Vaccines for HSV-2
Inventors
Dubensky, Jr., Thomas W. • Hosken, Nancy A. • Robbins, Scott H. • MOORE, MARGARET D.
Assignees
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Publication Number
US-10391164-B2
Publication Date
2019-08-27
Expiration Date
Abstract
Compositions of recombinant HSV-2 proteins and an agonist of the innate immune system, such as an adjuvant, are provided as a vaccine. Proteins include an envelope glycoprotein and a structural protein other than an envelope glycoprotein, e.g., a capsid or tegument protein. The vaccine is for use in either HSV-2 seropositive or seronegative subjects.
Core Innovation
The invention relates to HSV-2 vaccine compositions and methods of generating an immune response in a subject. The immunogenic pharmaceutical composition comprises an immunogenic fragment of an HSV-2 UL19 polypeptide and UL25, formulated with a monoacid lipid A (MALA) adjuvant.
The UL19 component is defined as an immunogenic fragment comprising the amino acid sequence set forth in SEQ ID NO: 12, with specified deletion constraints relative to SEQ ID NO: 4, or an immunogenic variant retaining at least 90% amino acid identity over the full length of the immunogenic fragment. The UL25 antigen comprises the amino acid sequence set forth in SEQ ID NO: 5 or an immunogenic fragment comprising at least 15 contiguous amino acids of SEQ ID NO: 5.
The adjuvant is monoacid lipid A (MALA), described as preferably a TLR4-acting monoacid lipid A such as GLA, including GLA in an oil-in-water/Squalene emulsion (GLA-SE) as well as aqueous forms. The document further describes claimed immunogens that can include additional HSV-2 proteins and immunogenic fragments in combination.
Claims Coverage
The document provides one independent method claim. The independent claim covers an immune-response generating administration comprising a defined UL19 immunogenic fragment, UL25, and a MALA adjuvant, with dependent claims adding administration routes, defining MALA as GLA and its formulation form, selecting an optional second adjuvant from a defined set, and adding additional HSV-2 antigens such as gD2 with defined sequence-fragment constraints.
UL19 immunogenic fragment with defined sequence and deletion constraints
The method includes an immunogenic fragment of an HSV-2 UL19 polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 12, wherein the immunogenic fragment lacks at least 75% of amino acids 1-450 of SEQ ID NO: 4 and lacks at least 75% of amino acids of 1055-1374 of SEQ ID NO: 4, or an immunogenic variant thereof that retains at least 90% amino acid identity over the full length of the immunogenic fragment.
UL25 antigen with defined sequence or contiguous fragment
The method includes UL25, wherein UL25 comprises the amino acid sequence set forth in SEQ ID NO: 5 or an immunogenic fragment thereof comprising at least 15 contiguous amino acids of SEQ ID NO: 5.
Monoacid lipid A (MALA) adjuvant
The immunogenic pharmaceutical composition further comprises a monoacid lipid A (MALA) adjuvant.
Administration routes for generating an immune response
The method further comprises administering the composition by intradermal, mucosal, intramuscular, subcutaneous, sublingual, rectal, or vaginal administration.
MALA is Glucopyranosyl Lipid Adjuvant (GLA)
The monoacid lipid A (MALA) adjuvant is Glucopyranosyl Lipid Adjuvant (GLA).
GLA formulation as oil-in-water emulsion or aqueous form
The GLA is provided either as an oil-in-water emulsion or in an aqueous form.
Optional second adjuvant selected from defined classes
The method further specifies that a second adjuvant is chosen from TLR7 agonist, TLR9 agonist, alum, an emulsion, a saponin, a cytokine, an unmethylated CpG dinucleotide, or a modified saponin.
Addition of gD2 antigen fragments with defined contiguous length
The method includes using HSV-2 protein gD2 that contains an amino acid sequence of SEQ ID NO: 2 or 3, or an immunogenic fragment comprising at least 15 contiguous amino acids of SEQ ID NO: 2 or 3.
Overall, the claim set is directed to generating an immune response by administering a composition containing a UL19 immunogenic fragment with specified sequence and deletion constraints, UL25 defined by SEQ ID NO: 5 or contiguous fragments, and a monoacid lipid A (MALA) adjuvant, with dependent refinements for administration routes, GLA identity and form, optional second adjuvant classes, and optional addition of gD2 defined by SEQ ID NO: 2 or 3.
Stated Advantages
Documented Applications
Prophylaxis and therapy against HSV-2 in seropositive and seronegative subjects are described, including use of the composition for generating an immune response in a subject.
A contemplated human Phase 1 safety/immunogenicity study is described.
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