A lung-selective delivery of mRNA encoding broadly neutralizing antibody against SARS-CoV-2 infection.

Publication date: Dec 05, 2023

The respiratory system, especially the lung, is the key site of pathological injury induced by SARS-CoV-2 infection. Given the low feasibility of targeted delivery of antibodies into the lungs by intravenous administration and the short half-life period of antibodies in the lungs by intranasal or aerosolized immunization, mRNA encoding broadly neutralizing antibodies with lung-targeting capability can perfectly provide high-titer antibodies in lungs to prevent the SARS-CoV-2 infection. Here, we firstly identify a human monoclonal antibody, 8-9D, with broad neutralizing potency against SARS-CoV-2 variants. The neutralization mechanism of this antibody is explained by the structural characteristics of 8-9D Fabs in complex with the Omicron BA. 5 spike. In addition, we evaluate the efficacy of 8-9D using a safe and robust mRNA delivery platform and compare the performance of 8-9D when its mRNA is and is not selectively delivered to the lungs. The lung-selective delivery of the 8-9D mRNA enables the expression of neutralizing antibodies in the lungs which blocks the invasion of the virus, thus effectively protecting female K18-hACE2 transgenic mice from challenge with the Beta or Omicron BA. 1 variant. Our work underscores the potential application of lung-selective mRNA antibodies in the prevention and treatment of infections caused by circulating SARS-CoV-2 variants.

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Concepts Keywords
Aerosolized 9d
Antibodies Antibodies
Immunization Antibody
Mrna Cov
Short Delivery
Encoding
Infection
Lung
Lungs
Mrna
Neutralizing
Omicron
Sars
Selective
Variants

Semantics

Type Source Name
disease MESH SARS-CoV-2 infection
pathway REACTOME SARS-CoV-2 Infection
disease IDO site
disease VO immunization
disease VO titer
disease MESH infections
disease MESH death
disease MESH Infectious Diseases
drug DRUGBANK Phosphorus
drug DRUGBANK Coenzyme M
disease MESH emerging infectious diseases
drug DRUGBANK Trestolone
disease VO passive immunization
disease VO effectiveness
disease VO vaccination
disease MESH emergency
disease VO vaccine
disease MESH influenza
disease MESH rabies
drug DRUGBANK Spinosad
disease IDO pathogen
disease IDO production
disease VO organ
disease IDO infection
disease VO efficient
disease VO inactivated vaccine
disease VO immunized
disease IDO assay
disease MESH dissociation
drug DRUGBANK Angiotensin II
drug DRUGBANK Aspartame
disease VO efficiency
disease IDO infectivity
drug DRUGBANK Cholesterol
drug DRUGBANK Polyethylene glycol
disease VO effective
drug DRUGBANK Iodide
drug DRUGBANK Ethanol
drug DRUGBANK Tretamine
drug DRUGBANK Phosphate ion
disease VO injection
drug DRUGBANK L-Alanine
drug DRUGBANK Uric Acid
disease IDO blood
drug DRUGBANK Urea
drug DRUGBANK Nitrogen
drug DRUGBANK Creatinine
disease VO dose
drug DRUGBANK Isoxaflutole
drug DRUGBANK Oxygen
disease MESH hemolysis
pathway KEGG Viral replication
disease IDO host
disease IDO susceptibility
disease MESH respiratory diseases
disease MESH pulmonary embolism
disease VO stomach
disease VO Respiratory syncytial virus
disease VO Viruses
disease VO protocol
disease IDO cell
drug DRUGBANK Edetic Acid
drug DRUGBANK Flunarizine
drug DRUGBANK Dimethyl sulfoxide
drug DRUGBANK Cysteamine
drug DRUGBANK Cefaclor
disease VO vaccinated
disease VO ANOVA
drug DRUGBANK Glycine
drug DRUGBANK Papain
drug DRUGBANK Amino acids
drug DRUGBANK Glycerin
drug DRUGBANK Activated charcoal
drug DRUGBANK Titanium
disease VO company
drug DRUGBANK Tromethamine
drug DRUGBANK Acetate ion
drug DRUGBANK Water
drug DRUGBANK Sodium lauryl sulfate
drug DRUGBANK Methylergometrine
drug DRUGBANK Oleic Acid
drug DRUGBANK N N-dimethylformamide
drug DRUGBANK Toluene
drug DRUGBANK Oleoyl chloride
drug DRUGBANK Trolamine
disease VO volume
drug DRUGBANK Copper
drug DRUGBANK Ademetionine
disease VO viability
drug DRUGBANK Hyaluronic acid
disease VO USA
drug DRUGBANK Carbonate ion
disease IDO colony
disease VO dead
disease IDO symptom
disease MESH Zoonoses
drug DRUGBANK (S)-Des-Me-Ampa
disease MESH viral infections
disease MESH monkeypox
disease MESH parasitic infections
disease VO vaccine candidate
disease VO Env
disease VO Gag
disease VO Optaflu
drug DRUGBANK D-Alanine
drug DRUGBANK Tricyclazole
disease VO time
disease MESH Vector borne Diseases

Original Article

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