↗