Immunogens and methods for discovery and screening thereof

Inventors

Malley, RichardLu, YingjieMoffitt, Kristin L.

Assignees

Boston Childrens Hospital

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Publication Number

US-12370246-B2

Patent

Publication Date

2025-07-29

Expiration Date


Abstract

The present application is generally directed to methods for identifying immunogens from organisms and pathogens, and in particular for identifying immunogens which when administered as vaccines elicit a cellular and/or humoral immune response. The present application is also directed to pneumococcal T-cell immunogens, and vaccine compositions comprising one or a combination of pneumococcal immunogens and methods for treating or preventing pneumococcal infections using the vaccines thereof. The present invention also encompasses use of the pneumococcal immunogens for diagnostic purposes to identify a subject with a pneumococcal infection.

Core Innovation

The patent describes antigen discovery and vaccine candidate identification for Streptococcus pneumoniae by preserving soluble protective antigens through solvent-killing. The approach emphasizes solvent-killing of whole cell pneumococcus, followed by liquid-phase harvesting and fractionation to obtain antigen fractions for downstream immunological evaluation.

The disclosed workflow includes immunostimulation screening focused on IL-17A/Th17 responses. Antigen candidates are identified through immune readouts, including WCC and IL-17A splenocyte screening, and correlation of IL-17A whole blood responses with colonization protection in a mouse colonization model.

Using this process, the patent reports pneumococcal T-cell immunogens SP2070 (SEQ ID NO:10/11), SP1534 (SEQ ID NO:28/29), SP0862 (SEQ ID NO:8/9), and SP0435 (SEQ ID NO:44). The described candidates are said to elicit systemic IL-17A and reduce or protect against intranasal colonization when administered mucosally with cholera toxin adjuvant, relative to a negative control (SP2092).

The disclosure further states that the solvent-based antigen discovery method can be applied to other pathogens and immune endpoints, and it provides representative antigen panels (Table 1/2). It also includes multivalent vaccine compositions and mentions adjuvant options in the context of these immunogens.

Claims Coverage

The independent claim defines a method for inducing an IL17 immune response in a subject by administering an immunogenic composition that contains specified antigenic polypeptides and an adjuvant at suitable doses. It includes three main inventive elements: the defined antigenic polypeptides (specific SEQ ID NOs), the presence of an adjuvant, and dosing such that IL17 immune response is elicited.

Specific antigenic polypeptide set for IL17 induction

Administering to the subject an immunogenic composition comprising (i) an antigenic polypeptide comprising the amino acid sequence of SEQ ID NO:44 and (ii) an antigenic polypeptide comprising the amino acid sequence of SEQ ID NO:28 or SEQ ID NO:29, or an antigenic polypeptide comprising the amino acid sequence of SEQ ID NO:10 or SEQ ID NO:11.

Immunogenic composition includes an adjuvant

Administering the immunogenic composition further comprising an adjuvant.

Suitable doses elicit an IL17 immune response

Using suitable doses of the antigenic polypeptides such that upon administration the immunogenic composition elicits an IL17 immune response to the antigenic polypeptides in the subject.

Overall, the claim coverage centers on inducing an IL17 immune response using a defined immunogenic composition that combines SEQ ID NO:44 with one of the additional specified antigenic polypeptides (SEQ ID NO:28/29 or SEQ ID NO:10/11) together with an adjuvant at suitable doses.

Stated Advantages

Elicits systemic IL-17A.

Reduces or protects against intranasal colonization when administered mucosally with cholera toxin adjuvant.

Solvent-based antigen discovery method can be applied to other pathogens and immune endpoints.

Documented Applications

Inducing IL17 immune responses in a subject using an immunogenic composition comprising pneumococcal T-cell immunogens and an adjuvant.

Mucosally administering pneumococcal immunogens with cholera toxin adjuvant to reduce/protect against intranasal colonization in mice.

Applying the solvent-based antigen discovery method to other pathogens and other immune endpoints.

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