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Abstract The changing landscape of SARS-CoV-2 Spike protein is linked to the emergence of variants, immune-escape and reduced efficacy of the existing repertoire of anti-viral antibodies. The functional activity of neutralizing antibodies is linked to their quaternary changes occurring as a result of antibody-Spike trimer interactions. Here, we reveal the conformational dynamics and allosteric perturbations linked to binding of novel human antibodies and the viral Spike protein. We identified epitope hotspots, and associated changes in Spike dynamics that distinguish weak, moderate and strong neutralizing antibodies. We show the impact of mutations in Wuhan-Hu-1, Delta, and Omicron variants on differences in the antibody-induced conformational changes in Spike and illustrate how these render certain antibodies ineffective. Antibodies with similar binding affinities may induce destabilizing or stabilizing allosteric effects on Spike, with implications for neutralization efficacy. Our results provide mechanistic insights into the functional modes and synergistic behavior of human antibodies against COVID-19 and may assist in designing effective antiviral strategies.

Abstract Hepatitis B Virus (HBV) is a hepadnavirus that is the principal pathogen underlying viral liver disease in human populations. In this study, we describe the isolation and characterization of a fully human monoclonal antibody for HBV. This HuMab was isolated by a combinatorial screen of the memory B-cell repertoire from an acute/recovered HBV-infected patient. Lead candidate selection was based upon strong binding and neutralizing activity for live HBV. We provide a detailed biochemical/biophysical, and subclass characterization of its specificity and affinity against all of the principal HBV genotypes combined with a functional analysis of its in vitro activity. We also demonstrate its potential as a prophylaxis/therapy in vivo using human liver chimeric mouse models for HBV infection. These data have important implications for our understanding of natural human immunity to HBV and suggest that this potentially represents a new antibody-based anti-viral candidate for prophylaxis and/or therapy for HBV infection.

Kongsuphol et al. develop a paper-based, vertical flow assay to detect SARS-CoV-2 neutralizing antibodies. The point-of-care assay has comparable performance to lab-based tests and provides results in 10 min.

Abstract Lactating women can produce protective antibodies in their milk after vaccination, which has informed antenatal vaccination programs for diseases such as influenza and pertussis. However, whether SARS-CoV-2-specific antibodies are produced in human milk as a result of COVID-19 vaccination is still unclear. In this study, we show that lactating mothers who received the BNT162b2 vaccine secreted SARS-CoV-2-specific IgA and IgG antibodies into milk, with the most significant increase at 3–7 days post-dose 2. Virus-specific IgG titers were stable out to 4–6 weeks after dose 2. In contrast, SARS-CoV-2-specific IgA levels showed substantial decay. Vaccine mRNA was detected in few milk samples (maximum of 2 ng/ml), indicative of minimal transfer. Additionally, infants who consumed post-vaccination human milk had no reported adverse effects up to 28 days post-ingestion. Our results define the safety and efficacy profiles of the vaccine in this demographic and provide initial evidence for protective immunity conferred by milk-borne SARS-CoV-2-specific antibodies. Taken together, our study supports recommendations for uninterrupted breastfeeding subsequent to mRNA vaccination against COVID-19.

Abstract There is clinical need for a quantifiable point‐of‐care (PoC) SARS‐CoV‐2 neutralizing antibody (nAb) test that is adaptable with the pandemic's changing landscape. Here, we present a rapid and semi‐quantitative nAb test that uses finger stick or venous blood to assess the nAb response of vaccinated population against wild‐type (WT), alpha, beta, gamma, and delta variant RBDs. It captures a clinically relevant range of nAb levels, and effectively differentiates prevaccination, post first dose, and post second dose vaccination samples within 10 min. The data observed against alpha, beta, gamma, and delta variants agrees with published results evaluated in established serology tests. Finally, our test revealed a substantial reduction in nAb level for beta, gamma, and delta variants between early BNT162b2 vaccination group (within 3 months) and later vaccination group (post 3 months). This test is highly suited for PoC settings and provides an insightful nAb response in a postvaccinated population.