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Targeting Multiple Conserved T-Cell Epitopes for Protection against COVID-19 Moderate-Severe Disease by a Pan-Sarbecovirus Vaccine (preprint)
medrxiv; 2023.
Preprint
in English
| medRxiv | ID: ppzbmed-10.1101.2023.06.28.23291948
ABSTRACT
Background Most of current approved vaccines, based on a Spike-only as single immunogen, fall short of producing a full-blown T-cell immunity. SARS-CoV-2 continues to evolve with ever-emergent higher-contagious mutants that may take a turn going beyond Omicron to bring about a new pandemic outbreak. New recombinant SARS-CoV-2 species could be man-made through genetic manipulation to infect systemically. Development of composition-innovated, pan-variant COVID-19 vaccines to prevent from hospitalization and severe disease, and to forestall the next pandemic catastrophe, is an urgent global objective. Methods and findings In a retrospective, e-questionnaire Observational Study, extended from a clinical Phase-2 trial conducted in Taiwan, during the prime time of Omicron outbreak dominated by BA.2 and BA.5 variants, we investigated the preventive effects against COVID-19 moderate-severe disease (hospitalization and ICU admission) by a pan-Sarbecovirus vaccine UB-612 that targets monomeric S1-RBD-focused subunit protein and five designer peptides comprising sequence-conserved, non-mutable helper and cytotoxic T lymphocyte (Th/CTL) epitopes derived from Spike (S2), Membrane (M) and Nucleocapsid (N) proteins. Per UB-612 vaccination, there were no hospitalization and ICU admission cases (0% rate, 6 months after Omicron outbreak) reported [≥]14 months post-2nd dose of primary series, and [≥]10 months post-booster (3rd dose), to which the potent memory cytotoxic CD8 T cell immunity may be the pivotal in control of the infection disease severity. Six months post-booster, the infection rate (asymptomatic and symptomatic mild) was only 1.2%, which increased to 27.8% observed [≥]10 months post-booster. The notable protection effects are in good alignment with a preliminary Phase-3 heterologous booster trial report showing that UB-612 can serve as a competent booster substitute for other EUA-approved vaccine platforms to enhance their seroconversion rate and viral-neutralizing titer against Omicron BA.5. Conclusions UB-612, a universal multitope vaccine promoting full-blown T cell immunity, may work as a competent primer and booster for persons vulnerable to Sarbecovirus infection. Trial Registration. Clinical Trials.gov ID NCT04773067.
Full text:
Available
Collection:
Preprints
Database:
medRxiv
Main subject:
COVID-19
/
Infections
Language:
English
Year:
2023
Document Type:
Preprint
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