Biology subjects

Scobey, T.

Publications and source records attributed to Scobey, T..

3 recordsLinked to original sources

bioRxiv2025

A neutralizing human antibody induces movement of the HCoV-229E receptor binding domain

HCoV-229E is an endemic Alphacoronavirus that typically causes common cold-like disease in most healthy adults, but can also cause severe respiratory disease in the very young and the elderly. Although the virus was discovered over sixty years ago and undergoes continuous antigenic drift, remarkably little is known about the humoral immune response to HCoV-229E infection. Here we report the isolation of two receptor binding domain-targeting neutralizing human antibodies raised in response to natural HCoV-229E infection. One of these, DH1533, potently neutralizes HCoV-229E, binds to spike with sub-nanomolar affinity and prevents the association between the RBD and the host cell receptor aminopeptidase N. Structural characterization of this antibody bound to HCoV-229E spike delineated a neutralization-sensitive epitope on the RBD and revealed that DH1533 induces conformational flexibility in neighboring RBDs, reminiscent of the "up-and-down" kinetics observed in the related Betacoronavirus spikes. These findings provide insight into the humoral immune response to HCoV-229E infection and will serve as a guide for the design of future therapeutic interventions.

immunology↗

bioRxiv2024

Hybrid immunity to SARS-CoV-2 arises from serological recall of IgG antibodies distinctly imprinted by infection or vaccination

We used plasma IgG proteomics to study the molecular composition and temporal durability of polyclonal IgG antibodies triggered by ancestral SARS-CoV-2 infection, vaccination, or their combination ("hybrid immunity"). Infection, whether primary or post-vaccination, mainly triggered an anti-spike antibody response to the S2 domain, while vaccination predominantly induced anti-RBD antibodies. Immunological imprinting persisted after a secondary (hybrid) exposure, with >60% of the ensuing serological response originating from the initial antibodies generated during the first exposure. We highlight one instance where hybrid immunity arising from breakthrough infection resulted in a marked increase in the breadth and affinity of a highly abundant vaccination-elicited plasma IgG antibody, SC27. With an intrinsic binding affinity surpassing a theoretical maximum (KD < 5 pM), SC27 demonstrated potent neutralization of various SARS-CoV-2 variants and SARS-like zoonotic viruses (IC50 [~]0.1-1.75 nM) and provided robust protection in vivo. Cryo-EM structural analysis unveiled that SC27 binds to the RBD class 1/4 epitope, with both VH and VL significantly contributing to the binding interface. These findings suggest that exceptionally broad and potent antibodies can be prevalent in plasma and can largely dictate the nature of serological neutralization. HIGHLIGHTS{blacksquare} Infection and vaccination elicit unique IgG antibody profiles at the molecular level {blacksquare}Immunological imprinting varies between infection (S2/NTD) and vaccination (RBD) {blacksquare}Hybrid immunity maintains the imprint of first infection or first vaccination {blacksquare}Hybrid immune IgG plasma mAbs have superior neutralization potency and breadth

immunology↗

bioRxiv2021

SARS-CoV-2 Vaccines Elicit Durable Immune Responses in Infant Rhesus Macaques

Early life SARS-CoV-2 vaccination has the potential to provide lifelong protection and achieve herd immunity. To evaluate SARS-CoV-2 infant vaccination, we immunized two groups of 8 infant rhesus macaques (RMs) at weeks 0 and 4 with stabilized prefusion SARS-CoV-2 S-2P spike (S) protein, either encoded by mRNA encapsulated in lipid nanoparticles (mRNA-LNP) or mixed with 3M-052-SE, a TLR7/8 agonist in a squalene emulsion (Protein+3M-052-SE). Neither vaccine induced adverse effects. High magnitude S-binding IgG and neutralizing infectious dose 50 (ID50) >103 were elicited by both vaccines. S-specific T cell responses were dominated by IL-17, IFN-{gamma}, or TNF-. Antibody and cellular responses were stable through week 22. The S-2P mRNA-LNP and Protein-3M-052-SE vaccines are promising pediatric SARS-CoV-2 vaccine candidates to achieve durable protective immunity. One-Sentence SummarySARS-CoV-2 vaccines are well-tolerated and highly immunogenic in infant rhesus macaques

immunology↗