Vaccine against streptococcal infections based on recombinant proteins
Inventors
Guss, Bengt • Flock, Jan-Ingmar • Frykberg, Lars • Flock, Margareta
Assignees
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Publication Number
US-9795664-B2
Publication Date
2017-10-24
Expiration Date
Abstract
An antigenic composition comprises several antigenic components derived from antigens of Streptococcus equi subsp. equi or subsp. zooepidemicus, wherein at least one component is a fusion protein or polypeptide compromising two or more such antigens or fragments thereof. The antigenic composition may be used for immunization of mammals against S. equi subsp. equi and/or subsp. zooepidemicus. A vaccine composition comprising the antigenic composition as immunizing component is also disclosed.
Core Innovation
The invention provides methods for producing antiserum and for prophylactic or therapeutic treatment of Streptococcus equi infection by using antigenic compositions composed of multiple antigenic components derived from Streptococcus equi subsp. equi and/or Streptococcus equi subsp. zooepidemicus. The antigenic components include fusion polypeptides and/or polypeptides in which each included protein segment comprises at least one antigenic epitope.
A defining feature is the inclusion of a first fusion polypeptide comprising at least part of a protein designated EAG and at least a part of a protein designated CNE. Additional antigenic components include at least one additional polypeptide selected from Eq5/Eq8, IdeE/Eq5, IdeE, IdeE2, Eq27, Eq54, and Scl family proteins, and the antigenic composition further comprises at least part of EndoSe or EndoSz in the antiserum-producing embodiment.
For treatment, the antigenic composition is administered as a vaccine composition that includes a pharmaceutically acceptable carrier and is framed as an immunologically effective amount against Streptococcus equi infection. In the described studies, vaccine formulations are compared, and outcomes include reduced clinical symptoms/pyrexia, improved protection versus placebo, and antigen-specific antibody responses measured by ELISA.
Claims Coverage
The provided claim set includes four independent claims directed to production of antiserum and prophylactic or therapeutic treatment. Across these claims, the inventive core is the use of a Streptococcus equi subsp. equi and/or subsp. zooepidemicus-derived, epitope-containing multi-component antigenic composition built around a specified EAG/CNE fusion and selected additional fusion polypeptides/polypeptides, with EndoSe or EndoSz included in the antiserum-producing embodiment and a pharmaceutically acceptable carrier in the vaccine-directed embodiment.
Antiserum production with multi-component Streptococcus equi epitope-containing antigenic composition
A method for the production of an antiserum comprising administering an antigenic composition to a non-human mammal host to produce antibodies and recovering antiserum, wherein the antigenic composition comprises a plurality of antigenic components derived from Streptococcus equi subsp. equi or subsp. zooepidemicus, including a first fusion polypeptide with EAG and CNE defined by specified amino acid sequences starting from amino acid 12, at least one additional polypeptide selected from Eq5/Eq8, IdeE/Eq5, IdeE, IdeE2, Eq27, Eq54, and Scl family proteins, each comprising at least one antigenic epitope, and further comprising at least part of EndoSe or EndoSz.
Prophylactic or therapeutic treatment via vaccine with EAG/CNE fusion plus optional additional polypeptides
A method of prophylactic or therapeutic treatment of Streptococcus equi infection in a mammal comprising administering to the mammal an immunologically effective amount of a vaccine composition, wherein the vaccine comprises an antigenic composition derived from Streptococcus equi subsp. equi or subsp. zooepidemicus including a first fusion polypeptide with EAG and CNE defined by amino acid sequences as shown in SEQ ID NO: 24, SEQ ID NO: 28, or SEQ ID NO: 34 starting from amino acid 12, and at least one additional polypeptide selected from Eq5/Eq8, IdeE/Eq5, EndoSe/EndoSz, IdeE, IdeE2, Eq27, Eq54, and Scl family proteins, wherein each included at least part comprises at least one antigenic epitope, and the composition includes a pharmaceutically acceptable carrier.
Prophylactic or therapeutic treatment via vaccine with EAG/CNE fusion and Eq5/Eq8 fusion defined by SEQ ID NO: 22
A method of prophylactic or therapeutic treatment of Streptococcus equi infection in a mammal comprising administering an immunologically effective amount of a vaccine composition, wherein the vaccine comprises an antigenic composition derived from Streptococcus equi subsp. equi or subsp. zooepidemicus including a first fusion polypeptide with EAG and CNE and a second fusion polypeptide comprising Eq5 and Eq8 having the amino acid sequence as shown in SEQ ID NO: 22 starting from amino acid 12, and optionally at least one additional polypeptide selected from IdeE/Eq5, EndoSe/EndoSz, IdeE, IdeE2, Eq27, Eq54, and Scl family proteins, wherein each at least part comprises at least one antigenic epitope, and the composition includes a pharmaceutically acceptable carrier.
Prophylactic or therapeutic treatment via vaccine with EAG/CNE fusion and IdeE/Eq5 fusion defined by SEQ ID NO: 30
A method of prophylactic or therapeutic treatment of Streptococcus equi infection in a mammal comprising administering an immunologically effective amount of a vaccine composition, wherein the vaccine comprises an antigenic composition derived from Streptococcus equi subsp. equi or subsp. zooepidemicus including a first fusion polypeptide with EAG and CNE and a third fusion polypeptide comprising IdeE and Eq5 having the amino acid sequence as shown in SEQ ID NO: 30 starting from amino acid 12, and optionally at least one additional polypeptide selected from Eq5/Eq8, EndoSe/EndoSz, IdeE, IdeE2, Eq27, Eq54, and Scl family proteins, wherein each at least part comprises at least one antigenic epitope, and the composition includes a pharmaceutically acceptable carrier.
Across the independent claims, the inventive coverage centers on administering or using epitope-containing, Streptococcus equi-derived antigenic compositions built around an EAG/CNE fusion polypeptide plus additional specified fusion polypeptides/polypeptides, and, in the antiserum-producing embodiment, further comprising EndoSe or EndoSz. The vaccine-directed independent claims frame these multi-component antigenic compositions in an immunologically effective prophylactic or therapeutic method using a pharmaceutically acceptable carrier.
Stated Advantages
Reduced clinical symptoms/pyrexia and improved protection versus placebo for described Strangvacc variants.
Antigen-specific antibody responses are generated, with IgG titers measured by ELISA.
Documented Applications
Production of antiserum by administering the antigenic composition to a non-human mammal host and recovering antiserum containing antibodies produced in the host.
Prophylactic or therapeutic treatment of Streptococcus equi infection in a mammal by administering an immunologically effective amount of the vaccine composition formulated with a pharmaceutically acceptable carrier.
Protection of horses from Streptococcus equi infection using the vaccine composition.
Inducing an immune response in a horse characterized by IgG and/or IgA and/or IgM antibodies in serum and/or nasopharyngeal mucus.
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