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

Post-pandemic memory T cell response to SARS-CoV-2 is durable, broadly targeted, and cross-reactive to the hypermutated BA.2.86 variant DOI Creative Commons

Rofhiwa Nesamari,

Millicent A. Omondi, Richard Baguma

и другие.

Cell Host & Microbe, Год журнала: 2024, Номер 32(2), С. 162 - 169.e3

Опубликована: Янв. 10, 2024

Ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolution has given rise to recombinant Omicron lineages that dominate globally (XBB.1), as well the emergence of hypermutated variants (BA.2.86). In this context, durable and cross-reactive T cell immune memory is critical for continued protection against COVID-19. We examined responses SARS-CoV-2 approximately 1.5 years since first emerged. describe sustained CD4+ CD8+ spike-specific in healthcare workers South Africa (n = 39) who were vaccinated experienced at least one infection. Spike-specific cells are highly with all tested, including BA.2.86. Abundant nucleocapsid membrane-specific detectable most participants. The bulk SARS-CoV-2-specific have an early-differentiated phenotype, explaining their persistent nature. Overall, hybrid immunity leads accumulation spike non-spike evident 3.5 after start pandemic, preserved recognition mutated variants.

Язык: Английский

Процитировано

31
mRNA-LNP vaccine-induced CD8+ T cells protect mice from lethal SARS-CoV-2 infection in the absence of specific antibodies DOI Creative Commons
Brian Montoya, Carolina R. Melo‐Silva, Lingjuan Tang

и другие.

Molecular Therapy, Год журнала: 2024, Номер 32(6), С. 1790 - 1804

Опубликована: Апрель 11, 2024

The role of CD8

Язык: Английский

Процитировано

5
UB-612 pan-SARS-CoV-2 T cell immunity-promoting vaccine protects against COVID-19 moderate-severe disease DOI Creative Commons
Chang Yi Wang,

Be-Sheng Kuo,

Yu-Hsiang Lee

и другие.

iScience, Год журнала: 2024, Номер 27(2), С. 108887 - 108887

Опубликована: Янв. 20, 2024

Язык: Английский

Процитировано

4
Revisiting the dimensions of universal vaccine with special focus on COVID-19: Efficacy versus methods of designing DOI

Puja Jaishwal,

Kisalay Jha,

Satarudra Prakash Singh

и другие.

International Journal of Biological Macromolecules, Год журнала: 2024, Номер 277, С. 134012 - 134012

Опубликована: Июль 22, 2024

Язык: Английский

Процитировано

4
Bioinformatic identification of Conserved epitopes from SARS-COV-2 genome isolated in Kenya DOI

Elius Mbogori,

Stanslaus Musyoki,

Richard Biegon

и другие.

Next research., Год журнала: 2025, Номер unknown, С. 100215 - 100215

Опубликована: Фев. 1, 2025

Язык: Английский

Процитировано

0
Reverse vaccinology-based multi-epitope COVID-19 vaccine targeting SARS-CoV-2 structural and non-structural proteins induces immune responses in mice DOI Creative Commons
Azzania Fibriani, Nicholas Yamahoki, Adi Shani

и другие.

Vaccine X, Год журнала: 2025, Номер unknown, С. 100632 - 100632

Опубликована: Март 1, 2025

Язык: Английский

Процитировано

0
Rerouting therapeutic peptides and unlocking their potential against SARS-CoV2 DOI

Namrata Prashar,

Sameer Khairullah MOHAMMED,

Raja Natesan Sella

и другие.

3 Biotech, Год журнала: 2025, Номер 15(5)

Опубликована: Апрель 4, 2025

Язык: Английский

Процитировано

0
Beyond the Pandemic Era: Recent Advances and Efficacy of SARS-CoV-2 Vaccines Against Emerging Variants of Concern DOI Creative Commons
Ankita Saha, Sounak Ghosh Roy, Richa Dwivedi

и другие.

Vaccines, Год журнала: 2025, Номер 13(4), С. 424 - 424

Опубликована: Апрель 17, 2025

Vaccination has been instrumental in curbing the transmission of SARS-CoV-2 and mitigating severity clinical manifestations associated with COVID-19. Numerous COVID-19 vaccines have developed to this effect, including BioNTech-Pfizer Moderna’s mRNA vaccines, as well adenovirus vector-based such Oxford–AstraZeneca. However, emergence new variants subvariants SARS-CoV-2, characterized by enhanced transmissibility immune evasion, poses significant challenges efficacy current vaccination strategies. In review, we aim comprehensively outline landscape emerging concern (VOCs) sub-lineages that recently surfaced post-pandemic years. We assess effectiveness existing their booster doses, against these subvariants, BA.2-derived sub-lineages, XBB BA.2.86 (Pirola). Furthermore, discuss latest advancements vaccine technology, multivalent pan-coronavirus approaches, along development several next-generation coronavirus exosome-based, virus-like particle (VLP), mucosal, nanomaterial-based vaccines. Finally, highlight key critical areas for future research address evolving threat develop strategies combating viral threats, thereby improving preparedness pandemics.

Язык: Английский

Процитировано

0
Broad protective RBD heterotrimer vaccines neutralize SARS-CoV-2 including Omicron sub-variants XBB/BQ.1.1/BF.7 DOI Creative Commons
Yanfang Zhang, Xinrui Kang, Sheng Liu

и другие.

PLoS Pathogens, Год журнала: 2023, Номер 19(9), С. e1011659 - e1011659

Опубликована: Сен. 18, 2023

SARS-CoV-2 variants with severe immune evasion are a major challenge for COVID-19 prevention, especially the circulating Omicron XBB/BQ.1.1/BF.7 strains. Thus, next-generation of broad-spectrum vaccines urgently needed. Previously, we developed protein subunit vaccine, ZF2001, based on RBD-homodimer as immunogen. To adapt variants, chimeric RBD-heterodimers to induce broad responses. In this study, further explored concept tandem RBD homotrimer and heterotrimer. Prototype RBD-homotrimer, prototype-Delta-BA.1 (PDO) RBD-heterotrimer Delta-BA.2-BA.5 (DBA2BA5) were designed. Biochemical cryo-EM structural characterization demonstrated total epitope exposure RBD-trimers. mouse experiments, PDO DBA2BA5 elicited neutralization. Potent protection against was observed in assays correlated neutralizing antibody titer. This study validated design strategy RBD-heterotrimers multivalent immunogens presented promising vaccine candidate, DBA2BA5, eliciting responses, including XBB/BF.7/BQ.1.1.

Язык: Английский

Процитировано

8
Boosting PRRSV-Specific Cellular Immunity: The Immunological Profiling of an Fc-Fused Multi-CTL Epitope Vaccine in Mice DOI Creative Commons
Xinnuo Lei,

Jinzhao Ban,

Zhi Wu

и другие.

Veterinary Sciences, Год журнала: 2024, Номер 11(6), С. 274 - 274

Опубликована: Июнь 15, 2024

The continuously evolving PRRSV has been plaguing pig farms worldwide for over 30 years, with conventional vaccines suffering from insufficient protection and biosecurity risks. To address these challenges, we identified 10 PRRSV-specific CTL epitopes through enzyme-linked immunospot assay (ELISPOT) constructed a multi-epitope peptide (PTE) by linking them in tandem. This PTE was then fused modified porcine Fc molecule to create the recombinant protein pFc-PTE. Our findings indicate that pFc-PTE effectively stimulates PRRSV-infected specific splenic lymphocytes secrete high levels of interferon-gamma (IFN-γ) is predicted be non-toxic non-allergenic. Compared alone, not only induced comparable cellular immune response mice but also extended duration at least weeks post-immunization. Additionally, predominantly Th1 response, suggesting its potential advantage enhancing immunity. Consequently, holds promise as novel, safe, potent candidate vaccine may provide new perspectives design against other viral diseases.

Язык: Английский

Процитировано

2