Vaccine against S. suis infection

Inventors

Guss, Bengt • Frykberg, Lars • Flock, Margareta • Flock, Jan-Ingmar • ZACHRISSON, Karl Olov

Assignees

Intervacc AB

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Publication Number

US-11814415-B2

Patent

Publication Date

2023-11-14

Expiration Date


Abstract

The present disclosure relates to immunogenic polypeptides, immunogenic compositions and vaccine compositions and use thereof for immunization of mammals susceptible to Streptococcus suis infection. The disclosure also relates to methods for preparing, formulating and administrating such compositions.

Core Innovation

The invention relates to a vaccine against Streptococcus suis infection and to a method and immunogenic composition for immunizing a mammalian subject against a Streptococcus suis infection by administering an immunologically effective amount of a fusion protein. The fusion protein comprises a first immunogenic polypeptide unit and a second immunogenic polypeptide unit, where the immunogenic polypeptide units are immunogenic polypeptide fragments selected from specified SEQ ID fragments and variants with sequence identity and fragment length limits.

The disclosed immunogenic polypeptides include fragments selected from surface-expressed antigens including IdeE/M2 and nucleotidases SP2, SP4, and SP7, and fusion constructs such as SP2M2 and SP74C. The fragments used to form the units are taken from different native proteins and assembled into fusion constructs for immunization, with an optional third immunogenic polypeptide unit derived from a different native protein.

The disclosure also describes immunogenic compositions and vaccine compositions containing the immunogenic polypeptides and/or fusion proteins. Optional silica-binding silica tag (SL2/LSL) constructs are associated with immunogenic fusion polypeptides, and optional adjuvant agents include silica and Abisco/Matrix M, Matrix C, or Matrix Q.

Claims Coverage

The independent claims cover immunizing a mammalian subject against Streptococcus suis infection using immunogenic compositions containing fusion proteins or immunogenic polypeptides. The inventive features center on specified SEQ ID selection, at least 80% identity, and fragment length restrictions, with dependent claims further adding an optional third immunogenic polypeptide unit and specific fusion protein sequence restrictions.

Fusion protein with first and second immunogenic polypeptide units for immunization

A method for immunizing a mammalian subject against a Streptococcus suis infection by administering an immunologically effective amount of an immunogenic composition comprising a fusion protein comprising a first immunogenic polypeptide unit and a second immunogenic polypeptide unit, wherein the first and second immunogenic polypeptide units are immunogenic polypeptide fragments selected from specified SEQ ID fragments and variants with at least 80% identity and length limits.

Immunogenic polypeptide fragment defined by SEQ ID selection with identity and length limits

A method for immunizing a mammalian subject against a Streptococcus suis infection by administering an immunologically effective amount of an immunogenic polypeptide fragment selected from SEQ ID NO:8, SEQ ID NO:10, and SEQ ID NO:12, or an amino acid sequence with at least 80% identity to an amino acid sequence defined in i), wherein the fragment is less than 500 amino acids long.

Vaccine composition with immunogenic polypeptide units defined by SEQ ID identity and less-than-500-aa length

A method for immunizing a mammalian subject against a Streptococcus suis infection by administering an immunologically effective amount of a vaccine composition comprising an immunogenic polypeptide unit with at least 80% identity with SEQ ID NO:8, SEQ ID NO:10, or SEQ ID NO:12, wherein the immunogenic polypeptide units are less than 500 amino acids long.

Optional third immunogenic polypeptide unit from a different native protein

An optional third immunogenic polypeptide unit is included in the immunogenic composition, derived from a different native protein than the first and second immunogenic polypeptide units.

Fusion protein sequence restrictions to specified SEQ ID NO options

The fusion protein amino acid sequence is restricted to SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, and SEQ ID NO:110, or sequences with at least 80% identity to one of those sequences.

Overall, the claim coverage centers on immunizing a mammalian subject against Streptococcus suis infection using an immunogenic composition that contains a fusion protein defined by two immunogenic polypeptide units selected via specified identity and length constraints, with dependent claims further restricting fragment sequence options, adding an optional third immunogenic unit, and restricting the fusion protein to defined SEQ ID NO sequences or identity variants.

Stated Advantages

Reduced post-challenge clinical scores and mortality in piglets vaccinated with the described fusion antigen.

Boosted IgG responses after a second dose in piglets immunized with fusion antigens.

Low DNA background in purified antigens/fusions prepared by the described silica and Q-sepharose purification approaches.

Stability of purified antigens/fusions is reported following stability testing.

Documented Applications

Immunization of mice with silica-bead formulated antigens to generate ELISA-detectable antibody responses.

Immunization of piglets with fusion antigens, including SP2M2-S and SP74C-S, to elicit boosted IgG after a second dose.

Piglet challenge study after vaccination with SP274C-S, including reporting clinical scores, mortality, and bacteriological recovery differences between vaccine and control groups.

Purification of SL2-tagged polypeptides and fusion polypeptides using silica-based purification approaches, with reported comparison to a His-tagged control.

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