Immunoinformatics-Based Design of Broad-Spectrum Multi-Epitope Vaccines Targeting Mutations in Emerging SARS-CoV-2 Variants DOI Creative Commons
Xueyin Mei,

Wanrong Xie,

Xue Lin

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 14, 2024

Abstract The ongoing COVID-19 pandemic, intensified by emerging SARS-CoV-2 mutations, highlights the urgent need for enhanced vaccines. Despite considerable efforts in vaccine design, improvements are still required formulating vaccines targeting novel coronavirus. This study, utilized immunoinformatics and reverse vaccinology to design multi-epitope variations. B T cell epitopes were generated analyzing mutation sites of prevalent variant strains, two designed linking with different adjuvants. Interaction model four Toll-like receptors (TLR) revealed a relatively high affinity between immune receptors. Codon optimization computational cloning conducted validate robustness immunogenic simulations performed assess antigenicity antibody generation capability vaccine. L455S JN.1 its adjacent F456L on effectiveness against XBB that 15 structures maintained certain level binding affinity. study offers an immunological evaluation from mutation-centric perspective integrates co-evolutionary analysis effective various strains. methodologies applied this research can also be extended development other pathogens.

Language: Английский

Comparative Analysis of Host Cell Entry Efficiency and Neutralization Sensitivity of Emerging SARS-CoV-2 Lineages KP.2, KP.2.3, KP.3, and LB.1 DOI Creative Commons

Nianzhen Chen,

Katharina Decker,

Sebastian Schulz

et al.

Vaccines, Journal Year: 2024, Volume and Issue: 12(11), P. 1236 - 1236

Published: Oct. 30, 2024

New SARS-CoV-2 lineages continue to evolve and may exhibit new characteristics regarding host cell entry efficiency potential for antibody evasion. Here, employing pseudotyped particles, we compared the efficiency, ACE2 receptor usage, sensitivity antibody-mediated neutralization of four emerging lineages, KP.2, KP.2.3, KP.3, LB.1. The XBB.1.5 JN.1 served as controls. Our findings reveal that LB.1 enter cells efficiently in an ACE2-dependent manner, KP.3 is more adept at entering Calu-3 lung than JN.1. However, variants differed their capacity employ orthologues from animal species entry, suggesting differences interactions. Moreover, demonstrate only two out seven therapeutic monoclonal (mAbs) preclinical development retain robust neutralizing activity against sublineages tested, while three mAbs displayed strongly reduced lacked any tested. Furthermore, our results show evade by antibodies induced infection or vaccination with greater JN.1, particularly individuals without hybrid immunity. This study indicates differ interactions suggest evasion drove emergence these variants.

Language: Английский

Citations

1
Delineating the functional activity of antibodies with cross-reactivity to SARS-CoV-2, SARS-CoV-1 and related sarbecoviruses DOI Open Access
Felicitas Ruiz,

Will Foreman,

Michelle M. Lilly

et al.

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

Published: April 25, 2024

The recurring spillover of pathogenic coronaviruses and demonstrated capacity sarbecoviruses, such SARS-CoV-2, to rapidly evolve in humans underscores the need better understand immune responses this virus family. For purpose, we characterized functional breadth potency antibodies targeting receptor binding domain (RBD) spike glycoprotein that exhibited cross-reactivity against SARS-CoV-2 variants, SARS-CoV-1 sarbecoviruses from diverse clades animal origins with potential. One neutralizing antibody, C68.61, showed remarkable neutralization both variants viruses different sarbecovirus clades. which targets a conserved RBD class 5 epitope, did not select for escape or culture nor have predicted among circulating strains, suggesting epitope is functionally constrained. We identified 11 additional SARS-CoV-2/SARS-CoV-1 cross-reactive target more sequence 4 epitopes within show activity subset one antibody every single tested. A these Fc-mediated effector functions as potent impact infection outcome models. Thus, our study regions across may serve therapeutics pandemic preparedness well blueprints design immunogens capable eliciting cross-neutralizing responses.

Language: Английский

Citations

0
Enhanced Reverse Zoonotic Potential and Immune Evasion by Omicron JN.1 Variant DOI
Jiaxin Hu,

Fuwen Zan,

Xiuyuan Ou

et al.

Published: Jan. 1, 2024

Language: Английский

Citations

0
Wastewater Surveillance of SARS-CoV-2 in Zambia: An Early Warning Tool DOI Open Access
Doreen Mainza Shempela, Walter Muleya, Steward Mudenda

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(16), P. 8839 - 8839

Published: Aug. 14, 2024

Wastewater-based surveillance has emerged as an important method for monitoring the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). This study investigated presence of SARS-CoV-2 in wastewater Zambia. We conducted a longitudinal Copperbelt and Eastern provinces Zambia from October 2023 to December during which 155 samples were collected. The subjected three different concentration methods, namely bag-mediated filtration, skimmed milk flocculation, polythene glycol-based assays. Molecular detection nucleic acid was using real-time Polymerase Chain Reaction (PCR). Whole genome sequencing Illumina COVIDSEQ assay. Of samples, 62 (40%) tested positive SARS-CoV-2. these, 13 sequences sufficient length determine lineages obtained phylogenetically analyzed. Various Omicron subvariants detected including BA.5, XBB.1.45, BA.2.86, JN.1. Some these have been clinical cases Interestingly, phylogenetic analysis positioned sequence Province B.1.1.529 clade, suggesting that earlier variants late 2021 could still be circulating may not wholly replaced by newer subvariants. stresses need integrating into mainstream strategies circulation

Language: Английский

Citations

0
Immunoinformatics-Based Design of Broad-Spectrum Multi-Epitope Vaccines Targeting Mutations in Emerging SARS-CoV-2 Variants DOI Creative Commons
Xueyin Mei,

Wanrong Xie,

Xue Lin

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 14, 2024

Abstract The ongoing COVID-19 pandemic, intensified by emerging SARS-CoV-2 mutations, highlights the urgent need for enhanced vaccines. Despite considerable efforts in vaccine design, improvements are still required formulating vaccines targeting novel coronavirus. This study, utilized immunoinformatics and reverse vaccinology to design multi-epitope variations. B T cell epitopes were generated analyzing mutation sites of prevalent variant strains, two designed linking with different adjuvants. Interaction model four Toll-like receptors (TLR) revealed a relatively high affinity between immune receptors. Codon optimization computational cloning conducted validate robustness immunogenic simulations performed assess antigenicity antibody generation capability vaccine. L455S JN.1 its adjacent F456L on effectiveness against XBB that 15 structures maintained certain level binding affinity. study offers an immunological evaluation from mutation-centric perspective integrates co-evolutionary analysis effective various strains. methodologies applied this research can also be extended development other pathogens.

Language: Английский

Citations

0