Poly(diaminosulfide) particle-based vaccine
Inventors
Salem, Aliasger K. • Wafa, Emad I. • Geary, Sean M. • Bowden, Ned B. • Wilson-Welder, Jennifer H. • Alt, David P.
Assignees
University of Iowa Research Foundation UIRF • US Department of Agriculture USDA
Publication Number
US-11904006-B2
Publication Date
2024-02-20
Expiration Date
2040-12-11
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Abstract
A composition comprising particles formed of poly(diaminosulfide) and one or more leptospiral antigens, and methods of making and using the composition, are provided.
Core Innovation
The invention provides a composition comprising particles formed of poly(diaminosulfide) and one or more leptospiral antigens, as well as methods for making and using this composition. The particles may be in the form of microparticles or nanoparticles with specified size ranges. The composition can include leptospiral lysates, isolated lipoproteins, or nucleic acid encoding leptospiral proteins. The composition is useful as a vaccine that may further comprise a pharmaceutically acceptable carrier and optionally an adjuvant.
The background section highlights leptospirosis as a widespread zoonotic disease caused by Leptospira bacteria, which affects both animals and humans. Current vaccines, mainly bacterins of single Leptospira serovars, have limitations such as short duration of protection, serovar-specific immunity, and inability to prevent renal colonization and shedding. There are safety concerns, especially for human use, due to adverse vaccination reactions from bacterin vaccines containing whole bacterial cellular components. Therefore, there is an unmet need for a vaccine platform that generates durable and broad immunity against leptospirosis with a suitable safety profile.
The summary describes the development of a first-in-class microparticle-based Leptospira vaccine using poly(diaminosulfide) polymer to encapsulate Leptospira borgpetersenii serovar Hardjo strain HB15B203 antigen (L203). The particles provide controlled sustained antigen release with zero-order kinetics and maintain antigen integrity. The vaccine formulation was tested in cattle, demonstrating enhanced humoral and cellular immune responses including increased L203-specific T and B cells, effector-memory T cell populations, cytokine production, and higher antibody titers compared to conventional aluminum hydroxide-adjuvanted vaccines. This platform offers thermal stability, potential multivalency, and represents a promising prophylactic vaccine against leptospiral infection in cattle.
Claims Coverage
The patent includes two independent claims covering a composition of poly(diaminosulfide) particles with leptospiral antigens and methods of immunization or prevention of infection using the composition. Below are the main inventive features derived from the independent claims.
Composition of poly(diaminosulfide) particles with leptospiral antigens
A composition comprising nanoparticles or microparticles comprising poly(diaminosulfide) and one or more leptospiral antigens, with particles having defined size ranges for micro- and nanoparticles, antigen loading in specific amounts, and poly(diaminosulfide) polymers having molecular weights from about 2,000 to 100,000 g/mol. The leptospiral antigens can be lysates of inactivated Leptospira and may originate from multiple serovars.
Vaccine comprising the composition
A vaccine formulation comprising the poly(diaminosulfide)-based particle composition, optionally including a pharmaceutically acceptable carrier and optionally including or lacking an adjuvant, with specified ranges of leptospires or protein/lysate quantities in the vaccine.
Method for immunizing or preventing infection in a mammal
A method for immunizing a mammal or preventing/inhibiting Leptospira infection by administering an effective amount of the poly(diaminosulfide)-leptospiral antigen particle composition to mammals including bovine, human, swine, caprine, equine, canine, feline, ovine, or lagomorph species via injection, systemic, oral, subcutaneous, or intravenous routes, including administration of two or more doses.
The independent claims collectively cover the composition of poly(diaminosulfide) particles carrying leptospiral antigens, vaccines formulated with these particles, and methods for immunization or infection prevention in mammals using the composition administered by various routes and dosing schemes.
Stated Advantages
The vaccine delivery vehicle is thermally stable up to approximately 90° C., an advantage for use in tropical and resource-poor regions without refrigeration.
The composition provides a sustained zero-order release of antigen, ensuring extended availability for uptake by antigen-presenting cells, which promotes durable immune responses potentially with fewer doses.
Encapsulation preserves antigen functionality and immunoreactivity, including key proteins and lipopolysaccharide (LPS) from Leptospira.
The vaccine formulation elicits enhanced Leptospira-specific cellular and humoral immune responses in cattle, including increased T cell subsets, B cells, cytokine production, and antibody titers, compared to conventional adjuvant vaccines.
The platform is biocompatible, biodegradable, and well tolerated with no observed local adverse reactions in cattle during testing.
Documented Applications
Use as a prophylactic vaccine to immunize mammals including cattle, humans, swine, caprine, equine, canine, feline, ovine, or lagomorphs against leptospiral infection.
Use for preventing or inhibiting Leptospira infection in mammals by administering the poly(diaminosulfide)-based leptospiral antigen particle composition.
Interested in licensing this patent?