Thermal inactivation of rotavirus
Inventors
Jiang, Baoming • Glass, Roger I. • Saluzzo, Jean-Francois
Assignees
US Department of Health and Human Services
Publication Number
US-10556001-B2
Publication Date
2020-02-11
Expiration Date
2028-09-04
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Abstract
Methods of thermally inactivating a rotavirus are provided according to the present invention which include exposing the rotavirus to a temperature in the range of about 50° C.-80° C., inclusive, for an incubation time sufficient to render the rotavirus incapable of replication or infection. The thermally inactivated rotavirus is antigenic and retains a substantially intact rotavirus particle structure. Vaccine compositions and methods of vaccinating a subject against rotavirus are provided which include generation and use of thermally inactivated rotavirus.
Core Innovation
The invention provides methods of thermally inactivating rotavirus by exposing the virus to temperatures ranging from about 50° C. to 80° C. for sufficient incubation times to render the rotavirus incapable of replication or infection. The thermally inactivated rotavirus remains antigenic and retains a substantially intact rotavirus particle structure, including triple-layered and double-layered particles. These methods enable the production of vaccine compositions that include thermally inactivated rotavirus capable of eliciting an immune response when administered to a subject.
Rotavirus causes severe diarrhea in children worldwide and results in a high mortality rate, with approximately 611,000 deaths per year. The virus is highly contagious and affects children across all socioeconomic and geographic groups. Although live oral vaccines exist, there are ongoing safety and efficacy concerns that justify development of an alternative approach. The background identifies a problem in finding effective methods to inactivate rotavirus while maintaining antigenicity and particle structure for vaccine use, particularly preserving the substantially intact double-layer and triple-layer rotavirus particles after inactivation.
The invention addresses the need for inactivated rotavirus vaccines by providing a thermal inactivation method that maintains the viral particle's integrity and antigenicity. The process includes suspending isolated rotavirus particles in an aqueous buffer with specific osmolality, divalent cation salts, and sugars or sugar alcohols, followed by heating within specified temperature and time ranges. The vaccines formed from these thermally inactivated rotaviruses can be administered parenterally to humans or animals and may include adjuvants to enhance immunogenicity. The thermally inactivated rotavirus stimulates an immune response characterized by production of neutralizing antibodies, reducing clinical signs and viral shedding.
Claims Coverage
The patent includes one independent claim that encompasses multiple inventive features related to the thermal inactivation method, vaccine composition, and immunization method for inducing an immune response to rotavirus.
Method of producing thermally inactivated rotavirus antigen
A process comprising suspending isolated rotavirus particles in an aqueous buffer having an osmolality of about 200-500 mOsm, containing a salt of a divalent cation (1-15 mM) and sugar and/or sugar alcohol (1-20% w/v), followed by exposing the preparation to a temperature between about 50° C. and 73° C. for 30 minutes to 24 hours, sufficient to render the virus incapable of replication or infection while maintaining antigenicity and substantially intact particle structure (triple-layer, double-layer, or a combination).
Vaccine composition including thermally inactivated rotavirus and adjuvant
A vaccine composition comprising antigenic thermally inactivated rotavirus with substantially intact particle structure, an adjuvant (such as AlOH, AlPO4, aluminum oxide, Freund's adjuvant, iron oxide, saponin, DEAE-dextran, mineral oil, or bacterial lipopolysaccharide), and a sterile pharmaceutically acceptable carrier formulated for administration.
Method of inducing an immune response by administering vaccine
Administering to a subject, including humans, a therapeutically effective amount of the vaccine composition by any suitable route, especially parenteral, with at least two doses to induce neutralizing antibodies and protective immunity against rotavirus infection, reducing viral shedding and symptoms.
The claims define a comprehensive approach covering the preparation of thermally inactivated rotavirus retaining structural and antigenic integrity, corresponding vaccine formulations with adjuvants and carriers, and vaccination methods involving parenteral administration inducing protective immune responses against rotavirus infections.
Stated Advantages
The thermally inactivated rotavirus retains antigenicity and substantially intact triple-layered or double-layered particle structures, preserving viral proteins important for immunogenicity.
The methods produce vaccines capable of eliciting robust total and neutralizing antibody responses, including in animal models.
Inclusion of adjuvants like aluminum hydroxide enhances immunogenicity, allowing effective vaccination with low doses of antigen.
Vaccination with the thermally inactivated rotavirus reduces virus shedding, duration of shedding, and symptoms upon rotavirus challenge in animal models, indicating protective efficacy.
Documented Applications
Vaccination of humans and various animals including cows, horses, sheep, goats, pigs, dogs, cats, birds, poultry, and rodents to prevent rotavirus-mediated disease.
Development of parenteral inactivated rotavirus vaccine formulations for inducing protective immunity against rotavirus infections.
Use of thermally inactivated rotavirus preparations in vaccine compositions with adjuvants for immunization protocols involving multiple doses.
Use of the vaccine compositions to reduce viral shedding, number of shedding days, and symptoms in subjects exposed to rotavirus.
Interested in licensing this patent?