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

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: June 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.

Language: 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

et al.

Cell Host & Microbe, Journal Year: 2024, Volume and Issue: 32(2), P. 162 - 169.e3

Published: Jan. 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.

Language: Английский

Citations

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

et al.

Molecular Therapy, Journal Year: 2024, Volume and Issue: 32(6), P. 1790 - 1804

Published: April 11, 2024

The role of CD8

Language: Английский

Citations

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

et al.

iScience, Journal Year: 2024, Volume and Issue: 27(2), P. 108887 - 108887

Published: Jan. 20, 2024

Language: Английский

Citations

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

et al.

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 277, P. 134012 - 134012

Published: July 22, 2024

Language: Английский

Citations

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

Elius Mbogori,

Stanslaus Musyoki,

Richard Biegon

et al.

Next research., Journal Year: 2025, Volume and Issue: unknown, P. 100215 - 100215

Published: Feb. 1, 2025

Language: Английский

Citations

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

et al.

Vaccine X, Journal Year: 2025, Volume and Issue: unknown, P. 100632 - 100632

Published: March 1, 2025

Language: Английский

Citations

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

Namrata Prashar,

Sameer Khairullah MOHAMMED,

Raja Natesan Sella

et al.

3 Biotech, Journal Year: 2025, Volume and Issue: 15(5)

Published: April 4, 2025

Language: Английский

Citations

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

et al.

Vaccines, Journal Year: 2025, Volume and Issue: 13(4), P. 424 - 424

Published: April 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.

Language: Английский

Citations

0
The Immunogenicity of CpG, MF59-Like, and Alum Adjuvant Delta Strain Inactivated SARS-CoV-2 Vaccines in Mice DOI Creative Commons
Kangwei Xu, Jing Li,

Lu Xu

et al.

Vaccines, Journal Year: 2024, Volume and Issue: 12(1), P. 60 - 60

Published: Jan. 7, 2024

The continuous evolution and mutation of SARS-CoV-2 have highlighted the need for more effective vaccines. In this study, CpG, MF59-like, Alum adjuvant Delta strain inactivated vaccines were prepared, immunogenicity these in mice was evaluated. + MF59-like vaccine group produced highest levels S- RBD-binding antibodies live virus neutralization after one shot immunization, while had two doses, groups high cross-neutralization against prototype, Beta, Gamma viruses. There no significant decrease neutralizing antibody any during observation period. excited different subtypes compared with unadjuvanted vaccines; CpG a higher proportion IgG2b antibodies, indicating bias towards Th1 immunity. proportions IgG1 similar to those vaccine. However, Th2 Antigen-specific cytokine secretion CD4/8+ T cells analyzed. conclusion, results study show differences immune efficacy mice, which implications selection strategy adjuvants.

Language: Английский

Citations

3
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

et al.

PLoS Pathogens, Journal Year: 2023, Volume and Issue: 19(9), P. e1011659 - e1011659

Published: Sept. 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.

Language: Английский

Citations

8