Design, Immunogenicity and Preclinical Efficacy of the ChAdOx1.COVconsv12 Pan-Sarbecovirus T-Cell Vaccine.

Design, Immunogenicity and Preclinical Efficacy of the ChAdOx1.COVconsv12 Pan-Sarbecovirus T-Cell Vaccine.

Publication date: Aug 26, 2024

During the COVID-19 pandemic, antibody-based vaccines targeting the SARS-CoV-2 spike glycoprotein were the focus for development because neutralizing antibodies were associated with protection against the SARS-CoV-2 infection pre-clinically and in humans. While deploying these spike-based vaccines saved millions of lives worldwide, it has become clear that the immunological mechanisms of protection against severe disease are multifaceted and involve non-neutralizing antibody components. Here, we describe a novel pan-sarbecovirus T-cell vaccine, ChAdOx1. COVconsv12, designed to complement and broaden the protection of spike vaccines. The vaccine immunogen COVconsv12 employs the two regions in the viral proteome most conserved among sarbecoviruses, which are delivered by replication-deficient vector ChAdOx1. It directs T cells towards epitopes shared among sarbecoviruses including evolving SARS-CoV-2 variants. Here, we show that ChAdOx1. COVconsv12 induced broad T-cell responses in the BALB/c and C57BL/6 mice. In the Syrian hamster challenge model, ChAdOx1. COVconsv12 alone did not protect against the SARS-CoV-2 infection, but when co-administered with 1/50th of the ChAdOx1 nCoV-19 spike vaccine protective dose, faster recovery and lower oral swab viral load were observed. Induction of CD8 T cells may decrease COVID-19 severity and extend the T-cell response coverage of variants to match the known (and as yet unknown) members of the β-coronavirus family.

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Concepts Keywords
Clear ChAdOx1
Covconsv12 challenge
Mice conserved region
Pandemic COVID-19 T cells
Vaccine COVID-19 vaccine
Syrian hamster
T cell vaccine
T cells

Semantics

Type Source Name
disease IDO cell
disease MESH COVID-19 pandemic
pathway REACTOME SARS-CoV-2 Infection
disease IDO replication
disease MESH viral load
disease MESH Retrovirus Infection
drug DRUGBANK Tropicamide
drug DRUGBANK Coenzyme M
disease IDO zoonosis
disease IDO protein
disease MESH infection
disease IDO production
drug DRUGBANK Cefaclor
disease IDO reagent
drug DRUGBANK Tromethamine
drug DRUGBANK Phosphate ion
drug DRUGBANK Alkaline Phosphatase
drug DRUGBANK Streptomycin
disease IDO assay
drug DRUGBANK Collagenase clostridium histolyticum
drug DRUGBANK Amino acids
drug DRUGBANK Dimethyl sulfoxide
disease MESH Infectious Diseases
disease MESH AIDS
drug DRUGBANK Amphotericin B
disease IDO nucleic acid
disease IDO pathogen
disease MESH Viral shedding
drug DRUGBANK Formaldehyde
drug DRUGBANK Ethanol
drug DRUGBANK Water
disease MESH virus infection
drug DRUGBANK Hexocyclium
drug DRUGBANK Methylergometrine
disease IDO blood
drug DRUGBANK L-Valine
disease MESH viremia
disease MESH inflammation
drug DRUGBANK Trestolone
drug DRUGBANK Cysteamine
disease IDO algorithm
disease MESH influenza
disease MESH long COVID
drug DRUGBANK Spinosad
disease IDO infectivity
disease MESH breakthrough infection
drug DRUGBANK Guanosine
disease IDO history
drug DRUGBANK Carboxyamidotriazole
disease MESH Acute Respiratory Distress Syndrome
disease MESH Death
disease MESH Pneumonia
disease IDO host
drug DRUGBANK Telbivudine
drug DRUGBANK Serine

Original Article

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