The Lancet Microbe, Journal Year: 2024, Volume and Issue: unknown, P. 100974 - 100974
Published: Oct. 1, 2024
Language: Английский
Cell, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 1, 2025
Nanoparticle vaccines displaying combinations of SARS-like betacoronavirus (sarbecovirus) receptor-binding domains (RBDs) could protect against SARS-CoV-2 variants and spillover zoonotic sarbecoviruses into humans. Using a computational approach, we designed RBDs selected 7 natural sarbecovirus RBDs, each predicted to fold properly abrogate antibody responses variable epitopes. were attached 60-mer nanoparticles make immunogens two (mosaic-2COMs), five (mosaic-5COM), or seven (mosaic-7COM) different for comparisons with mosaic-8b, which elicited cross-reactive antibodies protected animals from challenges. Naive COVID-19 pre-vaccinated mice immunized mosaic-7COM targeting conserved RBD epitopes, their sera exhibited higher binding neutralization titers than mosaic-8b. Mosaic-2COMs mosaic-5COM potencies some mosaic-7COM. However, more potent highly mutated Omicrons, supporting its use sarbecoviruses.
Language: Английский
Citations
3
Journal of Virology, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 16, 2025
ABSTRACT The common cold coronaviruses are a source of ongoing morbidity and mortality particularly among elderly immunocompromised individuals. While cross-reactive immune responses against multiple have been described following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection vaccination, it remains unclear if these confer any degree cross-protection the coronaviruses. A recombinant fowl adenovirus vaccine expressing SARS-CoV-2 spike protein (FAdV-9-S19) was generated, protection from challenge shown in K18-hACE2 mice. Vaccinated mice were also challenged with human (HCoV)-OC43 HCoV-NL63 by intranasal route, viral shedding lung burden reduced groups compared to unvaccinated animals. Histopathological analysis tissues revealed significantly less inflammation lower pathology scores that received FAdV-9-S19 . Because no mouse model for HCoV-229E exists, we vaccinated cynomolgus macaques evaluate HCoV-229E. Animals monitored clinical signs disease shedding. Infectious virus detected both throughout course infection; however, animals showed at time points after infection. indicated more moderate Therefore, vaccination provided model. Our study demonstrates can provide low-level beta- alphacoronaviruses. These findings important design future pan-coronavirus vaccines. IMPORTANCE individuals, is currently available. Cross-reactive vaccination; what they We demonstrate humoral cell-mediated cross-protection, resulting load OC43 NL63 models. Additionally, present novel non-human primate (NHP) 229E, demonstrating mimics observed humans serve as studies, observed. This significant suggests current vaccines could other part strategy
Language: Английский
Citations
1
bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown
Published: Feb. 28, 2024
1Using computational methods, we designed 60-mer nanoparticles displaying SARS-like betacoronavirus (sarbecovirus) receptor-binding domains (RBDs) by (i) creating RBD sequences with 6 mutations in the SARS-COV-2 WA1 that were predicted to retain proper folding and abrogate antibody responses variable epitopes (mosaic-2COMs; mosaic-5COM), (ii) selecting 7 natural sarbecovirus RBDs (mosaic-7COM). These antigens compared mosaic-8b, which elicits cross-reactive antibodies protects from challenges animals. Immunizations naïve COVID-19 pre-vaccinated mice revealed mosaic-7COM elicited higher binding neutralization titers than mosaic-8b related antigens. Deep mutational scanning showed targeted conserved epitopes. Mosaic-2COMs mosaic-5COM homotypic SARS-CoV-2 Beta RBD-nanoparticles increased potencies against some variants mosaic-7COM. However, more potent zoonotic sarbecoviruses highly mutated Omicrons. results support using protect spillover potential.
Language: Английский
Citations
4
Small, Journal Year: 2024, Volume and Issue: unknown
Published: Nov. 6, 2024
Abstract Subunit vaccines, significant in next‐generation vaccine development, offer precise targeting of immune responses by focusing on specific antigens. However, this precision often comes at the cost eliciting strong and durable immunity, posing a great challenge to design. To address limitation, recent advancements nanoparticles (NPs) are utilized enhance antigen delivery efficiency boost efficacy. This review examines how physicochemical properties NPs influence various stages response during analyzes different NP types contribute activation performance. It then explores unique characteristics mechanisms these NPs, along with their advancements, highlights application subunit vaccines infectious diseases cancer. Finally, it discusses challenges NP‐based development proposes future directions for innovation promising field.
Language: Английский
Citations
4
Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16
Published: May 20, 2025
The Fc regions of antibodies mediate important effector cell functions such as antibody-dependent cellular cytotoxicity (ADCC), phagocytosis (ADCP), neutrophil (ADNP), and complement-dependent (CDC). These enhance immune defense infected clearance. This study evaluated the effect COVID-19 XBB.1.5 booster vaccination on Fc-effector antibody responses to SARS-CoV-2. We developed four assays evaluate SARS-CoV-2 antibodies. ADCC CDC utilized stably transfected luciferase-based target lines expressing spike variants (Ancestral, Wu-1 Omicron XBB.1.5, EG.5) measure antibody-mediated lysis by cells. ADCP ADNP were assessed flow cytometry fluorescently labeled virus-like particles that display variant proteins. Serum samples from 20 healthy adult volunteers pre- post-monovalent vaccine analyzed for pseudovirus neutralizing Prior administration vaccination, cross-neutralizing against EG.5 minimally detectable, while cross-functional present at higher baseline levels. significantly boosted both in magnitude breadth. greatest increase was strain, functional had similar fold-increases titers breadth tested. Neutralizing most highly correlated (prior vaccination) but less post-vaccination, consistent with differential boosting vs monovalent vaccine. improved magnitude, breadth, quality Combining Fc-mediated provides a more comprehensive model understanding vaccine-induced immunity optimizing strategies.
Language: Английский
Citations
0
bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown
Published: March 14, 2024
Abstract Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic betacoronavirus that causes severe and often lethal illness in humans. The MERS-CoV spike (S) protein the viral fusogen target of neutralizing antibodies, has therefore been focus vaccine design efforts. Currently there are no licensed vaccines against only few candidates have advanced to Phase I clinical trials. Here we developed utilizing computationally designed nanoparticle platform generated safe immunogenic various enveloped viruses, including for SARS-CoV-2. Two-component nanoparticles displaying S-derived antigens induced robust antibody responses protected mice challenge with mouse-adapted MERS-CoV. Electron microscopy polyclonal epitope mapping serum competition assays revealed specificities dominant elicited by immunogens prefusion-stabilized S-2P trimer, receptor binding domain (RBD), or N-terminal (NTD). An RBD antibodies targeting multiple non-overlapping epitopes RBD, whereas anti-NTD S-2P– NTD-based converged on single antigenic site. Our findings demonstrate potential two-component suggest this technology could be broadly applicable development.
Language: Английский
Citations
2
Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)
Published: July 27, 2024
Abstract The continued evolution of SARS-CoV-2 underscores the need to understand qualitative aspects humoral immune response elicited by spike immunization. Here, we combine monoclonal antibody (mAb) isolation with deep B cell receptor (BCR) repertoire sequencing rhesus macaques immunized prefusion-stabilized glycoprotein. Longitudinal tracing spike-sorted lineages in multiple compartments demonstrates increasing somatic hypermutation and broad dissemination vaccine-elicited cells draining non-draining lymphoid compartments, including bone marrow, spleen and, most notably, periaortic lymph nodes. Phylogenetic analysis spike-specific identified through delineates extensive intra-clonal diversification that shaped neutralizing activity. Structural complex a broadly mAb provides molecular basis for observed differences neutralization breadth between clonally related antibodies. Our findings highlight immunization leads where members same lineage can both retain original epitope specificity evolve recognize additional variants not previously encountered.
Language: Английский
Citations
2
Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown
Published: Feb. 26, 2024
Language: Английский
Citations
1
iScience, Journal Year: 2024, Volume and Issue: 27(10), P. 110624 - 110624
Published: Aug. 23, 2024
The rapid emergence of SARS-CoV-2 variants concern (VoC) and the threat future zoonotic sarbecovirus spillover emphasizes need for broadly protective next-generation vaccines therapeutics. We utilized spike ferritin nanoparticle (SpFN), receptor binding domain (RFN) immunogens, in an equine model to elicit hyperimmune sera evaluated its neutralization protection capacity. Immunized animals rapidly elicited with potent VoC, SARS-CoV-1 pseudoviruses, against domains from clades 1b, 1a, 2, 3, 4. Purified polyclonal IgG provided Omicron XBB.1.5 virus K18-hACE2 transgenic mouse model. These results suggest that SARS-CoV-2-based can produce a broad response serum has therapeutic potential emerging VoC diverse sarbecoviruses, presenting possible alternative or supplement monoclonal antibody immunotherapies.
Language: Английский
Citations
1
bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown
Published: Sept. 16, 2024
Abstract Development of intranasal vaccines for respiratory viruses has gained popularity. However, currently only a live-attenuated influenza vaccine is FDA-approved administration. Here, we focused on virus as it circulates seasonally, pandemic potential, and formulations that present hemagglutinin (HA) in different structural arrangements. These display differences have not been correlated with induction pan-H1 antibodies or shown to provide protection. Using electron microscopy, biochemistry animal studies, identified HA complexes arranged lipid discs multiple trimeric HAs displayed along the perimeter, termed spike nanobicelles (SNB). We utilized structure-guided approach synthesize vitro assembled spiked (IA-SNB) from classical 1934 H1N1 virus. IA-SNBs elicited provided protection against antigenically divergent via immunizations. Viral glycoprotein spikes SNBs could aid combating antigenic variation innovative universal development.
Language: Английский
Citations
0