Methods of using low dose volume B-cell epitope compositions for inducing an antibody immune response in human subjects
Inventors
Mansour, Marc • Ors, Frederic • Stanford, Marianne • Sammatur, Leeladhar • Rajagopalan, Rajkannan • MacDonald, Lisa Diana
Assignees
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Publication Number
US-12042537-B2
Publication Date
2024-07-23
Expiration Date
Abstract
The present disclosure provides methods, uses and compositions and kits for use in inducing an antibody immune response in a human subject. The methods and uses involve administering parenterally a low dose volume of a composition comprising an antigen comprising a B-cell epitope, an amphipathic compound, and a hydrophobic carrier, wherein the low dose volume of the composition is less than 100 μl and induces an antibody immune response to the B-cell epitope in the human subject.
Core Innovation
The invention relates to inducing an antibody immune response in a human subject by parenterally administering a low dose volume of a composition comprising an antigen comprising a B-cell epitope, an amphipathic compound, and a hydrophobic carrier. The low dose volume is less than 100 μL, and the composition is described as a low-dose-volume format for eliciting antibody immune responses to the B-cell epitope.
The disclosed compositions use a hydrophobic carrier in an oil-based or water-free or substantially water-free composition, in which an amphipathic compound and the antigen are provided together with the hydrophobic carrier. The described amphipathic and carrier components include lipid components such as DOPC and cholesterol together with oil-based carriers including mineral oil and Montanide® ISA 51 VG, configured as a low-dose-volume parenteral formulation.
In examples focused on respiratory syncytial virus small hydrophobic ectodomain (RSV SHe), the antigen includes B-cell epitope peptides corresponding to SHeA and SHeB (SEQ ID NO:1 and 2). The compositions are also described as including a lipopeptide adjuvant (PAM3Cys-Ser-(Lys)4; SEQ ID NO:3) formulated with an oil-based carrier and an amphipathic lipid system such as DOPC/cholesterol. The disclosed data report human antibody titers following oil-based low-volume dosing and show antibody responses that persist to at least Day 84 or Day 236, with acceptable safety as described.
Claims Coverage
The independent claims cover three core aspects: a method of inducing an antibody immune response in a human subject using a parenteral low-dose-volume composition; a low-dose-volume composition itself for parenteral administration; and a kit containing that low-dose composition. Across the independent claims, the claims are organized around three inventive features: an antigen comprising a B-cell epitope, an amphipathic compound, and a hydrophobic carrier, delivered at a low dose volume of less than 100 μL.
Parenteral low-dose-volume induction of antibody response to a B-cell epitope
A method for inducing an antibody immune response in a human subject by administering parenterally a low dose volume composition that comprises an antigen comprising a B-cell epitope, an amphipathic compound, and a hydrophobic carrier, where the low dose volume is less than 100 μL and induces an antibody immune response to the B-cell epitope.
Low dose volume composition for parenteral administration
A low dose volume of a composition comprising an antigen comprising a B-cell epitope, an amphipathic compound, and a hydrophobic carrier, wherein the composition is for administration parenterally and the low dose volume is less than 100 μL, for inducing an antibody immune response to the B-cell epitope in a human subject.
Kit containing a parenteral low-dose composition
A kit for inducing an antibody immune response in a human subject comprising a low dose composition containing an antigen comprising a B-cell epitope, an amphipathic compound, and a hydrophobic carrier, wherein the composition is for administration parenterally and the low dose volume is less than 100 μL.
The claim set is anchored in a parenteral, low-dose-volume (<100 μL) antigen formulation that combines an amphipathic compound and a hydrophobic carrier to induce an antibody immune response to an antigen comprising a B-cell epitope, with corresponding coverage for both the composition and a kit containing the composition.
Stated Advantages
The oil-based low-volume dosing is reported to produce strong and detectable antibody titers and improved responder rates and endpoint titers compared with alum-based formulations.
Antibody responses are reported to persist to at least Day 84 or Day 236.
Acceptable safety is reported, including no serious adverse events.
Documented Applications
Human immunization/inducing an antibody immune response in a human subject against a B-cell epitope, exemplified with RSV SHeA and SHeB peptides and reported as clinical trial results for adults 50–64 years.
Nonclinical mouse evaluation of oil-based non-adjuvanted, oil-based adjuvanted, and aqueous formulations with ELISA-measured titers for RSV SHeA and SHeB.
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