Targeting Multiple Conserved T-Cell Epitopes for Protection against COVID-19 Moderate-Severe Disease by a Pan-Sarbecovirus Vaccine DOI Creative Commons

Chang Yi Wang,

Be-Sheng Kuo,

Yu‐Hsiang Lee

и другие.

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

Опубликована: Июнь 28, 2023

ABSTRACT Background Most of current approved vaccines, based on a Spike-only as single immunogen, fall short producing full-blown T-cell immunity. SARS-CoV-2 continues to evolve with ever-emergent higher-contagious mutants that may take turn going beyond Omicron bring about new pandemic outbreak. New recombinant species could be man-made through genetic manipulation infect systemically. Development composition-innovated, pan-variant COVID-19 vaccines prevent from hospitalization and severe disease, forestall the next catastrophe, is an urgent global objective. Methods findings In retrospective, e-questionnaire Observational Study, extended clinical Phase-2 trial conducted in Taiwan, during prime time outbreak dominated by BA.2 BA.5 variants, we investigated preventive effects against moderate-severe disease (hospitalization ICU admission) pan-Sarbecovirus vaccine UB-612 targets monomeric S1-RBD-focused subunit protein five designer peptides comprising sequence-conserved, non-mutable helper cytotoxic T lymphocyte (Th/CTL) epitopes derived Spike (S2), Membrane (M) Nucleocapsid (N) proteins. Per vaccination, there were no admission cases (0% rate, 6 months after outbreak) reported ≥14 post-2 nd dose primary series, ≥10 post-booster (3 rd dose), which potent memory CD8 cell immunity pivotal control infection severity. Six post-booster, rate (asymptomatic symptomatic mild) was only 1.2%, increased 27.8% observed post-booster. The notable protection are good alignment preliminary Phase-3 heterologous booster report showing can serve competent substitute for other EUA-approved platforms enhance their seroconversion viral-neutralizing titer BA.5. Conclusions UB-612, universal multitope promoting immunity, work primer persons vulnerable Sarbecovirus infection. Trial Registration ClinicalTrials.gov ID: NCT04773067 . AUTHOR SUMMARY A immunogen would full-blown, escape-proof era plagued ever-evolving mutants, immune antibodies variants seen cliff drop, rendering strength increasingly less relevant parameter. true, issue at heart development has not been updating variant component increase antibody prevention infection, but validate have potential head off hospitalization, ultimately reinfection altogether, so catastrophe To reach ideal goals, able produce potent, broadly recognizing durable essential. immunity-promoting mutitope vaccine, shown provide strong long-lasting month protective effect admission). unique S1-RBD armed sequence-conserved (S2×3), proteins across species.

Язык: Английский

Identification of potential antigenic proteins and epitopes for the development of a monkeypox virus vaccine: an in silico approach DOI

Emre Aktaş,

Uğur Sezerman, Murat Özer

и другие.

Molecular Diversity, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 15, 2024

Язык: Английский

Процитировано

0
Comparison of a SARS-CoV-2 mRNA booster immunization containing additional antigens to a spike-based mRNA vaccine against Omicron BA.5 infection in hACE2 mice DOI Creative Commons
Jacklyn R. Hurst,

Maedeh Naghibosadat,

Patrick Budowski

и другие.

PLoS ONE, Год журнала: 2024, Номер 19(12), С. e0314061 - e0314061

Опубликована: Дек. 3, 2024

The emergence of SARS-CoV-2 variants presents challenges to vaccine effectiveness, underlining the necessity for next-generation vaccines with multiple antigens beyond spike protein. Here, we investigated a multiantigenic booster containing and chimeric construct composed nucleoprotein (N) membrane (M) proteins, comparing its efficacy spike-only against Omicron BA.5 in K18-hACE2 mice. Initially, mice were primed boosted Beta (B.1.351) mRNA, showing strong spike-specific T cell responses neutralizing antibodies, albeit limited cross-neutralization variants. Subsequently, spike-NM was then examined as second dose protection hACE2-transgenic Mice receiving either homologous or heterologous had nearly complete inhibition infectious virus shedding oral swabs reduced viral burdens both lung nasal tissues following challenge. Examination pathology further revealed that boosters provided comparable inflammatory infiltrates fibrosis. Moreover, demonstrated neutralization pseudovirus assay Wuhan-Hu-1, Beta, akin booster. These findings indicate supplementing additional targets immunization confers equivalent immunity BA.5. This work highlights promising strategy individuals previously vaccinated vaccines, potentially offering enhanced emerging coronaviruses.

Язык: Английский

Процитировано

0
A Universal Multi-Epitope Vaccine Design Against Porcine Reproductive and Respiratory Syndrome Virus via Bioinformatics and Immunoinformatics Approaches DOI Creative Commons
Xinnuo Lei, Zhi Wu, Qi Feng

и другие.

Veterinary Sciences, Год журнала: 2024, Номер 11(12), С. 659 - 659

Опубликована: Дек. 16, 2024

Porcine reproductive and respiratory syndrome virus (PRRSV) causes disorders in sows severe pneumonia piglets, alongside immunosuppressive effects on the host. It poses a significant global threat to swine industry, with no effective control measures currently available due its complex pathogenesis high variability. Conventional inactivated attenuated vaccines provide inadequate protection carry biosafety risks. In this study, we designed universal multi-epitope peptide vaccine against PRRSV using bioinformatics immunoinformatics approaches address these limitations. By selecting sequences from seven representative strains, predicted highly conserved immunogenic T cell (Th CTL) epitopes across all encoded proteins. These were rationally concatenated reported B neutralizing into construct. We performed comprehensive assessments of construct’s physicochemical biochemical properties, along predictions refinements secondary tertiary structures. Molecular docking simulations TLR2 TLR4 revealed strong potential binding interactions. Immune indicated that could induce robust humoral cellular immune responses. This study provides scientific foundation for development safe subunit offers new perspectives designing other viral diseases.

Язык: Английский

Процитировано

0
The Quantification of Spike Proteins in the Inactivated SARS-CoV-2 Vaccines of the Prototype, Delta, and Omicron Variants by LC–MS DOI Creative Commons
Kangwei Xu, Huang Sun,

Kaiqin Wang

и другие.

Vaccines, Год журнала: 2023, Номер 11(5), С. 1002 - 1002

Опубликована: Май 20, 2023

Developing variant vaccines or multivalent is a feasible way to address the epidemic as SARS-CoV-2 variants of concern (VOCs) posed an increased risk global public health. The spike protein virus was usually used main antigen in many types produce neutralizing antibodies against virus. However, (S) proteins different were only differentiated by few amino acids, making it difficult obtain specific that can distinguish VOCs, thereby challenging accurate distinction and quantification using immunological methods such ELISA. Here, we established method based on LC-MS quantify S inactivated monovalent trivalent (prototype, Delta, Omicron strains). By analyzing sequences prototype, strains, identified peptides among three strains synthesized them references. synthetic isotopically labeled internal targets. Quantitative analysis performed calculating ratio between reference target. verification results have shown had good specificity, accuracy, precision. This not accurately vaccine but also could be applied each strain vaccines. Hence, this study quality control variation enabling more quantification, will help improve protection some extent.

Язык: Английский

Процитировано

1
Targeting Multiple Conserved T-Cell Epitopes for Protection against COVID-19 Moderate-Severe Disease by a Pan-Sarbecovirus Vaccine DOI Creative Commons

Chang Yi Wang,

Be-Sheng Kuo,

Yu‐Hsiang Lee

и другие.

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

Опубликована: Июнь 28, 2023

ABSTRACT Background Most of current approved vaccines, based on a Spike-only as single immunogen, fall short producing full-blown T-cell immunity. SARS-CoV-2 continues to evolve with ever-emergent higher-contagious mutants that may take turn going beyond Omicron bring about new pandemic outbreak. New recombinant species could be man-made through genetic manipulation infect systemically. Development composition-innovated, pan-variant COVID-19 vaccines prevent from hospitalization and severe disease, forestall the next catastrophe, is an urgent global objective. Methods findings In retrospective, e-questionnaire Observational Study, extended clinical Phase-2 trial conducted in Taiwan, during prime time outbreak dominated by BA.2 BA.5 variants, we investigated preventive effects against moderate-severe disease (hospitalization ICU admission) pan-Sarbecovirus vaccine UB-612 targets monomeric S1-RBD-focused subunit protein five designer peptides comprising sequence-conserved, non-mutable helper cytotoxic T lymphocyte (Th/CTL) epitopes derived Spike (S2), Membrane (M) Nucleocapsid (N) proteins. Per vaccination, there were no admission cases (0% rate, 6 months after outbreak) reported ≥14 post-2 nd dose primary series, ≥10 post-booster (3 rd dose), which potent memory CD8 cell immunity pivotal control infection severity. Six post-booster, rate (asymptomatic symptomatic mild) was only 1.2%, increased 27.8% observed post-booster. The notable protection are good alignment preliminary Phase-3 heterologous booster report showing can serve competent substitute for other EUA-approved platforms enhance their seroconversion viral-neutralizing titer BA.5. Conclusions UB-612, universal multitope promoting immunity, work primer persons vulnerable Sarbecovirus infection. Trial Registration ClinicalTrials.gov ID: NCT04773067 . AUTHOR SUMMARY A immunogen would full-blown, escape-proof era plagued ever-evolving mutants, immune antibodies variants seen cliff drop, rendering strength increasingly less relevant parameter. true, issue at heart development has not been updating variant component increase antibody prevention infection, but validate have potential head off hospitalization, ultimately reinfection altogether, so catastrophe To reach ideal goals, able produce potent, broadly recognizing durable essential. immunity-promoting mutitope vaccine, shown provide strong long-lasting month protective effect admission). unique S1-RBD armed sequence-conserved (S2×3), proteins across species.

Язык: Английский

Процитировано

0