RNA vaccines against infectious diseases
Inventors
Reed, Steven Gregory • Carter, Darrick Albert • Khandhar, Amit Praful • Archer, Jacob Freeman • Berglund, Lars Peter Aksel • Erasmus, Jesse • Berube, Bryan • Duthie, Malcolm S.
Assignees
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Publication Number
US-12350329-B2
Publication Date
2025-07-08
Expiration Date
Abstract
The disclosure provides compositions, methods of treatment, and methods of making and using compositions to deliver a nucleic acid to a subject. Methods of using these compositions as a vaccine for treatment of an infectious disease are also provided.
Core Innovation
The invention provides RNA vaccine compositions that include nucleic acids encoding an antigen from an influenza virus. The influenza antigen sequence is at least 85% identical to SEQ ID NO: 3, and the nucleic acids are formulated with a lipid carrier comprising liquid oil, a cationic lipid, a hydrophilic surfactant, and a hydrophobic surfactant.
The compositions also include nucleic acids encoding additional antigens from infectious pathogens. The disclosed antigen payloads include influenza hemagglutinin stem and VZV gE variants, and the nucleic acids can include sequences related to a VEEV RNA polymerase as an encoded element.
The lipid-carrier and nanoemulsion system is further disclosed as optionally including inorganic nanoparticles and additional excipients, including oleic-acid-coated iron oxide nanoparticles. The document describes formulation and solid-state forms including lyophilized or spray-dried compositions, together with cryoprotectants for thermal stability.
Claims Coverage
The independent claim covers an RNA vaccine composition with a lipid carrier comprising liquid oil, a cationic lipid, a hydrophilic surfactant, and a hydrophobic surfactant, together with influenza nucleic acids at least 85% identical to SEQ ID NO: 3. Dependent claims add surfactant selections, nucleic-acid amount constraints, sequence specification for RNA polymerase, and optional inorganic particle metal-oxide options.
Lipid carrier with liquid oil, cationic lipid, hydrophilic surfactant, and hydrophobic surfactant
A composition comprising a lipid carrier wherein the lipid carrier comprises liquid oil, a cationic lipid, a hydrophilic surfactant, and a hydrophobic surfactant.
Influenza antigen nucleic acid sequence identity
The nucleic acids comprise a sequence encoding for an antigen from an influenza virus, wherein the sequence is at least 85% identical to SEQ ID NO: 3.
Nucleic acids amount constraint
The nucleic acids are present in an amount up to about 5, about 10, about 25, about 50, or about 100 micrograms (µg).
Hydrophobic surfactant selection
The hydrophobic surfactant is one of sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, sorbitan monooleate, or sorbitan trioleate.
Hydrophilic surfactant selection
The hydrophilic surfactant is a polysorbate.
RNA polymerase sequence specification
The nucleic acids encoding the RNA polymerase include the sequence identified as SEQ ID NO: 34.
Metal oxide options for inorganic particles
The metal oxide comprises one or more of aluminum oxide, aluminum oxyhydroxide, iron oxide, titanium dioxide, or silicon dioxide.
Overall, the claim set is centered on an RNA vaccine composition using a defined lipid-carrier component set together with influenza antigen nucleic acids having at least 85% identity to SEQ ID NO: 3, while dependent claims narrow surfactant identities, constrain nucleic-acid amount, specify an RNA polymerase sequence by SEQ ID NO: 34, and optionally define inorganic metal-oxide options.
Stated Advantages
Higher protein with reduced TNF-alpha stimulation for a compared lipid-carrier condition (miglyol).
Documented Applications
Evaluation of innate immune responses and protein expression using self-replicating RNA delivered by multiple lipid-carrier formulations, with luciferase and TNF-alpha readouts.
mRNA vaccine formulation use cases including liquid and lyophilized mRNA vaccine formats with antigen encoding sequences, along with in vitro expression and in vivo immunization readouts using ELISA antibody titers.
Self-replicating RNA construct use cases including VZV repRNA constructs with gE/gI variations, with in vitro expression and in vivo immunization assessed by ELISA against soluble VZV gE.
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