Endogenous antibody responses in REGN-COV2-treated SARS-CoV-2-infected individuals DOI Creative Commons
Ashwini Kurshan, Luke B. Snell,

Lucie Prior

et al.

Oxford Open Immunology, Journal Year: 2023, Volume and Issue: 4(1)

Published: Jan. 1, 2023

Neutralizing monoclonal antibodies (mAbs) targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike glycoprotein have been developed for the treatment of COVID-19. Whilst antibody therapy has shown to reduce risk COVID-19-associated hospitalization and death, there is limited understanding endogenous immunity SARS-CoV-2 generated in mAb-treated patients therefore ongoing susceptibility future infections. Here we measure response SARS-CoV-2-infected individuals treated with REGN-COV2 (Ronapreve). We show that majority unvaccinated, delta-infected REGN-COV2-treated individuals, an generated, but, like untreated, was a neutralization breadth. However, some vaccinated who were seronegative at infection baseline unvaccinated failed produce immune following demonstrating importance mAb patient populations.

Language: Английский

RBD-depleted SARS-CoV-2 spike generates protective immunity in cynomolgus macaques DOI Creative Commons
Hélène Letscher,

Delphine Guilligay,

Grégory Effantin

et al.

npj Vaccines, Journal Year: 2025, Volume and Issue: 10(1)

Published: March 30, 2025

Abstract The SARS-CoV-2 pandemic revealed the rapid evolution of circulating strains. This led to new variants carrying mostly mutations within receptor binding domain, which is immunodominant upon immunization and infection. In order steer immune response away from RBD epitopes more conserved domains, we generated S glycoprotein trimers without stabilized them by formaldehyde cross-linking. cryoEM structure demonstrated that SΔRBD folds into native prefusion conformation, one specific cross-link between S2 protomers. was coated onto lipid vesicles, produce synthetic virus-like particles, SΔRBD-LV, were utilized in a heterologous prime-boost strategy. Immunization cynomolgus macaques either three times with mRNA Comirnaty vaccine or two followed SΔRBD-LV showed boost induced similar antibody titers neutralization different variants, including omicron. Upon challenge omicron XBB.3, both only Comirnaty/SΔRBD-LV vaccination schemes conferred overall protection infection for schemes. However, indicated better against lung than strategy alone. Together our findings indicate highly immunogenic provides improved compared third indicative superior antibody-based protection.

Language: Английский

Citations

0
A systematic evaluation of the language-of-viral-escape model using multiple machine learning frameworks DOI Creative Commons

Brent Allman,

Luiz Angêlo Vieira, Daniel J. Diaz

et al.

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

Published: Sept. 8, 2024

Abstract Predicting the evolutionary patterns of emerging and endemic viruses is key for mitigating their spread in host populations. In particular, it critical to rapidly identify mutations with potential immune escape or increased disease burden (variants concern). Knowing which circulating are such variants concern can inform treatment mitigation strategies as alternative vaccines targeted social distancing. A recent study proposed that be identified using two quantities extracted from protein language models, grammaticality semantic change. These defined analogy concepts natural processing. Grammaticality intended a measure whether variant viral viable, change escape. Here, we systematically test this hypothesis, taking advantage several high-throughput datasets have become available, also testing additional machine learning models calculating metric. We find viability, though more traditional metric ΔΔ G appears effective. By contrast, do not compelling evidence useful tool identifying mutations.

Language: Английский

Citations

2
Escalating combinations of enhanced infectivity and immune escape define SARS-CoV-2 Omicron lineage replacement DOI Creative Commons
Nicholas F. G. Chen, Kien Pham, Chrispin Chaguza

et al.

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

Published: Jan. 4, 2024

Abstract In 2022, consecutive sweeps of the highly transmissible SARS-CoV-2 Omicron-family maintained high viral transmission levels despite extensive antigen exposure on population level resulting from both vaccinations and infections. To better understand variant fitness in context dynamic immunity landscape we aimed to dissect interplay between advantages emerging Omicron lineages population-level. We evaluated relative contribution higher intrinsic transmissibility or immune escape by analyzing data collected through our local genomic surveillance program Connecticut, USA. compared growth rates, estimated infections, effective reproductive average copy numbers, likelihood for causing vaccine break-through Using these population-level data, find that newly reach dominance a specific combination enhanced varies over time depending state host-population. similar frameworks integrate whole genome sequencing together with clinical, laboratory, epidemiological can advance knowledge host-pathogen dynamics post-emergence phase be applied other communicable diseases beyond SARS-CoV-2.

Language: Английский

Citations

0
Endogenous antibody responses in REGN-COV2-treated SARS-CoV-2-infected individuals DOI Creative Commons
Ashwini Kurshan, Luke B. Snell,

Lucie Prior

et al.

Oxford Open Immunology, Journal Year: 2023, Volume and Issue: 4(1)

Published: Jan. 1, 2023

Neutralizing monoclonal antibodies (mAbs) targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike glycoprotein have been developed for the treatment of COVID-19. Whilst antibody therapy has shown to reduce risk COVID-19-associated hospitalization and death, there is limited understanding endogenous immunity SARS-CoV-2 generated in mAb-treated patients therefore ongoing susceptibility future infections. Here we measure response SARS-CoV-2-infected individuals treated with REGN-COV2 (Ronapreve). We show that majority unvaccinated, delta-infected REGN-COV2-treated individuals, an generated, but, like untreated, was a neutralization breadth. However, some vaccinated who were seronegative at infection baseline unvaccinated failed produce immune following demonstrating importance mAb patient populations.

Language: Английский

Citations

1