Immunogenic complex for vaccination and method for the production thereof
Inventors
SUBIZA GARRIDO LESTACHE JOSE LUIS, null • SUBIZA GARRIDO-LESTACHE, José Luis • CANADA VICINAY JAVIER, null • CAÑADA VICINAY, Javier • SORIA CASTRO, Irene • FERNÁNDEZ-CALDAS RODRÍGUEZ, Enrique • MANZANO PEREZ ANA, null • MANZANO PÉREZ, Ana • CASES ORTEGA, Bárbara • JIMENEZ BARBERO JESÚS, null • JIMÉNEZ BARBERO, JESÚS • CASANOVAS VERGES MIGUEL, null • CASANOVAS VERGÉS, Miguel
Assignees
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Publication Number
US-9901633-B2
Publication Date
2018-02-27
Expiration Date
Abstract
The present invention is related to an immunogenic complex comprising a polymerized antigen, mannan and a dialdehyde, the composition comprising it and the use thereof as an immune response stimulator and vaccine, useful in the treatment of infectious diseases, neoplasms and allergies. Likewise, the invention relates to the method for obtaining said immunogenic complex, based on the antigen and mannan simultaneous polymerization and conjugation by using a dialdehyde.
Core Innovation
The invention provides an immunogenic complex comprising a polymerized antigen, mannan comprising a peptide residue comprising amino groups, and a reacted dialdehyde. The polymerized antigen is bound to the amino groups of the mannan by the reacted dialdehyde, linking the antigen polymerization component to mannan through dialdehyde-mediated reactions.
The disclosure describes using a dialdehyde that enables simultaneous polymerization of the protein antigen or allergen and covalent or physical conjugation to mannan, yielding polymerized antigen bound to mannan via dialdehyde-mediated reactions. Dialdehydes described include glutaraldehyde and other dialdehyde species such as glyoxal, malonaldehyde, succinaldehyde, and adipaldehyde, with mannan providing amino groups through peptide residues.
The platform is used in an immunogenic and allergy-related context, where polymerized antigen bound to mannan is characterized by an antigen:mannan ratio as described in the disclosure. The approach is stated to improve dendritic cell uptake and function, while maintaining or enhancing T-cell responses and in vivo immunogenicity, including an altered cytokine and antibody profile consistent with antiallergic polarization.
Claims Coverage
The independent claim is directed to the structure of an immunogenic complex with a dialdehyde-mediated binding relationship between a polymerized antigen and mannan containing amino groups. Additional dependent claims further specify features such as the source and composition of mannan, the location of amino groups, the selection of dialdehydes, and quantitative formulation parameters including antigen:mannan ratio ranges.
Dialdehyde-mediated binding of polymerized antigen to mannan amino groups
An immunogenic complex comprising a polymerized antigen, mannan comprising a peptide residue comprising amino groups, and a reacted dialdehyde, wherein the polymerized antigen is bound to the amino groups of the mannan by the reacted dialdehyde.
Selected dialdehyde for reacted dialdehyde linkage
The reacted dialdehyde is selected from glutaraldehyde, glyoxal, malonaldehyde, succinaldehyde, or adipaldehyde.
Antigen to mannan ratio range for forming the complex
The complex is formed with an antigen:mannan ratio ranging between 1:10 and 1:0.15.
Lysine amino groups as the mannan amino group location
The amino groups are located on lysine amino acid.
Yeast-derived mannan source selection
Mannan is derived from yeast selected from Saccharomyces ssp., Pichia ssp., or Candida ssp.
Overall claim coverage centers on an immunogenic complex where a dialdehyde reaction enables binding of a polymerized antigen to mannan amino groups. Dependent claim refinements narrow the dialdehyde set, specify lysine-associated amino groups and yeast-derived mannan sources, and constrain antigen:mannan ratio ranges.
Stated Advantages
Reduced allergenicity, described as comparable loss of IgE reactivity and basophil activation, with low prick-test responses.
Improved dendritic cell uptake and function, described as higher IL-10/IL-6 and maturation markers comparable to non-mannosylated polymers.
Enhanced T-cell responses and in vivo immunogenicity, described as greater IFN-γ/IL-10-producing cells, higher T-cell proliferation, and altered cytokine/IgG2a/IgE ratios toward antiallergic polarization.
Documented Applications
Allergy/immunotherapy applications are described, including treatment/response assessment in relation to allergens and measurements such as IgE reactivity, basophil activation, and prick test responses.
Immunogenicity measurement in vivo is described in relation to T-cell responses and altered cytokine/antibody profiles for antiallergic polarization.
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