Uses and Challenges of Antiviral Polyclonal and Monoclonal Antibody Therapies

Pharmaceutics, Год журнала: 2023, Номер 15(5), С. 1538 - 1538

Опубликована: Май 19, 2023

Viral diseases represent a major public health concerns and ever-present risks for developing into future pandemics. Antiviral antibody therapeutics, either alone or in combination with other therapies, emerged as valuable preventative treatment options, including during global emergencies. Here we will discuss polyclonal monoclonal antiviral focusing on the unique biochemical physiological properties that make them well-suited therapeutic agents. We describe methods of characterization potency assessment throughout development, highlighting similarities differences between products appropriate. In addition, consider benefits challenges antibodies when used types therapeutics. Lastly, novel approaches to development identify areas would benefit from additional research.

Язык: Английский

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Comparative analysis of SARS-CoV-2 neutralization titers reveals consistency between human and animal model serum and across assays

Science Translational Medicine, Год журнала: 2024, Номер 16(747)

Опубликована: Май 15, 2024

The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires ongoing monitoring to judge the ability newly arising variants escape immune response. A surveillance system necessitates an understanding differences in neutralization titers measured different assays and using human animal serum samples. We compared 18 datasets generated human, hamster, mouse six assays. Datasets model samples showed higher titer magnitudes than this comparison. Fold change ancestral SARS-CoV-2, immunodominance patterns, antigenic maps were similar among Most yielded consistent results, except for fold cytopathic effect Hamster a surrogate first-infection These results inform transition SARS-CoV-2 variation from dependence on utilization models.

Язык: Английский

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Tracking Immunity: An Increased Number of COVID-19 Boosters Increases the Longevity of Anti-RBD and Anti-RBD-Neutralizing Antibodies

Vaccines, Год журнала: 2025, Номер 13(1), С. 61 - 61

Опубликована: Янв. 12, 2025

Background/Objectives: Since the World Health Organization declared COVID-19 a pandemic in March 2020, virus has caused multiple waves of infection globally. Arizona State University (ASU), largest four-year university United States, offers uniquely diverse setting for assessing immunity within large community. This study aimed to test our hypothesis that an increased number exposures SARS-CoV-2 RBD through vaccination/boosters/infection will increase antibody seroprevalence by increasing longevity anti-RBD and anti-RBD-neutralizing antibodies. Methods: A serosurvey was conducted at ASU from 30 January 3 February 2023. Participants completed questionnaires about demographics, respiratory history, symptoms, vaccination status. Blood samples were analyzed anti-receptor binding domain (RBD) IgG anti-nucleocapsid (NC) antibodies, offering comprehensive view both natural vaccination. Results: The antibodies 96.2% (95% CI: 94.8–97.2%), 64.9% 61.9–67.8%) participants had anti-NC Anti-RBD levels correlated strongly with neutralizing levels, who received more vaccine doses showed higher Increasing and/or resulted long-lasting Conclusions: high observed reflect substantial uptake this population. Ongoing efforts, especially as new variants emerge, are essential maintaining protective levels. These findings underscore importance sustained public health initiatives support broad-based protection.

Язык: Английский

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SARS-CoV-2 Fusion Peptide-Directed Antibodies Elicited by Natural Infection Mediate Broad Sarbecovirus Neutralization

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Март 5, 2025

SUMMARY Studies have demonstrated that repeated mRNA vaccination enhances the breadth of neutralization against diverse SARS-CoV-2 variants. However, development antibodies capable neutralizing across Coronavirinae subfamily is poorly understood. In this study, we analyze serum samples to determine their and potency identify antigenic targets. Using a cohort older individuals healthcare workers, track correlates broad responses, including fusion peptide (FP) antibody elicitation. We find although broadly responses are often result RBD-specific antibodies, rare subset donors produce FP-specific responses. Interestingly, not observed in COVID-naive irrespective regimen, but rather, they occur following natural infection or vaccine breakthrough. This study highlights epitope targets underpinning coronaviruses suggests existing vaccines insufficient promote elicitation FP-directed coronavirus antibodies.

Язык: Английский

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Functional and antigenic landscape of the Nipah virus receptor binding protein

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Апрель 19, 2024

Nipah virus recurrently spills over to humans, causing fatal infections. The viral receptor-binding protein (RBP or G) attaches host receptors and is a major target of neutralizing antibodies. Here we use deep mutational scanning measure how all amino-acid mutations the RBP affect cell entry, receptor binding, escape from We identify functionally constrained regions RBP, including sites involved in oligomerization, along with that differentially modulate binding its two ephrin receptors. map for six anti-RBP antibodies, find few antigenic are present natural strains. Our findings offer insights into potential functional evolution can inform development antibody therapies vaccines.

Язык: Английский

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Comparative Analysis of SARS-CoV-2 Antigenicity across Assays and in Human and Animal Model Sera

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Сен. 27, 2023

Abstract The antigenic evolution of SARS-CoV-2 requires ongoing monitoring to judge the immune escape newly arising variants. A surveillance system necessitates an understanding differences in neutralization titers measured different assays and using human animal sera. We compared 18 datasets generated human, hamster, mouse sera, six assays. Titer magnitude was lowest intermediate highest Fold change, immunodominance patterns maps were similar among Most yielded results, except for fold change cytopathic effect Not enough data available conclusively judging but hamster sera a consistent surrogate first-infection

Язык: Английский

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Identification of broad, potent antibodies to functionally constrained regions of SARS-CoV-2 spike following a breakthrough infection

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2022, Номер unknown

Опубликована: Дек. 16, 2022

The antiviral benefit of antibodies can be compromised by viral escape especially for rapidly evolving viruses. Therefore, durable, effective must both broad and potent to counter newly emerging, diverse strains. Discovery such is critically important SARS-CoV-2 as the global emergence new variants concern (VOC) has efficacy therapeutic vaccines. We describe a collection neutralizing monoclonal (mAbs) isolated from an individual who experienced breakthrough infection with Delta VOC. Four mAbs potently neutralize Wuhan-Hu-1 vaccine strain, VOC, also retain potency against Omicron VOCs through BA.4/BA.5 in pseudovirus-based authentic virus assays. Three recently circulating XBB.1.5 BQ.1.1 one neutralizes SARS-CoV-1. these was greater than all but that had been approved applications. target distinct epitopes on spike glycoprotein, three receptor binding domain (RBD) invariant region downstream RBD subdomain 1 (SD1). pathways we defined at single amino acid resolution deep mutational scanning show they conserved, functionally constrained regions suggesting could incur fitness cost. Overall, are novel their breadth across VOCs, epitope specificity, include highly mAb targeting rare outside SD1.

Язык: Английский

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

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Фев. 28, 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 describe collection mAbs two convalescent individuals target multiple subdomain can be grouped into at least five epitope classes. Most did not neutralize with exception C20.119, which bound highly conserved fusion peptide showed broad neutralization activity across SARS-CoV-2, SARS-CoV-1, closely related zoonotic sarbecoviruses. Several tested mediated antibody-dependent cellular cytotoxicity (ADCC) levels similar mAb S309 was previously authorized treatment infections. Three ADCC function also trimers HCoVs, MERS-CoV HCoV-HKU1. Our findings suggest are diverse epitopes S2, including functional HCoV sarbecovirus breadth likely functionally spike. These could developed potential future pandemics, while providing insight ideal eliciting response.

Язык: Английский

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Bispecific antibodies with broad neutralization potency against SARS-CoV-2 variants of concern

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Май 6, 2024

Abstract The ongoing emergence of SARS-CoV-2 variants concern (VOCs) that reduce the effectiveness antibody therapeutics necessitates development next-generation modalities are resilient to viral evolution. Here, we characterized N-terminal domain (NTD) and receptor binding (RBD)-specific monoclonal antibodies previously isolated from COVID-19 convalescent donors for their activity against emergent VOCs. Among these, NTD-specific C1596 displayed greatest breadth VOCs, with cryo-EM structural analysis revealing recognition a distinct NTD epitope outside site i antigenic supersite. Given C1596’s favorable profile, designed series bispecific (bsAbs) termed CoV2-biRNs, featured both RBD specificities. Notably, two C1596-inclusive bsAbs, CoV2-biRN5 CoV2-biRN7, retained potent in vitro neutralization all Omicron tested, including XBB.1.5, EG.5.1, BA.2.86, contrasting diminished potency parental delivered as monotherapies or cocktail. Furthermore, prophylactic delivery significantly reduced load within lungs K18-hACE2 mice following challenge XBB.1.5. In conclusion, our NTD-RBD bsAbs offer promising potential design resilient, One Sentence Summary Bispecific highly cross-reactive demonstrate resilience concern.

Язык: Английский

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Engineering a SARS-CoV-2 vaccine targeting the RBD cryptic-face via immunofocusing

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июнь 5, 2024

The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein is main target neutralizing antibodies. Although they are infrequently elicited during infection or vaccination, antibodies that bind to conformation-specific cryptic face RBD display remarkable breadth binding and neutralization across

Язык: Английский

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