Protective non-neutralizing SARS-CoV-2 monoclonal antibodies

Trends in Immunology, Journal Year: 2024, Volume and Issue: 45(8), P. 609 - 624

Published: July 20, 2024

Recent studies show an important role for non-neutralizing anti-spike antibodies, including monoclonal antibodies (mAbs), in robustly protecting against SARS-CoV-2 infection. These mAbs use Fc-mediated functions such as complement activation, phagocytosis, and cellular cytotoxicity. There is untapped potential using durable antibody treatments; because of their available conserved epitopes, they may not be sensitive to virus mutations neutralizing mAbs. Here, we discuss evidence mAb-mediated protection We explore how mAb can enhanced via novel antibody-engineering techniques. Important questions remain answered regarding the characteristics protective mAbs, models assays used study, risks ensuing detrimental inflammation, well durability mechanisms protection.

Language: Английский

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The S2 subunit of spike encodes diverse targets for functional antibody responses to SARS-CoV-2

PLoS Pathogens, Journal Year: 2024, Volume and Issue: 20(8), P. e1012383 - e1012383

Published: Aug. 2, 2024

The SARS-CoV-2 virus responsible for the COVID-19 global pandemic has exhibited a striking capacity viral evolution that drives continued evasion from vaccine and infection-induced immune responses. Mutations in receptor binding domain of S1 subunit spike glycoprotein have led to considerable escape antibody responses, reducing efficacy vaccines monoclonal (mAb) therapies. Therefore, there is need interrogate more constrained regions spike, such as S2 subdomain. Here, we present collection mAbs two convalescent individuals target multiple S2, including outside those commonly reported. One mAbs, C20.119, which bound highly conserved epitope fusion peptide, was able broadly neutralize across variants, SARS-CoV-1, closely related zoonotic sarbecoviruses. majority were non-neutralizing; however, many them could mediate antibody-dependent cellular cytotoxicity (ADCC) at levels similar S1-targeting mAb S309 previously authorized treatment infections. Several with ADCC function also trimers other human coronaviruses (HCoVs), MERS-CoV HCoV-HKU1. Our findings suggest can diverse epitopes functional HCoV sarbecovirus breadth likely functionally spike. These be developed potential future pandemics, while providing insight into ideal eliciting broad response.

Language: Английский

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In vivo determination of protective antibody thresholds for SARS-CoV-2 variants using mouse models

Emerging Microbes & Infections, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 24, 2025

Neutralizing antibody titers have been shown to correlate with immune protection against COVID-19 and can be used estimate vaccine effectiveness. Numerous studies explored the relationship between neutralizing antibodies protection. However, there remains a lack of quantitative data directly assessing minimum effective protective titer in vivo. In this study, we utilized eight cohorts participants diverse backgrounds for evaluation response. To precisely assess lower threshold required SARS-CoV-2 infections, employed plasma adoptive transfer from different into mice. This study demonstrated that recipient mice correlated well those human donors, positive linear correlation was observed mouse recipients transferred titer. A pseudotyped virus greater than 7 identified as necessary reduce viral infected mice, establishing crucial baseline Furthermore, despite variability backgrounds, these cohorts' exhibited similar finding has significant implications design assessment competence.

Language: Английский

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A Versatile High‐Throughput Single‐Cell Screening Platform for Profiling Antigen‐Specific Long‐Lived B Cells in Blood and Bone Marrow

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: April 9, 2025

Abstract Antigen‐specific B cells play a crucial role in the long‐term immune response following infection or vaccination, differentiating into antibody‐secreting (ASCs) and memory (MBCs). However, profiling ASCs is challenging primarily due to their lack of membrane‐bound surface cell receptors. In this study, Modular Superhydrophobic Microwell Array Chip (MoSMAR‐chip) introduced as versatile, cost‐effective, high‐throughput platform for identifying characterizing individual antigen‐specific MBCs at single‐cell level within seven days. Using platform, comprehensive analyses single could be performed from bone marrows coronavirus disease 2019 (COVID‐19) vaccine‐immunized mice diverse set antibodies capable neutralizing highly divergent JN1 variant severe acute respiratory syndrome 2 (SARS‐CoV‐2) were identified. These results demonstrate that MoSMAR‐chip facilitates efficient multi‐omics functional ASCs, offering powerful tool investigating complex immunity clinical conditions, such infectious diseases, autoimmunity, beyond.

Language: Английский

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Vaccine Strategies Against RNA Viruses: Current Advances and Future Directions

Vaccines, Journal Year: 2024, Volume and Issue: 12(12), P. 1345 - 1345

Published: Nov. 28, 2024

The development of vaccines against RNA viruses has undergone a rapid evolution in recent years, particularly driven by the COVID-19 pandemic. This review examines key roles that viruses, with their high mutation rates and zoonotic potential, play fostering vaccine innovation. We also discuss both traditional modern platforms impact new technologies, such as artificial intelligence, on optimizing immunization strategies. evaluates various platforms, ranging from approaches (inactivated live-attenuated vaccines) to technologies (subunit vaccines, viral bacterial vectors, nucleic acid mRNA DNA, phage-like particle vaccines). To illustrate these platforms’ practical applications, we present case studies developed for SARS-CoV-2, influenza, Zika, dengue. Additionally, assess role intelligence predicting mutations enhancing design. underscore successful application RNA-based fight COVID-19, which saved millions lives. Current clinical trials dengue continue show promise, highlighting growing efficacy adaptability platforms. Furthermore, is driving improvements candidate optimization providing predictive models evolution, our ability respond future outbreaks. Advances technology, success highlight potential combating viruses. Ongoing demonstrate platform adaptability, while enhances design mutations. Integrating innovations One Health approach, unites human, animal, environmental health, essential strengthening global preparedness virus threats.

Language: Английский

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Epitope mapping via in vitro deep mutational scanning methods and its applications

Journal of Biological Chemistry, Journal Year: 2024, Volume and Issue: unknown, P. 108072 - 108072

Published: Dec. 1, 2024

Language: Английский

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Structural Immunology of SARS‐CoV‐2

Immunological Reviews, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 27, 2024

The SARS-CoV-2 spike (S) protein has undergone significant evolution, enhancing both receptor binding and immune evasion. In this review, we summarize ongoing efforts to develop antibodies targeting various epitopes of the S protein, focusing on their neutralization potency, breadth, escape mechanisms. Antibodies receptor-binding site (RBS) typically exhibit high neutralizing potency but are frequently evaded by mutations in variants. contrast, conserved regions, such as S2 stem helix fusion peptide, broader reactivity generally lower potency. However, several broadly have demonstrated exceptional efficacy against emerging variants, including latest omicron subvariants, underscoring potential vulnerable sites RBS-A RBS-D/CR3022. We also highlight public classes different protein. targeted present opportunities for germline-targeting vaccine strategies. Overall, developing escape-resistant, potent effective vaccines remains crucial combating future This review emphasizes importance identifying key utilizing antibody affinity maturation inform therapeutic design.

Language: Английский

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Dissecting human monoclonal antibody responses from mRNA- and protein-based XBB.1.5 COVID-19 monovalent vaccines

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 16, 2024

The emergence of highly contagious and immune-evasive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has required reformulation disease 2019 (COVID-19) vaccines to target those new specifically. While previous infections booster vaccinations can enhance variant neutralization, it is unclear whether the monovalent version, administered using either mRNA or protein-based vaccine platforms, elicit

Language: Английский

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Antigen Delivery Platforms for Next-Generation Coronavirus Vaccines

Vaccines, Journal Year: 2024, Volume and Issue: 13(1), P. 30 - 30

Published: Dec. 31, 2024

The COVID-19 pandemic, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is in its sixth year and being maintained inability of current spike-alone-based vaccines to prevent transmission leading continuous emergence variants sub-variants concern (VOCs). This underscores critical need for next-generation broad-spectrum pan-Coronavirus (pan-CoV vaccine) break this cycle end pandemic. development a pan-CoV vaccine offering protection against wide array VOCs requires two key elements: (1) identifying protective antigens that are highly conserved between passed, current, future VOCs; (2) developing safe efficient antigen delivery system induction broad-based long-lasting B- T-cell immunity. review will present state platforms involving multifaceted approach, including bioinformatics, molecular structural biology, immunology, advanced computational methods; discuss challenges facing effective platforms; (3) highlight potential nucleoside-modified mRNA encapsulated lipid nanoparticles (LNP) as platform well suited needs vaccine, such ability induce immunity amenable large-scale manufacturing safely provide durable threats.

Language: Английский

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