Labyrinthin-based peptides for cancer immunotherapies and uses thereof
An antigenic composition containing labyrinthin-derived peptides with T-cell and B-cell epitopes addresses the challenge of treating heterogeneous cancers by inducing a targeted immune response against labyrinthin-expressing cancer cells, offering an improved therapeutic option.
Patent Information
- Application Number
- JP2025003947
- Authority / Receiving Office
- JP · JP
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2018-12-13
- Filing Date
- 2025-01-10
- Publication Date
- 2025-05-09
AI Technical Summary
Current cancer treatments based on histological type or organ of origin are insufficient for guiding effective therapies due to cancer heterogeneity, and there is a need for more targeted approaches, such as those utilizing biomarkers, to develop effective treatments for specific cancer subtypes like those expressing labyrinthin.
Development of an antigenic composition comprising one or more labyrinthin-derived peptides, which include T-cell and B-cell epitopes, designed to trigger adaptive immune responses and effectively target and destroy cancer cells expressing labyrinthin.
The antigenic composition induces a robust immune response that specifically targets and destroys labyrinthin-expressing cancer cells, providing an improved treatment approach for these cancer subtypes.
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Figure 2025072379000001_ABST
Abstract
Description
[Technical field]
[0001] [CROSS REFERENCE TO RELATED APPLICATIONS] This application claims priority to U.S. Provisional Patent Application No. 62 / 779,377, filed December 13, 2018, the disclosure of which is incorporated herein by reference in its entirety.
[0002] [Submit sequence listing as an ASCII text file] The contents of the following submitted document, an ASCII text file, are hereby incorporated by reference in its entirety: Sequence Listing in Computer Readable Form (CRF) (Filename: 185722000140SEQLIST.TXT, Date Recorded: December 10, 2019, Size: 8KB).
[0003] [Technical field] In some aspects, the present application relates to antigenic compositions comprising one or more labyrinthin-derived peptides. In other aspects, the present application relates to antigenic compositions comprising one or more labyrinthin-derived peptides, wherein each peptide comprises a T cell epitope and / or a B cell epitope. In other aspects, the present application relates to antibodies produced by vaccinating a subject with a composition disclosed herein. [Background technology]
[0004] Historically, cancers have been characterized largely based on the tissue type or organ from which they originate, e.g., lung, breast, and colon cancers. Many cancer treatments are also based on tissue- or organ-based classification of cancers. It is well recognized that such tissue- or organ-based classification of cancers may not provide sufficient guidance for the selection of effective treatments. This is due, in part, to the knowledge that cancers originating from a single tissue type or organ may be highly heterogeneous, and such differences may require individualized cancer treatment approaches. For example, defining cancers by biomarkers, as opposed to tissue type or organ of origin, may allow for improved cancer treatment, e.g., triple-negative breast cancers that lack expression of estrogen receptors, progesterone receptors, and HER2 / neu are not responsive to traditional hormone-based therapies targeting any one or more of the identified receptors and require alternative therapies. After identifying cancer subtypes based on biomarkers, significant research is needed to develop new drugs for the effective treatment of such cancer subtypes.
[0005] One such identified cancer subtype is labyrinthin-expressing cancer. Labyrinthin is a cell surface protein expressed on the extracellular surface of the cell membrane of some cancers, such as adenocarcinoma. The cell surface expression of labyrinthin is not cell cycle specific. Furthermore, labyrinthin is not found in the serum of normal or tumor-bearing patients and is not excreted into the medium by labyrinthin-positive cell lines. Therefore, labyrinthin is a useful marker for defining cancer subtypes, i.e., labyrinthin-expressing cancers.
[0006] Cancer vaccines that target Labyrinthin-expressing cancers via antibody production of the adaptive immune system mediated exclusively by B cells have been disclosed, see U.S. Patent Nos. 6,166,176 and 7,635,759, which are incorporated herein by reference in their entireties.
[0007] All references cited herein, including patent applications and publications, are incorporated by reference in their entirety. Summary of the Invention
[0008] In one aspect, the present application provides an antigenic composition comprising one or more labyrinthin-derived peptides. In some embodiments, the present application provides an antigenic composition comprising one or more labyrinthin-derived peptides, wherein each labyrinthin-derived peptide comprises one or more T cell epitopes and B cell epitopes. In some embodiments, each of the one or more labyrinthin-derived peptides comprises a T cell epitope and a B cell epitope. In some embodiments, the one or more labyrinthin-derived peptides are 8 to 25 amino acids in length. In some embodiments, the one or more labyrinthin-derived peptides are substantially homologous to a portion of labyrinthin. In some embodiments, each of the one or more labyrinthin-derived peptides comprises a non-terminal proline residue.
[0009] In another aspect, the present application provides an antigenic composition comprising one or more labyrinthin-derived peptides selected from the group consisting of: (a) a first peptide comprising SEQ ID NO:25 or a variant thereof; (b) a second peptide comprising SEQ ID NO:26 or a variant thereof; (c) a third peptide comprising SEQ ID NO:27 or a variant thereof; and (d) a fourth peptide comprising SEQ ID NO:28 or a variant thereof, wherein the one or more labyrinthin-derived peptides are 12 to 25 amino acids in length, and each peptide comprises a T cell epitope and a B cell epitope. In some embodiments, the first peptide comprises SEQ ID NO:25. In some embodiments, the second peptide comprises SEQ ID NO:26. In some embodiments, the third peptide comprises SEQ ID NO:27. In some embodiments, the fourth peptide comprises SEQ ID NO:28.
[0010] In some embodiments, the one or more labyrinthin-derived peptides are 21 to 24 amino acids in length. In some embodiments, the one or more labyrinthin-derived peptides are 22 or 23 amino acids in length.
[0011] In some embodiments, one or more labyrinthin-derived peptides are substantially homologous to a portion of labyrinthin.
[0012] In some embodiments, the first peptide is SEQ ID NO:29, or a variant thereof having one or two amino acids substituted, deleted, inserted, and / or added to SEQ ID NO:29. In some embodiments, the first peptide is SEQ ID NO:29.
[0013] In some embodiments, the second peptide is SEQ ID NO:30, or a variant thereof having one or two amino acids substituted, deleted, inserted, and / or added to SEQ ID NO:30. In some embodiments, the second peptide is SEQ ID NO:30.
[0014] In some embodiments, the third peptide is SEQ ID NO:31, or a variant thereof having one or two amino acids substituted, deleted, inserted, and / or added to SEQ ID NO:31. In some embodiments, the third peptide is SEQ ID NO:31.
[0015] In some embodiments, the fourth peptide is SEQ ID NO:32, or a variant thereof having one or two amino acids substituted, deleted, inserted, and / or added to SEQ ID NO:32. In some embodiments, the fourth peptide is SEQ ID NO:32.
[0016] In some embodiments, at least one of the one or more Labyrinthin-derived peptides is conjugated to a linker.
[0017] In some embodiments, the antigenic composition comprises two or more labyrinthin-derived peptides. In some embodiments, the antigenic composition comprises three or more labyrinthin-derived peptides. In some embodiments, the antigenic composition comprises four labyrinthin-derived peptides.
[0018] In another aspect, the present application provides nucleic acid compositions comprising one or more nucleic acids encoding at least one of one or more Labyrinthin-derived peptides comprised in the antigenic compositions described herein.
[0019] In another aspect, the present application provides a vaccine composition comprising: (a) an effective amount of an antigenic composition described herein; and (b) a pharma- ceutically acceptable vehicle. In some embodiments, the pharma- ceutically acceptable vehicle is selected from the group consisting of an aqueous suspension, an oil suspension, an emulsion, a liposome, a virosome, and a nanoparticle. In some embodiments, the pharma- ceutical acceptable vehicle comprises an additive. In some embodiments, the pharma- ceutical acceptable vehicle comprises an adjuvant. In some embodiments, the adjuvant is an immune enhancing adjuvant.
[0020] In another aspect, the application provides a method for treating cancer in an individual in need thereof, comprising administering to the individual a vaccine composition described herein, in some embodiments, the method further comprises administering to the individual an immune checkpoint inhibitor.
[0021] In another aspect, the application provides a method of producing antibodies in a host animal, comprising administering to the host animal an antigenic composition described herein, a nucleic acid composition described herein, or a vaccine composition described herein, thereby producing antibodies. [Brief description of the drawings]
[0022] [Figure 1A] FIG. 1A shows the mass spectrum of the parent ion m / z of a candidate Labyrinthin-derived peptide. [Figure 1B] FIG. 1B shows the mass spectrum of the parent ion m / z of a candidate Labyrinthin-derived peptide. [Figure 1C] FIG. 1C shows the mass spectrum of the parent ion m / z of a candidate Labyrinthin-derived peptide. [Figure 1D]FIG. 1D shows the mass spectrum of the parent ion m / z of a candidate Labyrinthin-derived peptide.
[0023] [Diagram 2] FIG. 2 shows UPLC traces of four labyrinthin-derived peptides (SEQ ID NOs: 29-32) reconstituted in isolyte (pH 7.4) or water.
[0024] [Diagram 3] FIG. 3 shows a graph of tumor weight (mg) versus days following administration of peptide vaccine (LabVax3(22)-23) or saline control to mice implanted subcutaneously with MC38 mouse colon (adenocarcinoma) tumor cells. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0025] The present application provides, in some aspects, antigenic compositions comprising one or more labyrinthin-derived peptides. In some embodiments, the labyrinthin-derived peptide comprises a T cell epitope. In some embodiments, the labyrinthin-derived peptide comprises a B cell epitope. In some embodiments, the labyrinthin-derived peptide comprises a B cell and a T cell epitope. In some embodiments, the labyrinthin-derived peptide activates T cell and B cell adaptive immune responses. In some embodiments, the one or more labyrinthin-derived peptides are 8 to 25 amino acids in length, for example 12 to 25 amino acids in length.
[0026] The disclosure of the present application is based in part on the discovery that Labyrinthin-derived peptides can be designed to include B cell epitopes and / or T cell epitopes to trigger a B cell-mediated adaptive immune response and also induce a T cell-mediated adaptive immune response to more effectively destroy cancer cells. In some embodiments, the disclosure of the present application is based in part on the discovery that Labyrinthin-derived peptides can be designed to induce an immune response to effectively destroy cancer cells. Vaccines comprising such Labyrinthin-derived peptides, and combinations comprising one or more of such Labyrinthin-derived peptides, will allow for improved treatment of Labyrinthin-expressing cancers.
[0027] Designing labyrinthin-derived peptides containing B and T cell epitopes is challenging because the mechanisms of antigen recognition are significantly different between B and T cells. B cells target solvent-exposed antigens, including both linear and conformational antigens, via antigen receptors that include immunoglobulins. In contrast, T cells recognize antigens presented on the surface of antigen-presenting cells (APCs) via T cell receptors. Such antigens are processed by APCs and then presented on the surface of APCs, for example, by class I major histocompatibility complex (MHCI) or class II major histocompatibility complex (MHCII). See, e.g., Sanchez-Trincado, JL et al., J Immunol, 2017.
[0028] In vivo antigen recognition by B cells and T cells is highly unpredictable. Increasing the length of peptide antigens increases cross-reactivity with non-target antigens. Therefore, it is challenging to generate peptides that can activate B cell and T cell immune responses with high target specificity, can be synthesized, can be stably formulated in pharma- ceutically acceptable vehicles, are safe for in vivo use, and generate immunogenic responses that are sufficiently effective for cancer treatment. The present application discloses Labyrinthin-derived peptides that contain B cell and T cell epitopes and are suitable for use in cancer vaccines.
[0029] Thus, the present disclosure provides, in some aspects, an antigenic composition comprising one or more labyrinthin-derived peptides, wherein each labyrinthin-derived peptide comprises one or more T cell epitopes and B cell epitopes. In some embodiments, each of the one or more labyrinthin-derived peptides comprises a T cell epitope and a B cell epitope. In some embodiments, the one or more labyrinthin-derived peptides are 8 to 25 amino acids in length. In some embodiments, the one or more labyrinthin-derived peptides are substantially homologous to a portion of labyrinthin. In some embodiments, each of the one or more labyrinthin-derived peptides comprises a non-terminal proline residue.
[0030] In another aspect, the disclosure provides an antigenic composition comprising one or more labyrinthin-derived peptides selected from the group comprising: (a) a first peptide comprising SEQ ID NO:25 or a variant thereof; (b) a second peptide comprising SEQ ID NO:26 or a variant thereof; (c) a third peptide comprising SEQ ID NO:27 or a variant thereof; and (d) a fourth peptide comprising SEQ ID NO:28 or a variant thereof, wherein the one or more labyrinthin-derived peptides are 12 to 25 amino acids in length, and each peptide comprises a T cell epitope and a B cell epitope. In some embodiments, the one or more labyrinthin-derived peptides comprise two or more labyrinthin-derived peptides. In some embodiments, the one or more labyrinthin-derived peptides comprise three or more labyrinthin-derived peptides. In some embodiments, the one or more labyrinthin-derived peptides comprise four labyrinthin-derived peptides. Compositions comprising the antigenic compositions disclosed herein, including kits, pharmaceuticals, and compositions thereof (such as pharmaceutical compositions and unit dosages) are also provided.
[0031] In another aspect, the present disclosure provides a vaccine composition comprising: (a) an antigenic composition disclosed herein; and (b) a pharma- ceutically acceptable vehicle. Vaccine compositions comprising the antigenic compositions disclosed herein, including kits, pharmaceuticals, and compositions thereof (such as pharmaceutical compositions and unit dosages), are also provided.
[0032] In another aspect, the disclosure provides a method for treating cancer in an individual in need of treatment, comprising administering to the individual a vaccine composition described herein.
[0033] In another aspect, the disclosure provides a method of producing antibodies in a host animal comprising administering to the host animal any of the antigenic compositions, nucleic acids, or vaccine compositions described herein, thereby producing antibodies.
[0034] It will also be understood by those skilled in the art that modifications of the embodiments and details described herein may be made without departing from the scope of this disclosure. In addition, although various advantages, aspects, and objectives have been described with reference to various embodiments, the scope of this disclosure should not be limited by reference to such advantages, aspects, and objectives.
[0035] [Definition] The term "substantially homologous" as used herein refers to the sequence similarity of a sequence disclosed herein compared to a reference sequence, where the sequence has at least about 85% similarity (e.g., homology) with the reference or a portion thereof, such as at least about 86% similarity, 87% similarity, 88% similarity, 89% similarity, 90% similarity, 91% similarity, 92% similarity, 93% similarity, 94% similarity, 95% similarity, 96% similarity, 97% similarity, 98% similarity, 99% similarity, or 100% similarity. Methods for determining sequence similarity are known in the art, for example, as described in Pearson, WR, Curr Protoc Bioinformatics, 2013.
[0036] The term "treating" or "treatment" as used herein is an approach to obtain beneficial or desired results, including clinical results. For purposes of this application, beneficial or desired clinical results include, but are not limited to, one or more of the following: alleviating one or more symptoms attributable to the disease, reducing the extent of the disease, stabilizing the disease (e.g., preventing or slowing the progression of the disease), preventing or slowing the spread of the disease (e.g., metastasis), preventing or slowing the recurrence of the disease, slowing or slowing the progression of the disease, ameliorating the disease state, providing remission of the disease (e.g., partial or total disease), reducing the dosage of one or more other medications required to treat the disease, slowing the progression of the disease, improving quality of life, and / or prolonging survival. "Treating" or "treatment" also includes reducing the pathological consequences of cancer. The methods of the present application contemplate any one or more of these aspects of treatment.
[0037] As used herein, the term "combination therapy" or "combination treatment" means that a first agent is administered in conjunction with at least one other agent. "In conjunction" refers to the administration of one therapeutic modality, such as a vaccine composition, in addition to, but not necessarily at the same time, the administration of another therapeutic modality. Thus, "in conjunction" refers to the administration of one therapeutic modality before, during, or after the delivery of the other therapeutic modality to an individual.
[0038] The term "effective amount" as used herein refers to an amount of a compound or composition sufficient to treat a particular disorder, condition, or disease, such as ameliorating, alleviating, reducing, and / or delaying one or more symptoms of the disorder, condition, or disease. With respect to cancer, an effective amount includes, for example, an amount sufficient to shrink a tumor and / or reduce the rate of tumor growth (e.g., inhibit tumor growth), or prevent or delay other undesirable cell proliferation in cancer. In some embodiments, an effective amount is an amount sufficient to delay the onset of cancer. In some embodiments, an effective amount is an amount sufficient to prevent or delay recurrence. An effective amount may be administered in one or more administrations. In the case of cancer, an effective amount of an agent or composition will (i) reduce the number of cancerous cells; (ii) reduce tumor size; (iii) inhibit, retard, slow to some extent, and preferably stop, cancer cell invasion into peripheral organs; (iv) inhibit (e.g., slow to some extent, and preferably stop) tumor metastasis; (v) inhibit tumor growth; (vi) prevent or delay the onset and / or recurrence of tumors; and / or (vii) alleviate to some extent one or more symptoms associated with cancer.
[0039] As used herein, the term "simultaneous administration" or synonyms thereof means that a first and second therapeutic agent in a combination therapy are administered with a time separation of about 15 minutes or less, e.g., about 10 minutes, 5 minutes, or 1 minute or less. When the first and second therapeutic agents are administered simultaneously, the first and second therapeutic agents can be included in the same composition (e.g., a composition that includes both the first and second therapeutic agents) or in separate compositions (e.g., the first therapeutic agent is included in one composition and the second therapeutic agent is included in another composition).
[0040] As used herein, the term "sequential administration" or synonyms thereof means that the first and second therapeutic agents in a combination therapy are administered with a time separation of any of more than about 15 minutes, e.g., more than about 20 minutes, 30 minutes, 40 minutes, 50 minutes, or 60 minutes. The methods disclosed herein encompass scenarios in which either the first or second therapeutic agent may be administered first. The first and second therapeutic agents will generally be contained in separate compositions that may be included in the same or different packages or kits.
[0041] As used herein, the term "concurrent administration" or equivalents refers to the overlap of the administration of a first therapeutic agent and the administration of a second therapeutic agent in a combination therapy.
[0042] The term "individual" refers to a mammal, including, but not limited to, a human, bovine, equine, feline, canine, rodent, or primate.
[0043] As used herein, "delaying" the onset of cancer means to postpone, prevent, slow, retard, stabilize, and / or prolong the onset of the disease. This delay can be for a variety of lengths of time, depending on the history of the disease and / or the individual being treated. As will be apparent to one of skill in the art, a sufficient or significant delay can, in effect, encompass prevention, in that the individual does not develop the disease. A method that "delays" the onset of cancer is one that reduces the likelihood of disease onset in a given time frame and / or reduces the extent of disease in a given time frame, compared to not using the method. Such comparisons are typically based on clinical trials using a statistically significant number of subjects. The onset of cancer can be detected using standard methods, including, but not limited to, computed tomography (CAT scan), magnetic resonance imaging (MRI), abdominal ultrasound, coagulation tests, arteriography, or biopsy. Onset may also be initially undetectable and may refer to the progression of cancer, including emergence, recurrence, and onset.
[0044] As used herein, the terms "pharmacologically acceptable" or "pharmacologically compatible" mean a material that is not biologically or otherwise undesirable, e.g., the material may be incorporated into a pharmaceutical composition administered to a patient without producing any significant undesirable biological effects or interacting in a deleterious manner with any of the other components of the composition in which it is contained. Pharmaceutically acceptable carriers, excipients, or salts preferably have met the required standards of toxicological and manufacturing testing and / or are included in the Inactive Ingredients Guide prepared by the U.S. Food and Drug Administration.
[0045] The term "based on" or "basis" as used herein includes assessing, determining, obtaining, or measuring one or more characteristics of an individual or a cancer therein as described herein, and in some embodiments, selecting an individual suitable for receiving a treatment as described in the methods disclosed herein. For example, if the labyrinthin status of a cancer is used as a basis for selecting an individual for a treatment method herein, assessing (or assisting in the assessment), measuring, obtaining, or determining the labyrinthin status can be included in the treatment method described herein, for example, the labyrinthin status is measured before and / or during and / or after treatment, and the resulting value is used by a clinician in assessing any of the following: (a) the likelihood or likelihood that an individual is suitable to receive treatment initially; (b) the likelihood or likelihood that an individual is not suitable to receive treatment initially; (c) responsiveness to treatment; (d) the likelihood or likelihood that an individual is suitable to continue receiving treatment; (e) the likelihood or likelihood that an individual is not suitable to continue receiving treatment; (f) dosage adjustment; or (g) prediction of the likelihood of clinical benefit.
[0046] The basis disclosed herein for use with the methods of the present application, e.g., labyrinthin status, may in some aspects be based on a comparison to a control. In some embodiments, the control is a known standard obtained from the literature (e.g., a known gene sequence, RNA sequence, protein sequence, gene expression level). In some embodiments, the control is a control sample obtained from an individual to be treated or being treated using the methods disclosed herein (e.g., a control sample from a non-cancerous tissue). In some embodiments, the control is a control sample obtained from an individual other than the individual to be treated or being treated using the methods disclosed herein (e.g., a control sample from a healthy volunteer or a volunteer without cancer). In some embodiments, the control is obtained from a given patient population. For example, with respect to the level of gene expression or enzyme activity level, the control level may be the median expression level of that gene for the patient population, or the median enzyme activity level of that enzyme. And, for example, if the expression level of the gene of interest in one patient is determined to be above the median expression level of the patient population, the patient is determined to have high expression of the gene of interest. Alternatively, a patient is determined to have low expression of a gene of interest if the expression level of the gene of interest in the patient is determined to be lower than the median expression level of the patient population. In some embodiments, the patient has a disease (such as cancer) and the patient population does not have the disease. In some embodiments, the patient and the patient population have the same histological type of disease. The population can be about or at least about 2, 5, 10, 15, 20, 25, 30, 50, 60, 75, 100, 125, 150, 175, 200, 225, 250, 300, 400, 500 in terms of the number of individuals measured. Preferably, a sufficient number of individuals are measured to provide a statistically significant population that can be determined by methods known in the art, hi some embodiments, the population is a group participating in a clinical trial.
[0047] As used herein, the terms "comprising," "having," "containing," and "including," and other similar forms and their grammatical equivalents, are intended to be equivalent in meaning and open ended in that the item or items following any one of these words are not meant to imply a limited enumeration of such item or items, but are not meant to be limited to only the item or items listed. For example, an article "comprising" components A, B, and C may be composed of (i.e., include only) components A, B, and C, or may include not only components A, B, and C, but also one or more other components. Thus, "comprising" and similar forms and their grammatical equivalents are intended and understood to include disclosure of embodiments that "consist essentially of" or "consist of."
[0048] Where a range of values is provided, it is understood that each intervening value, to the tenth of the unit of the lower limit, between the upper and lower limit of that range and any other stated or intervening value in that stated range, is included within the disclosure, subject to any specifically excluded limit in the stated range, unless the context clearly dictates otherwise. Where the stated range includes one or both of the limits, ranges excluding either or both of those included limits are also included in the disclosure.
[0049] Reference herein to a value or parameter preceded by "about" includes (and describes) the variation relative to that value or parameter itself. For example, a reference to "about X" includes the reference to "X."
[0050] As used herein, including the appended claims, the singular forms "a," "or," and "the" include plural referents unless the context clearly dictates otherwise.
[0051] [Antigenic composition containing labyrinthin-derived peptide] The present application provides, in some aspects, antigenic compositions comprising one or more labyrinthin-derived peptides. Labyrinthin is a protein having a 255 amino acid sequence set forth in SEQ ID NO:1 (shown in Table 1). Transcriptional variants related to labyrinthin are known, including junctate, humbug, and human aspartyl beta-hydroxylase (HAAH) (see, e.g., U.S. Patent No. 6,166,176, which is incorporated herein by reference in its entirety). JPEG2025072379000002.jpg98162
[0052] The antigenic compositions disclosed herein comprise one or more labyrinthin-derived peptides described herein that are based, in whole or in part, on the sequence of labyrinthin (SEQ ID NO: 1). In some embodiments, the antigenic compositions comprise a labyrinthin-derived peptide that comprises a T cell epitope and / or a B cell epitope.
[0053] In some embodiments, the antigenic composition comprises at least two, e.g., at least any of 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15, labyrinthin-derived peptides. In some embodiments, the labyrinthin-derived peptides described herein have one or more of the following properties: they can be easily synthesized, e.g., on a commercial scale, are soluble, e.g., in aqueous solution, have a low pI (e.g., less than about 3.6, e.g., less than any of about 3.4 or about 3.3), have a desired charge, e.g., a low charge, bind to complexes such as MHC, are processed by cells for presentation, demonstrate in vivo presentation, and trigger an immune response. Additionally, in some embodiments, the labyrinthin-derived peptides and compositions thereof, e.g., antigenic compositions and / or vaccine compositions, described herein, are freeze-thaw stable, e.g., less than 15% of the labyrinthin-derived peptides are degraded over the course of at least three freeze-thaw cycles. In some embodiments, the labyrinthin-derived peptides and compositions thereof, such as antigenic and / or vaccine compositions, described herein, are stable at room temperature, e.g., less than 15% of the labyrinthin-derived peptide is degraded upon incubation at room temperature for at least 6 hours. In some embodiments, the labyrinthin-derived peptide is a peptide having at least about 60% sequence similarity, e.g., at least about 65% similarity, 70% similarity, 75% similarity, 80% similarity, 85% similarity, 90% similarity, or 95% similarity, to a portion of labyrinthin (SEQ ID NO:1), where the labyrinthin-derived peptide does not include a terminal proline residue, and where the labyrinthin-derived peptide includes at least one proline residue, e.g., 2, 3, 4, or 5 proline residues. In some embodiments, the labyrinthin-derived peptide is a peptide having at least about 60% sequence similarity, e.g., at least about 65% similarity, 70% similarity, 75% similarity, 80% similarity, 85% similarity, 90% similarity, or 95% similarity, to a portion of labyrinthin (SEQ ID NO:1), where one end of the labyrinthin-derived peptide does not include a terminal proline residue, and the labyrinthin-derived peptide includes at least one proline residue, e.g., 2, 3, 4, or 5 proline residues.In some embodiments, the labyrinthin derived peptide is 7 to 50 amino acids in length, e.g., 7 to 25 amino acids in length, 7 to 13 amino acids in length, or 21 to 25 amino acids in length. In some embodiments, the labyrinthin derived peptide is 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50 amino acids in length. In some embodiments, the labyrinthin-derived peptide has at least about 60% sequence similarity to a portion of labyrinthin (SEQ ID NO:1), such as at least about 65%, 70%, 75%, 80%, 85%, 90%, or 95% similarity. In some embodiments, the labyrinthin-derived peptide or derivative thereof has at least about 60% sequence similarity to a portion of labyrinthin (SEQ ID NO:1), where 1, 2, 3, 4, 5 amino acids of the labyrinthin-derived peptide sequence are deleted, substituted, inserted, and / or added to the labyrinthin-derived peptide, and where there is a substitution, insertion, and / or addition, a portion is substituted, inserted, and / or added to the sequence. In some embodiments, the substituted, inserted, or added portion is a natural amino acid (e.g., an α-amino acid or an L-amino acid or a D-amino acid) or a non-natural amino acid. In some embodiments, the substituted, inserted or added moiety is an amino acid replacement or a linker. In some embodiments, the labyrinthin derived peptide has a pI between about 3.4 and about 3.1, such as about 3.3 and about 3.15. In some embodiments, the labyrinthin derived peptide has a pI less than about 3.4.
[0054] In some embodiments, the antigenic composition comprises a labyrinthin-derived peptide comprising a sequence selected from SEQ ID NOs:2-32 (Table 2), or a variant thereof. In some embodiments, the labyrinthin-derived peptide comprising a sequence selected from SEQ ID NOs:2-32 (Table 2), or a variant thereof, comprises one or two contiguous amino acid sequences added to the ends of a core sequence provided in SEQ ID NOs:2-32. In some embodiments, the labyrinthin-derived peptide comprising one or two contiguous amino acid sequences is a peptide having at least about 60% similarity to a portion of labyrinthin (SEQ ID NO:1), e.g., at least about 65% similarity, 70% similarity, 75% similarity, 80% similarity, 85% similarity, 90% similarity, or 95% similarity. In some embodiments, the flanking amino acid sequences are based on the sequence of a portion of Labyrinthin (SEQ ID NO:1) and are respective continuations of the Labyrinthin sequence from each of the core sequences provided in SEQ ID NOs:2-32, e.g., from one or two ends of the core sequence. For example, in the case of SEQ ID NO:3, the first flanking amino acid sequence of the two amino acids to the left of SEQ ID NO:3 is Pro-Ala, and the second flanking amino acid sequence of the two amino acids to the right of SEQ ID NO:3 is Glu-Ala. JPEG2025072379000003.jpg201168
[0055] In some embodiments, the antigenic composition comprises a labyrinthin-derived peptide comprising SEQ ID NO:2 or a variant thereof, wherein the labyrinthin-derived peptide comprises a T cell epitope and / or a B cell epitope. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:2 or a variant thereof, wherein the labyrinthin-derived peptide is 7 to 50 amino acids in length, e.g., 7 to 25 amino acids in length, 7 to 13 amino acids in length, or 21 to 25 amino acids in length. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:2 or a variant thereof, wherein the labyrinthin-derived peptide has at least about 60% sequence similarity to a portion of labyrinthin (SEQ ID NO:1), e.g., at least about 65% similarity, 70% similarity, 75% similarity, 80% similarity, 85% similarity, 90% similarity, or 95% similarity. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:2 or a variant thereof, where one or two amino acids of the sequence of SEQ ID NO:2 are deleted, substituted, inserted, and / or added to the labyrinthin-derived peptide, and where there is a substitution, insertion, and / or addition, a moiety is substituted, inserted, and / or added to the sequence. In some embodiments, the substituted, inserted, or added moiety is a natural amino acid (e.g., an α-amino acid or an L-amino acid or a D-amino acid) or a non-natural amino acid. In some embodiments, the substituted, inserted, or added moiety is an amino acid substitute or a linker.
[0056] In some embodiments, the antigenic composition comprises a labyrinthin-derived peptide comprising SEQ ID NO:3 or a variant thereof, wherein the labyrinthin-derived peptide comprises a T cell epitope and / or a B cell epitope. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:3 or a variant thereof, wherein the labyrinthin-derived peptide is 7 to 50 amino acids in length, e.g., 7 to 25 amino acids in length, 7 to 13 amino acids in length, or 21 to 25 amino acids in length. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:3 or a variant thereof, wherein the labyrinthin-derived peptide has at least about 60% sequence similarity to a portion of labyrinthin (SEQ ID NO:1), e.g., at least about 65% similarity, 70% similarity, 75% similarity, 80% similarity, 85% similarity, 90% similarity, or 95% similarity. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:3 or a variant thereof, where one or two amino acids of the sequence of SEQ ID NO:3 are deleted, substituted, inserted, and / or added to the labyrinthin-derived peptide, and where there is a substitution, insertion, and / or addition, a moiety is substituted, inserted, and / or added to the sequence. In some embodiments, the substituted, inserted, or added moiety is a natural amino acid (e.g., an α-amino acid or an L-amino acid or a D-amino acid) or a non-natural amino acid. In some embodiments, the substituted, inserted, or added moiety is an amino acid substitute or a linker.
[0057] In some embodiments, the antigenic composition comprises a labyrinthin-derived peptide comprising SEQ ID NO:4 or a variant thereof, wherein the labyrinthin-derived peptide comprises a T cell epitope and / or a B cell epitope. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:4 or a variant thereof, wherein the labyrinthin-derived peptide is 7 to 50 amino acids in length, e.g., 7 to 25 amino acids in length, 7 to 13 amino acids in length, or 21 to 25 amino acids in length. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:4 or a variant thereof, wherein the labyrinthin-derived peptide has at least about 60% sequence similarity to a portion of labyrinthin (SEQ ID NO:1), e.g., at least about 65% similarity, 70% similarity, 75% similarity, 80% similarity, 85% similarity, 90% similarity, or 95% similarity. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:4 or a variant thereof, where one or two amino acids of the sequence of SEQ ID NO:4 are deleted, substituted, inserted, and / or added to the labyrinthin-derived peptide, and where there is a substitution, insertion, and / or addition, a moiety is substituted, inserted, and / or added to the sequence. In some embodiments, the substituted, inserted, or added moiety is a natural amino acid (e.g., an α-amino acid or an L-amino acid or a D-amino acid) or a non-natural amino acid. In some embodiments, the substituted, inserted, or added moiety is an amino acid substitute or a linker.
[0058] In some embodiments, the antigenic composition comprises a labyrinthin-derived peptide comprising SEQ ID NO:5 or a variant thereof, wherein the labyrinthin-derived peptide comprises a T cell epitope and / or a B cell epitope. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:5 or a variant thereof, wherein the labyrinthin-derived peptide is 7 to 50 amino acids in length, e.g., 7 to 25 amino acids in length, or 7 to 13 amino acids in length, or 21 to 25 amino acids in length. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:5 or a variant thereof, wherein the labyrinthin-derived peptide has at least about 60% sequence similarity to a portion of labyrinthin (SEQ ID NO:1), e.g., at least about 65% similarity, 70% similarity, 75% similarity, 80% similarity, 85% similarity, 90% similarity, or 95% similarity. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:5 or a variant thereof, where one or two amino acids of the sequence of SEQ ID NO:5 are deleted, substituted, inserted, and / or added to the labyrinthin-derived peptide, and where there is a substitution, insertion, and / or addition, a moiety is substituted, inserted, and / or added to the sequence. In some embodiments, the substituted, inserted, or added moiety is a natural amino acid (e.g., an α-amino acid or an L-amino acid or a D-amino acid) or a non-natural amino acid. In some embodiments, the substituted, inserted, or added moiety is an amino acid substitute or a linker.
[0059] In some embodiments, the antigenic composition comprises a labyrinthin-derived peptide comprising SEQ ID NO:7 or a variant thereof, wherein the labyrinthin-derived peptide comprises a T cell epitope and / or a B cell epitope. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:7 or a variant thereof, wherein the labyrinthin-derived peptide is 7 to 50 amino acids in length, e.g., 7 to 25 amino acids in length, or 7 to 13 amino acids in length, or 21 to 25 amino acids in length. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:7 or a variant thereof, wherein the labyrinthin-derived peptide has at least about 60% sequence similarity to a portion of labyrinthin (SEQ ID NO:1), e.g., at least about 65% similarity, 70% similarity, 75% similarity, 80% similarity, 85% similarity, 90% similarity, or 95% similarity. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:7 or a variant thereof, where one or two amino acids of the sequence of SEQ ID NO:7 are deleted, substituted, inserted, and / or added to the labyrinthin-derived peptide, and where there is a substitution, insertion, and / or addition, a moiety is substituted, inserted, and / or added to the sequence. In some embodiments, the substituted, inserted, or added moiety is a natural amino acid (e.g., an α-amino acid or an L-amino acid or a D-amino acid) or a non-natural amino acid. In some embodiments, the substituted, inserted, or added moiety is an amino acid substitute or a linker.
[0060] In some embodiments, the antigenic composition comprises a labyrinthin-derived peptide comprising SEQ ID NO:8 or a variant thereof, wherein the labyrinthin-derived peptide comprises a T cell epitope and / or a B cell epitope. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:8 or a variant thereof, wherein the labyrinthin-derived peptide is 7 to 50 amino acids in length, e.g., 7 to 25 amino acids in length, or 7 to 13 amino acids in length, or 21 to 25 amino acids in length. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:8 or a variant thereof, wherein the labyrinthin-derived peptide has at least about 60% sequence similarity to a portion of labyrinthin (SEQ ID NO:1), e.g., at least about 65% similarity, 70% similarity, 75% similarity, 80% similarity, 85% similarity, 90% similarity, or 95% similarity. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:8 or a variant thereof, where one or two amino acids of the sequence of SEQ ID NO:8 are deleted, substituted, inserted, and / or added to the labyrinthin-derived peptide, and where there is a substitution, insertion, and / or addition, a moiety is substituted, inserted, and / or added to the sequence. In some embodiments, the substituted, inserted, or added moiety is a natural amino acid (e.g., an α-amino acid or an L-amino acid or a D-amino acid) or a non-natural amino acid. In some embodiments, the substituted, inserted, or added moiety is an amino acid substitute or a linker.
[0061] In some embodiments, the antigenic composition comprises a labyrinthin-derived peptide comprising SEQ ID NO:9 or a variant thereof, wherein the labyrinthin-derived peptide comprises a T cell epitope and / or a B cell epitope. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:9 or a variant thereof, wherein the labyrinthin-derived peptide is 7 to 50 amino acids in length, e.g., 7 to 25 amino acids in length, or 7 to 13 amino acids in length, or 21 to 25 amino acids in length. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:9 or a variant thereof, wherein the labyrinthin-derived peptide has at least about 60% sequence similarity to a portion of labyrinthin (SEQ ID NO:1), e.g., at least about 65% similarity, 70% similarity, 75% similarity, 80% similarity, 85% similarity, 90% similarity, or 95% similarity. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:9 or a variant thereof, where one or two amino acids of the sequence of SEQ ID NO:9 are deleted, substituted, inserted, and / or added to the labyrinthin-derived peptide, and where there is a substitution, insertion, and / or addition, a moiety is substituted, inserted, and / or added to the sequence. In some embodiments, the substituted, inserted, or added moiety is a natural amino acid (e.g., an α-amino acid or an L-amino acid or a D-amino acid) or a non-natural amino acid. In some embodiments, the substituted, inserted, or added moiety is an amino acid substitute or a linker.
[0062] In some embodiments, the antigenic composition comprises a labyrinthin-derived peptide comprising SEQ ID NO:10 or a variant thereof, wherein the labyrinthin-derived peptide comprises a T cell epitope and / or a B cell epitope. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:10 or a variant thereof, wherein the labyrinthin-derived peptide is 7 to 50 amino acids in length, e.g., 7 to 25 amino acids in length, or 7 to 13 amino acids in length, or 21 to 25 amino acids in length. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:10 or a variant thereof, wherein the labyrinthin-derived peptide has at least about 60% sequence similarity to a portion of labyrinthin (SEQ ID NO:1), e.g., at least about 65% similarity, 70% similarity, 75% similarity, 80% similarity, 85% similarity, 90% similarity, or 95% similarity. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:10 or a variant thereof, where one or two amino acids of the sequence of SEQ ID NO:10 are deleted, substituted, inserted, and / or added to the labyrinthin-derived peptide, and where there is a substitution, insertion, and / or addition, a moiety is substituted, inserted, and / or added to the sequence. In some embodiments, the substituted, inserted, or added moiety is a natural amino acid (e.g., an α-amino acid or an L-amino acid or a D-amino acid) or a non-natural amino acid. In some embodiments, the substituted, inserted, or added moiety is an amino acid substitute or a linker.
[0063] In some embodiments, the antigenic composition comprises a labyrinthin-derived peptide comprising SEQ ID NO:11 or a variant thereof, wherein the labyrinthin-derived peptide comprises a T cell epitope and / or a B cell epitope. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:11 or a variant thereof, wherein the labyrinthin-derived peptide is 7 to 50 amino acids in length, e.g., 7 to 25 amino acids in length, or 7 to 13 amino acids in length, or 21 to 25 amino acids in length. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:11 or a variant thereof, wherein the labyrinthin-derived peptide has at least about 60% sequence similarity to a portion of labyrinthin (SEQ ID NO:1), e.g., at least about 65% similarity, 70% similarity, 75% similarity, 80% similarity, 85% similarity, 90% similarity, or 95% similarity. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:11 or a variant thereof, where one or two amino acids of the sequence of SEQ ID NO:11 are deleted, substituted, inserted, and / or added to the labyrinthin-derived peptide, and where there is a substitution, insertion, and / or addition, a moiety is substituted, inserted, and / or added to the sequence. In some embodiments, the substituted, inserted, or added moiety is a natural amino acid (e.g., an α-amino acid or an L-amino acid or a D-amino acid) or a non-natural amino acid. In some embodiments, the substituted, inserted, or added moiety is an amino acid substitute or a linker.
[0064] In some embodiments, the antigenic composition comprises a labyrinthin-derived peptide comprising SEQ ID NO:12 or a variant thereof, wherein the labyrinthin-derived peptide comprises a T cell epitope and / or a B cell epitope. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:12 or a variant thereof, wherein the labyrinthin-derived peptide is 7 to 50 amino acids in length, e.g., 7 to 25 amino acids in length, or 7 to 13 amino acids in length, or 21 to 25 amino acids in length. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:12 or a variant thereof, wherein the labyrinthin-derived peptide has at least about 60% sequence similarity to a portion of labyrinthin (SEQ ID NO:1), e.g., at least about 65% similarity, 70% similarity, 75% similarity, 80% similarity, 85% similarity, 90% similarity, or 95% similarity. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:12 or a variant thereof, where one or two amino acids of the sequence of SEQ ID NO:12 are deleted, substituted, inserted, and / or added to the labyrinthin-derived peptide, and where there is a substitution, insertion, and / or addition, a moiety is substituted, inserted, and / or added to the sequence. In some embodiments, the substituted, inserted, or added moiety is a natural amino acid (e.g., an α-amino acid or an L-amino acid or a D-amino acid) or a non-natural amino acid. In some embodiments, the substituted, inserted, or added moiety is an amino acid substitute or a linker.
[0065] In some embodiments, the antigenic composition comprises a labyrinthin-derived peptide comprising SEQ ID NO: 13 or a variant thereof, wherein the labyrinthin-derived peptide comprises a T cell epitope and / or a B cell epitope. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO: 13 or a variant thereof, wherein the labyrinthin-derived peptide is 7 to 50 amino acids in length, e.g., 7 to 25 amino acids in length, or 7 to 13 amino acids in length, or 21 to 25 amino acids in length. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO: 13 or a variant thereof, wherein the labyrinthin-derived peptide has at least about 60% sequence similarity to a portion of labyrinthin (SEQ ID NO: 1), e.g., at least about 65% similarity, 70% similarity, 75% similarity, 80% similarity, 85% similarity, 90% similarity, or 95% similarity. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:13 or a variant thereof, where one or two amino acids of the sequence of SEQ ID NO:13 are deleted, substituted, inserted, and / or added to the labyrinthin-derived peptide, and where there is a substitution, insertion, and / or addition, a moiety is substituted, inserted, and / or added to the sequence. In some embodiments, the substituted, inserted, or added moiety is a natural amino acid (e.g., an α-amino acid or an L-amino acid or a D-amino acid) or a non-natural amino acid. In some embodiments, the substituted, inserted, or added moiety is an amino acid substitute or a linker.
[0066] In some embodiments, the antigenic composition comprises a labyrinthin-derived peptide comprising SEQ ID NO: 14 or a variant thereof, wherein the labyrinthin-derived peptide comprises a T cell epitope and / or a B cell epitope. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO: 14 or a variant thereof, wherein the labyrinthin-derived peptide is 7 to 50 amino acids in length, e.g., 7 to 25 amino acids in length, or 7 to 13 amino acids in length, or 21 to 25 amino acids in length. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO: 14 or a variant thereof, wherein the labyrinthin-derived peptide has at least about 60% sequence similarity to a portion of labyrinthin (SEQ ID NO: 1), e.g., at least about 65% similarity, 70% similarity, 75% similarity, 80% similarity, 85% similarity, 90% similarity, or 95% similarity. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:14 or a variant thereof, where one or two amino acids of the sequence of SEQ ID NO:14 are deleted, substituted, inserted, and / or added to the labyrinthin-derived peptide, and where there is a substitution, insertion, and / or addition, a moiety is substituted, inserted, and / or added to the sequence. In some embodiments, the substituted, inserted, or added moiety is a natural amino acid (e.g., an α-amino acid or an L-amino acid or a D-amino acid) or a non-natural amino acid. In some embodiments, the substituted, inserted, or added moiety is an amino acid substitute or a linker.
[0067] In some embodiments, the antigenic composition comprises a labyrinthin-derived peptide comprising SEQ ID NO:15 or a variant thereof, wherein the labyrinthin-derived peptide comprises a T cell epitope and / or a B cell epitope. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:15 or a variant thereof, wherein the labyrinthin-derived peptide is 7 to 50 amino acids in length, e.g., 7 to 25 amino acids in length, or 7 to 13 amino acids in length, or 21 to 25 amino acids in length. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:15 or a variant thereof, wherein the labyrinthin-derived peptide has at least about 60% sequence similarity to a portion of labyrinthin (SEQ ID NO:1), e.g., at least about 65% similarity, 70% similarity, 75% similarity, 80% similarity, 85% similarity, 90% similarity, or 95% similarity. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:15 or a variant thereof, where one or two amino acids of the sequence of SEQ ID NO:15 are deleted, substituted, inserted, and / or added to the labyrinthin-derived peptide, and where there is a substitution, insertion, and / or addition, a moiety is substituted, inserted, and / or added to the sequence. In some embodiments, the substituted, inserted, or added moiety is a natural amino acid (e.g., an α-amino acid or an L-amino acid or a D-amino acid) or a non-natural amino acid. In some embodiments, the substituted, inserted, or added moiety is an amino acid substitute or a linker.
[0068] In some embodiments, the antigenic composition comprises a labyrinthin-derived peptide comprising SEQ ID NO: 16 or a variant thereof, wherein the labyrinthin-derived peptide comprises a T cell epitope and / or a B cell epitope. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO: 16 or a variant thereof, wherein the labyrinthin-derived peptide is 7 to 50 amino acids in length, e.g., 7 to 25 amino acids in length, or 7 to 13 amino acids in length, or 21 to 25 amino acids in length. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO: 16 or a variant thereof, wherein the labyrinthin-derived peptide has at least about 60% sequence similarity to a portion of labyrinthin (SEQ ID NO: 1), e.g., at least about 65% similarity, 70% similarity, 75% similarity, 80% similarity, 85% similarity, 90% similarity, or 95% similarity. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:16 or a variant thereof, where one, two or three amino acids of the sequence of SEQ ID NO:16 are deleted, substituted, inserted and / or added to the labyrinthin-derived peptide, and where there is a substitution, insertion and / or addition, a moiety is substituted, inserted and / or added to the sequence. In some embodiments, the substituted, inserted or added moiety is a natural amino acid (e.g., an α-amino acid or an L-amino acid or a D-amino acid) or a non-natural amino acid. In some embodiments, the substituted, inserted or added moiety is an amino acid substitute or a linker.
[0069] In some embodiments, the antigenic composition comprises a labyrinthin-derived peptide comprising SEQ ID NO:17 or a variant thereof, wherein the labyrinthin-derived peptide comprises a T cell epitope and / or a B cell epitope. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:17 or a variant thereof, wherein the labyrinthin-derived peptide is 9 to 50 amino acids in length, e.g., 9 to 25 amino acids in length, or 9 to 13 amino acids in length, or 21 to 25 amino acids in length. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:17 or a variant thereof, wherein the labyrinthin-derived peptide has at least about 60% sequence similarity to a portion of labyrinthin (SEQ ID NO:1), e.g., at least about 65% similarity, 70% similarity, 75% similarity, 80% similarity, 85% similarity, 90% similarity, or 95% similarity. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:17 or a variant thereof, where one, two or three amino acids of the sequence of SEQ ID NO:17 are deleted, substituted, inserted and / or added to the labyrinthin-derived peptide, and where there is a substitution, insertion and / or addition, a moiety is substituted, inserted and / or added to the sequence. In some embodiments, the substituted, inserted or added moiety is a natural amino acid (e.g., an α-amino acid or an L-amino acid or a D-amino acid) or a non-natural amino acid. In some embodiments, the substituted, inserted or added moiety is an amino acid substitute or a linker.
[0070] In some embodiments, the antigenic composition comprises a labyrinthin-derived peptide comprising SEQ ID NO:18 or a variant thereof, wherein the labyrinthin-derived peptide comprises a T cell epitope and / or a B cell epitope. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:18 or a variant thereof, wherein the labyrinthin-derived peptide is 7 to 50 amino acids in length, e.g., 7 to 25 amino acids in length, or 7 to 13 amino acids in length, or 21 to 25 amino acids in length. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:18 or a variant thereof, wherein the labyrinthin-derived peptide has at least about 60% sequence similarity to a portion of labyrinthin (SEQ ID NO:1), e.g., at least about 65% similarity, 70% similarity, 75% similarity, 80% similarity, 85% similarity, 90% similarity, or 95% similarity. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:18 or a variant thereof, where one, two or three amino acids of the sequence of SEQ ID NO:18 are deleted, substituted, inserted and / or added to the labyrinthin-derived peptide, and where there is a substitution, insertion and / or addition, a moiety is substituted, inserted and / or added to the sequence. In some embodiments, the substituted, inserted or added moiety is a natural amino acid (e.g., an α-amino acid or an L-amino acid or a D-amino acid) or a non-natural amino acid. In some embodiments, the substituted, inserted or added moiety is an amino acid substitute or a linker.
[0071] In some embodiments, the antigenic composition comprises a labyrinthin-derived peptide comprising SEQ ID NO:19 or a variant thereof, wherein the labyrinthin-derived peptide comprises a T cell epitope and / or a B cell epitope. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:19 or a variant thereof, wherein the labyrinthin-derived peptide is 8 to 50 amino acids in length, e.g., 10 to 25 amino acids in length, or 8 to 13 amino acids in length, or 21 to 25 amino acids in length. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:19 or a variant thereof, wherein the labyrinthin-derived peptide has at least about 60% sequence similarity to a portion of labyrinthin (SEQ ID NO:1), e.g., at least about 65% similarity, 70% similarity, 75% similarity, 80% similarity, 85% similarity, 90% similarity, or 95% similarity. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:19 or a variant thereof, where one, two or three amino acids of the sequence of SEQ ID NO:19 are deleted, substituted, inserted and / or added to the labyrinthin-derived peptide, and where there is a substitution, insertion and / or addition, a moiety is substituted, inserted and / or added to the sequence. In some embodiments, the substituted, inserted or added moiety is a natural amino acid (e.g., an α-amino acid or an L-amino acid or a D-amino acid) or a non-natural amino acid. In some embodiments, the substituted, inserted or added moiety is an amino acid substitute or a linker.
[0072] In some embodiments, the antigenic composition comprises a labyrinthin-derived peptide comprising SEQ ID NO:20 or a variant thereof, wherein the labyrinthin-derived peptide comprises a T cell epitope and / or a B cell epitope. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:20 or a variant thereof, wherein the labyrinthin-derived peptide is 8 to 50 amino acids in length, e.g., 10 to 25 amino acids in length, or 8 to 13 amino acids in length, or 21 to 25 amino acids in length. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:20 or a variant thereof, wherein the labyrinthin-derived peptide has at least about 60% sequence similarity to a portion of labyrinthin (SEQ ID NO:1), e.g., at least about 65% similarity, 70% similarity, 75% similarity, 80% similarity, 85% similarity, 90% similarity, or 95% similarity. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:20 or a variant thereof, where one, two or three amino acids of the sequence of SEQ ID NO:20 are deleted, substituted, inserted and / or added to the labyrinthin-derived peptide, and where there is a substitution, insertion and / or addition, a moiety is substituted, inserted and / or added to the sequence. In some embodiments, the substituted, inserted or added moiety is a natural amino acid (e.g., an α-amino acid or an L-amino acid or a D-amino acid) or a non-natural amino acid. In some embodiments, the substituted, inserted or added moiety is an amino acid substitute or a linker.
[0073] In some embodiments, the antigenic composition comprises a labyrinthin-derived peptide comprising SEQ ID NO:21 or a variant thereof, wherein the labyrinthin-derived peptide comprises a T cell epitope and / or a B cell epitope. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:21 or a variant thereof, wherein the labyrinthin-derived peptide is 7 to 50 amino acids in length, e.g., 7 to 25 amino acids in length, or 7 to 13 amino acids in length, or 21 to 25 amino acids in length. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:21 or a variant thereof, wherein the labyrinthin-derived peptide has at least about 60% sequence similarity to a portion of labyrinthin (SEQ ID NO:1), e.g., at least about 65% similarity, 70% similarity, 75% similarity, 80% similarity, 85% similarity, 90% similarity, or 95% similarity. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:21 or a variant thereof, where one, two or three amino acids of the sequence of SEQ ID NO:21 are deleted, substituted, inserted and / or added to the labyrinthin-derived peptide, and where there is a substitution, insertion and / or addition, a moiety is substituted, inserted and / or added to the sequence. In some embodiments, the substituted, inserted or added moiety is a natural amino acid (e.g., an α-amino acid or an L-amino acid or a D-amino acid) or a non-natural amino acid. In some embodiments, the substituted, inserted or added moiety is an amino acid substitute or a linker.
[0074] In some embodiments, the antigenic composition comprises a labyrinthin-derived peptide comprising SEQ ID NO:22 or a variant thereof, wherein the labyrinthin-derived peptide comprises a T cell epitope and / or a B cell epitope. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:22 or a variant thereof, wherein the labyrinthin-derived peptide is 8 to 50 amino acids in length, e.g., 10 to 25 amino acids in length, or 8 to 13 amino acids in length, or 21 to 25 amino acids in length. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:22 or a variant thereof, wherein the labyrinthin-derived peptide has at least about 60% sequence similarity to a portion of labyrinthin (SEQ ID NO:1), e.g., at least about 65% similarity, 70% similarity, 75% similarity, 80% similarity, 85% similarity, 90% similarity, or 95% similarity. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:22 or a variant thereof, where one, two or three amino acids of the sequence of SEQ ID NO:22 are deleted, substituted, inserted and / or added to the labyrinthin-derived peptide, and where there is a substitution, insertion and / or addition, a moiety is substituted, inserted and / or added to the sequence. In some embodiments, the substituted, inserted or added moiety is a natural amino acid (e.g., an α-amino acid or an L-amino acid or a D-amino acid) or a non-natural amino acid. In some embodiments, the substituted, inserted or added moiety is an amino acid substitute or a linker.
[0075] In some embodiments, the antigenic composition comprises a labyrinthin-derived peptide comprising SEQ ID NO:23 or a variant thereof, wherein the labyrinthin-derived peptide comprises a T cell epitope and / or a B cell epitope. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:23 or a variant thereof, wherein the labyrinthin-derived peptide is 8 to 50 amino acids in length, e.g., 10 to 25 amino acids in length, or 8 to 13 amino acids in length, or 21 to 25 amino acids in length. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:23 or a variant thereof, wherein the labyrinthin-derived peptide has at least about 60% sequence similarity to a portion of labyrinthin (SEQ ID NO:1), e.g., at least about 65% similarity, 70% similarity, 75% similarity, 80% similarity, 85% similarity, 90% similarity, or 95% similarity. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:23 or a variant thereof, where one, two or three amino acids of the sequence of SEQ ID NO:23 are deleted, substituted, inserted and / or added to the labyrinthin-derived peptide, and where there is a substitution, insertion and / or addition, a moiety is substituted, inserted and / or added to the sequence. In some embodiments, the substituted, inserted or added moiety is a natural amino acid (e.g., an α-amino acid or an L-amino acid or a D-amino acid) or a non-natural amino acid. In some embodiments, the substituted, inserted or added moiety is an amino acid substitute or a linker.
[0076] In some embodiments, the antigenic composition comprises a labyrinthin-derived peptide comprising SEQ ID NO:24 or a variant thereof, wherein the labyrinthin-derived peptide comprises a T cell epitope and / or a B cell epitope. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:24 or a variant thereof, wherein the labyrinthin-derived peptide is 12 to 50 amino acids in length, e.g., 12 to 25 amino acids in length, or 12 to 13 amino acids in length, or 21 to 25 amino acids in length. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:24 or a variant thereof, wherein the labyrinthin-derived peptide has at least about 60% sequence similarity to a portion of labyrinthin (SEQ ID NO:1), e.g., at least about 65% similarity, 70% similarity, 75% similarity, 80% similarity, 85% similarity, 90% similarity, or 95% similarity. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:24 or a variant thereof, where one, two or three amino acids of the sequence of SEQ ID NO:24 are deleted, substituted, inserted and / or added to the labyrinthin-derived peptide, and where there is a substitution, insertion and / or addition, a moiety is substituted, inserted and / or added to the sequence. In some embodiments, the substituted, inserted or added moiety is a natural amino acid (e.g., an α-amino acid or an L-amino acid or a D-amino acid) or a non-natural amino acid. In some embodiments, the substituted, inserted or added moiety is an amino acid substitute or a linker.
[0077] In some embodiments, the antigenic composition comprises a labyrinthin-derived peptide comprising SEQ ID NO:25 or a variant thereof, wherein the labyrinthin-derived peptide comprises a T cell epitope and a B cell epitope. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:25 or a variant thereof, wherein the labyrinthin-derived peptide is 11 to 50 amino acids in length, e.g., 11 to 25 amino acids in length, or 12 to 13 amino acids in length, or 21 to 25 amino acids in length. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:25 or a variant thereof, wherein the labyrinthin-derived peptide has at least about 60% sequence similarity to a portion of labyrinthin (SEQ ID NO:1), e.g., at least about 65% similarity, 70% similarity, 75% similarity, 80% similarity, 85% similarity, 90% similarity, or 95% similarity. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:25 or a variant thereof, where one, two or three amino acids of the sequence of SEQ ID NO:25 are deleted, substituted, inserted and / or added to the labyrinthin-derived peptide, and where there is a substitution, insertion and / or addition, a moiety is substituted, inserted and / or added to the sequence. In some embodiments, the substituted, inserted or added moiety is a natural amino acid (e.g., an α-amino acid or an L-amino acid or a D-amino acid) or a non-natural amino acid. In some embodiments, the substituted, inserted or added moiety is an amino acid substitute or a linker.
[0078] In some embodiments, the antigenic composition comprises a labyrinthin-derived peptide comprising SEQ ID NO:26 or a variant thereof, wherein the labyrinthin-derived peptide comprises a T cell epitope and a B cell epitope. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:26 or a variant thereof, wherein the labyrinthin-derived peptide is 11 to 50 amino acids in length, e.g., 11 to 25 amino acids in length, or 12 to 13 amino acids in length, or 21 to 25 amino acids in length. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:26 or a variant thereof, wherein the labyrinthin-derived peptide has at least about 60% sequence similarity to a portion of labyrinthin (SEQ ID NO:1), e.g., at least about 65% similarity, 70% similarity, 75% similarity, 80% similarity, 85% similarity, 90% similarity, or 95% similarity. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:26 or a variant thereof, where one, two or three amino acids of the sequence of SEQ ID NO:26 are deleted, substituted, inserted and / or added to the labyrinthin-derived peptide, and where there is a substitution, insertion and / or addition, a moiety is substituted, inserted and / or added to the sequence. In some embodiments, the substituted, inserted or added moiety is a natural amino acid (e.g., an α-amino acid or an L-amino acid or a D-amino acid) or a non-natural amino acid. In some embodiments, the substituted, inserted or added moiety is an amino acid substitute or a linker.
[0079] In some embodiments, the antigenic composition comprises a labyrinthin-derived peptide comprising SEQ ID NO:27 or a variant thereof, wherein the labyrinthin-derived peptide comprises a T cell epitope and a B cell epitope. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:27 or a variant thereof, wherein the labyrinthin-derived peptide is 11 to 50 amino acids in length, e.g., 11 to 25 amino acids in length, or 11 to 13 amino acids in length, or 21 to 25 amino acids in length. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:27 or a variant thereof, wherein the labyrinthin-derived peptide has at least about 60% sequence similarity to a portion of labyrinthin (SEQ ID NO:1), e.g., at least about 65% similarity, 70% similarity, 75% similarity, 80% similarity, 85% similarity, 90% similarity, or 95% similarity. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:27 or a variant thereof, where one, two or three amino acids of the sequence of SEQ ID NO:27 are deleted, substituted, inserted and / or added to the labyrinthin-derived peptide, and where there is a substitution, insertion and / or addition, a moiety is substituted, inserted and / or added to the sequence. In some embodiments, the substituted, inserted or added moiety is a natural amino acid (e.g., an α-amino acid or an L-amino acid or a D-amino acid) or a non-natural amino acid. In some embodiments, the substituted, inserted or added moiety is an amino acid substitute or a linker.
[0080] In some embodiments, the antigenic composition comprises a labyrinthin-derived peptide comprising SEQ ID NO:28 or a variant thereof, wherein the labyrinthin-derived peptide comprises a T cell epitope and / or a B cell epitope. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:28 or a variant thereof, wherein the labyrinthin-derived peptide is 10 to 50 amino acids in length, e.g., 10 to 25 amino acids in length, or 10 to 13 amino acids in length, or 21 to 25 amino acids in length. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:28 or a variant thereof, wherein the labyrinthin-derived peptide has at least about 60% sequence similarity to a portion of labyrinthin (SEQ ID NO:1), e.g., at least about 65% similarity, 70% similarity, 75% similarity, 80% similarity, 85% similarity, 90% similarity, or 95% similarity. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:28 or a variant thereof, where one, two or three amino acids of the sequence of SEQ ID NO:28 are deleted, substituted, inserted and / or added to the labyrinthin-derived peptide, and where there is a substitution, insertion and / or addition, a moiety is substituted, inserted and / or added to the sequence. In some embodiments, the substituted, inserted or added moiety is a natural amino acid (e.g., an α-amino acid or an L-amino acid or a D-amino acid) or a non-natural amino acid. In some embodiments, the substituted, inserted or added moiety is an amino acid substitute or a linker.
[0081] In some embodiments, the antigenic composition comprises a labyrinthin-derived peptide comprising SEQ ID NO:29 or a variant thereof, wherein the labyrinthin-derived peptide comprises a T cell epitope and a B cell epitope. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:29 or a variant thereof, wherein the labyrinthin-derived peptide is 22 to 50 amino acids in length. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:29 or a variant thereof, wherein the labyrinthin-derived peptide has at least about 60% sequence similarity to a portion of labyrinthin (SEQ ID NO:1), such as at least about 65% similarity, 70% similarity, 75% similarity, 80% similarity, 85% similarity, 90% similarity, or 95% similarity. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:29 or a variant thereof, where one, two, three, four, or five amino acids of the sequence of SEQ ID NO:29 are deleted, substituted, inserted, and / or added to the labyrinthin-derived peptide, and where there is a substitution, insertion, and / or addition, a moiety is substituted, inserted, and / or added to the sequence. In some embodiments, the substituted, inserted, or added moiety is a natural amino acid (e.g., an α-amino acid or an L-amino acid or a D-amino acid) or a non-natural amino acid. In some embodiments, the substituted, inserted, or added moiety is an amino acid substitute or a linker.
[0082] In some embodiments, the antigenic composition comprises a labyrinthin-derived peptide comprising SEQ ID NO:30 or a variant thereof, wherein the labyrinthin-derived peptide comprises a T cell epitope and a B cell epitope. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:30 or a variant thereof, wherein the labyrinthin-derived peptide is 22 to 50 amino acids in length. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:30 or a variant thereof, wherein the labyrinthin-derived peptide has at least about 60% sequence similarity to a portion of labyrinthin (SEQ ID NO:1), such as at least about 65% similarity, 70% similarity, 75% similarity, 80% similarity, 85% similarity, 90% similarity, or 95% similarity. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:30 or a variant thereof, where one, two, three, four, or five amino acids of the sequence of SEQ ID NO:30 are deleted, substituted, inserted, and / or added to the labyrinthin-derived peptide, and where there is a substitution, insertion, and / or addition, a moiety is substituted, inserted, and / or added to the sequence. In some embodiments, the substituted, inserted, or added moiety is a natural amino acid (e.g., an α-amino acid or an L-amino acid or a D-amino acid) or a non-natural amino acid. In some embodiments, the substituted, inserted, or added moiety is an amino acid substitute or a linker.
[0083] In some embodiments, the antigenic composition comprises a labyrinthin-derived peptide comprising SEQ ID NO:31 or a variant thereof, wherein the labyrinthin-derived peptide comprises a T cell epitope and a B cell epitope. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:31 or a variant thereof, wherein the labyrinthin-derived peptide is 22 to 50 amino acids in length. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:31 or a variant thereof, wherein the labyrinthin-derived peptide has at least about 60% sequence similarity to a portion of labyrinthin (SEQ ID NO:1), such as at least about 65% similarity, 70% similarity, 75% similarity, 80% similarity, 85% similarity, 90% similarity, or 95% similarity. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:31 or a variant thereof, where one, two, three, four, or five amino acids of the sequence of SEQ ID NO:31 are deleted, substituted, inserted, and / or added to the labyrinthin-derived peptide, and where there is a substitution, insertion, and / or addition, a moiety is substituted, inserted, and / or added to the sequence. In some embodiments, the substituted, inserted, or added moiety is a natural amino acid (e.g., an α-amino acid or an L-amino acid or a D-amino acid) or a non-natural amino acid. In some embodiments, the substituted, inserted, or added moiety is an amino acid substitute or a linker.
[0084] In some embodiments, the antigenic composition comprises a labyrinthin-derived peptide comprising SEQ ID NO:32 or a variant thereof, wherein the labyrinthin-derived peptide comprises a T cell epitope and a B cell epitope. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:32 or a variant thereof, wherein the labyrinthin-derived peptide is 23 to 50 amino acids in length. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:32 or a variant thereof, wherein the labyrinthin-derived peptide has at least about 60% sequence similarity to a portion of labyrinthin (SEQ ID NO:1), such as at least about 65% similarity, 70% similarity, 75% similarity, 80% similarity, 85% similarity, 90% similarity, or 95% similarity. In some embodiments, the labyrinthin-derived peptide comprises SEQ ID NO:32 or a variant thereof, where one, two, three, four, or five amino acids of the sequence of SEQ ID NO:32 are deleted, substituted, inserted, and / or added to the labyrinthin-derived peptide, and where there is a substitution, insertion, and / or addition, a moiety is substituted, inserted, and / or added to the sequence. In some embodiments, the substituted, inserted, or added moiety is a natural amino acid (e.g., an α-amino acid or an L-amino acid or a D-amino acid) or a non-natural amino acid. In some embodiments, the substituted, inserted, or added moiety is an amino acid substitute or a linker.
[0085] In some embodiments, the antigenic composition comprises one or more labyrinthin-derived peptides selected from the group consisting of: (a) a first peptide comprising SEQ ID NO:25 or a variant thereof; (b) a second peptide comprising SEQ ID NO:26 or a variant thereof; (c) a third peptide comprising SEQ ID NO:27 or a variant thereof; and (d) a fourth peptide comprising SEQ ID NO:28 or a variant thereof, wherein each peptide comprises a T cell epitope and a B cell epitope.
[0086] In some embodiments, the first peptide comprising SEQ ID NO:25 or a variant thereof is between 11 and 50 amino acids in length, e.g., between 11 and 45 amino acids in length, between 11 and 40 amino acids in length, between 11 and 35 amino acids in length, between 11 and 30 amino acids in length, between 11 and 25 amino acids in length, between 15 and 30 amino acids in length, between 20 and 30 amino acids in length, or between 21 and 25 amino acids in length. In some embodiments, the first peptide comprising SEQ ID NO:25 or a variant thereof is at least 11 amino acids in length, e.g., at least 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50 amino acids in length. In some embodiments, the first peptide comprising SEQ ID NO:25 or a variant thereof is 50 amino acids or less in length, e.g., 49 amino acids, 48 amino acids, 47 amino acids, 46 amino acids, 45 amino acids, 44 amino acids, 43 amino acids, 42 amino acids, 41 amino acids, 40 amino acids, 39 amino acids, 38 amino acids, 37 amino acids, 36 amino acids, 35 amino acids, 34 amino acids, 33 amino acids, 32 amino acids, 31 amino acids, 30 amino acids, 29 amino acids, 28 amino acids, 27 amino acids, 26 amino acids, 25 amino acids, 24 amino acids, 23 amino acids, 22 amino acids, 21 amino acids, 20 amino acids, 19 amino acids, 18 amino acids, 17 amino acids, 16 amino acids, or 15 amino acids or less in length.In some embodiments, the first peptide comprising SEQ ID NO:25 or a variant thereof is 11 amino acids long, 12 amino acids long, 13 amino acids long, 14 amino acids long, 15 amino acids long, 16 amino acids long, 17 amino acids long, 18 amino acids long, 19 amino acids long, 20 amino acids long, 21 amino acids long, 22 amino acids long, 23 amino acids long, 24 amino acids long, 25 amino acids long, 26 amino acids long, 27 amino acids long, 28 amino acids long, 29 amino acids long, 30 amino acids long, 31 amino acids long, 32 amino acids long, 33 amino acids long, 34 amino acids long, 35 amino acids long, 36 amino acids long, 37 amino acids long, 38 amino acids long, 39 amino acids long, 40 amino acids long, 41 amino acids long, 42 amino acids long, 43 amino acids long, 44 amino acids long, 45 amino acids long, 46 amino acids long, 47 amino acids long, 48 amino acids long, 49 amino acids, or 50 amino acids long.
[0087] In some embodiments, the first peptide comprises SEQ ID NO:25. In some embodiments, the first peptide comprising SEQ ID NO:25 is SEQ ID NO:29. In some embodiments, the first peptide comprising SEQ ID NO:25 or a variant thereof is a variant of SEQ ID NO:29, where at least one amino acid of the sequence of SEQ ID NO:29 is substituted, deleted, inserted, and / or added to the first peptide. In some embodiments, the first peptide comprising SEQ ID NO:25 or a variant thereof is a variant of SEQ ID NO:29, where one, two, three, four, or five amino acids of SEQ ID NO:29 are deleted, substituted, inserted, and / or added to the first peptide, and where there is a substitution, insertion, and / or addition, a moiety is substituted, inserted, and / or added to the sequence. In some embodiments, the substituted, inserted, or added moiety is a natural amino acid (e.g., an α-amino acid or an L-amino acid or a D-amino acid) or a non-natural amino acid. In some embodiments, the substituted, inserted, or added moiety is an amino acid substitute or a linker.
[0088] In some embodiments, the first peptide comprising SEQ ID NO:25 or a variant thereof is substantially homologous to a portion of labyrinthin (SEQ ID NO:1). In some embodiments, the first peptide comprising SEQ ID NO:25 or a variant thereof has at least about 60% sequence similarity to a portion of labyrinthin (SEQ ID NO:1), such as at least about 65%, 70%, 75%, 80%, 85%, 90%, or 95% similarity. In some embodiments, a variant of SEQ ID NO:29 has at least about 60% sequence similarity to a portion of labyrinthin (SEQ ID NO:1), such as at least about 65%, 70%, 75%, 80%, 85%, 90%, or 95% similarity.
[0089] In some embodiments, the second peptide comprising SEQ ID NO:26 or a variant thereof is between 12 and 50 amino acids in length, e.g., between 12 and 45 amino acids in length, between 12 and 40 amino acids in length, between 12 and 35 amino acids in length, between 12 and 30 amino acids in length, between 12 and 25 amino acids in length, between 15 and 30 amino acids in length, between 20 and 30 amino acids in length, or between 21 and 25 amino acids in length. In some embodiments, the second peptide comprising SEQ ID NO:26 or a variant thereof is at least 12 amino acids in length, e.g., at least 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50 amino acids in length. In some embodiments, the second peptide comprising SEQ ID NO:26 or a variant thereof is 50 amino acids or less in length, e.g., 49 amino acids, 48 amino acids, 47 amino acids, 46 amino acids, 45 amino acids, 44 amino acids, 43 amino acids, 42 amino acids, 41 amino acids, 40 amino acids, 39 amino acids, 38 amino acids, 37 amino acids, 36 amino acids, 35 amino acids, 34 amino acids, 33 amino acids, 32 amino acids, 31 amino acids, 30 amino acids, 29 amino acids, 28 amino acids, 27 amino acids, 26 amino acids, 25 amino acids, 24 amino acids, 23 amino acids, 22 amino acids, 21 amino acids, 20 amino acids, 19 amino acids, 18 amino acids, 17 amino acids, 16 amino acids, or 15 amino acids or less in length.In some embodiments, the second peptide comprising SEQ ID NO:26 or a variant thereof is 12 amino acids long, 13 amino acids long, 14 amino acids long, 15 amino acids long, 16 amino acids long, 17 amino acids long, 18 amino acids long, 19 amino acids long, 20 amino acids long, 21 amino acids long, 22 amino acids long, 23 amino acids long, 24 amino acids long, 25 amino acids long, 26 amino acids long, 27 amino acids long, 28 amino acids long, 29 amino acids long, 30 amino acids long, 31 amino acids long, 32 amino acids long, 33 amino acids long, 34 amino acids long, 35 amino acids long, 36 amino acids long, 37 amino acids long, 38 amino acids long, 39 amino acids long, 40 amino acids long, 41 amino acids long, 42 amino acids long, 43 amino acids long, 44 amino acids long, 45 amino acids long, 46 amino acids long, 47 amino acids long, 48 amino acids long, 49 amino acids, or 50 amino acids long.
[0090] In some embodiments, the second peptide comprises SEQ ID NO:26. In some embodiments, the second peptide comprising SEQ ID NO:26 is SEQ ID NO:30. In some embodiments, the second peptide comprising SEQ ID NO:26 or a variant thereof is a variant of SEQ ID NO:30, where at least one amino acid of the sequence of SEQ ID NO:26 is substituted, deleted, inserted, and / or added relative to the first peptide. In some embodiments, the second peptide comprising SEQ ID NO:26 or a variant thereof is a variant of SEQ ID NO:30, where one, two, three, four, or five amino acids of SEQ ID NO:30 are deleted, substituted, inserted, and / or added relative to the first peptide, and where there is a substitution, insertion, and / or addition, a moiety is substituted, inserted, and / or added relative to the sequence. In some embodiments, the substituted, inserted, or added moiety is a natural amino acid (e.g., an α-amino acid or an L-amino acid or a D-amino acid) or a non-natural amino acid. In some embodiments, the substituted, inserted, or added moiety is an amino acid substitute or a linker.
[0091] In some embodiments, the second peptide comprising SEQ ID NO:26 or a variant thereof is substantially homologous to a portion of labyrinthin (SEQ ID NO:1). In some embodiments, the second peptide comprising SEQ ID NO:26 or a variant thereof has at least about 60% sequence similarity to a portion of labyrinthin (SEQ ID NO:1), such as at least about 65%, 70%, 75%, 80%, 85%, 90%, or 95% similarity. In some embodiments, a variant of SEQ ID NO:30 has at least about 60% sequence similarity to a portion of labyrinthin (SEQ ID NO:1), such as at least about 65%, 70%, 75%, 80%, 85%, 90%, or 95% similarity.
[0092] In some embodiments, the third peptide comprising SEQ ID NO:27 or a variant thereof is between 11 and 50 amino acids in length, e.g., between 11 and 45 amino acids in length, between 11 and 40 amino acids in length, between 11 and 35 amino acids in length, between 11 and 30 amino acids in length, between 11 and 25 amino acids in length, between 15 and 30 amino acids in length, between 20 and 30 amino acids in length, or between 21 and 25 amino acids in length. In some embodiments, the third peptide comprising SEQ ID NO:27 or a variant thereof is at least 11 amino acids in length, e.g., at least 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50 amino acids in length. In some embodiments, the third peptide comprising SEQ ID NO:27 or a variant thereof is 50 amino acids or less in length, e.g., 49 amino acids, 48 amino acids, 47 amino acids, 46 amino acids, 45 amino acids, 44 amino acids, 43 amino acids, 42 amino acids, 41 amino acids, 40 amino acids, 39 amino acids, 38 amino acids, 37 amino acids, 36 amino acids, 35 amino acids, 34 amino acids, 33 amino acids, 32 amino acids, 31 amino acids, 30 amino acids, 29 amino acids, 28 amino acids, 27 amino acids, 26 amino acids, 25 amino acids, 24 amino acids, 23 amino acids, 22 amino acids, 21 amino acids, 20 amino acids, 19 amino acids, 18 amino acids, 17 amino acids, 16 amino acids, or 15 amino acids or less in length.In some embodiments, the third peptide comprising SEQ ID NO:27 or a variant thereof is 11 amino acids long, 12 amino acids long, 13 amino acids long, 14 amino acids long, 15 amino acids long, 16 amino acids long, 17 amino acids long, 18 amino acids long, 19 amino acids long, 20 amino acids long, 21 amino acids long, 22 amino acids long, 23 amino acids long, 24 amino acids long, 25 amino acids long, 26 amino acids long, 27 amino acids long, 28 amino acids long, 29 amino acids long, 30 amino acids long, 31 amino acids long, 32 amino acids long, 33 amino acids long, 34 amino acids long, 35 amino acids long, 36 amino acids long, 37 amino acids long, 38 amino acids long, 39 amino acids long, 40 amino acids long, 41 amino acids long, 42 amino acids long, 43 amino acids long, 44 amino acids long, 45 amino acids long, 46 amino acids long, 47 amino acids long, 48 amino acids long, 49 amino acids, or 50 amino acids long.
[0093] In some embodiments, the third peptide comprises SEQ ID NO:27. In some embodiments, the third peptide comprising SEQ ID NO:27 is SEQ ID NO:31. In some embodiments, the third peptide comprising SEQ ID NO:27 or a variant thereof is a variant of SEQ ID NO:31, where at least one amino acid of the sequence of SEQ ID NO:27 is substituted, deleted, inserted, and / or added relative to the first peptide. In some embodiments, the third peptide comprising SEQ ID NO:27 or a variant thereof is a variant of SEQ ID NO:31, where one, two, three, four, or five amino acids of SEQ ID NO:31 are deleted, substituted, inserted, and / or added relative to the first peptide, and where there is a substitution, insertion, and / or addition, a moiety is substituted, inserted, and / or added relative to the sequence. In some embodiments, the substituted, inserted, or added moiety is a natural amino acid (e.g., an α-amino acid or an L-amino acid or a D-amino acid) or a non-natural amino acid. In some embodiments, the substituted, inserted, or added moiety is an amino acid substitute or a linker.
[0094] In some embodiments, the third peptide comprising SEQ ID NO:27 or a variant thereof is substantially homologous to a portion of labyrinthin (SEQ ID NO:1). In some embodiments, the third peptide comprising SEQ ID NO:27 or a variant thereof has at least about 60% sequence similarity to a portion of labyrinthin (SEQ ID NO:1), such as at least about 65%, 70%, 75%, 80%, 85%, 90%, or 95% similarity. In some embodiments, a variant of SEQ ID NO:31 has at least about 60% sequence similarity to a portion of labyrinthin (SEQ ID NO:1), such as at least about 65%, 70%, 75%, 80%, 85%, 90%, or 95% similarity.
[0095] In some embodiments, the fourth peptide comprising SEQ ID NO:28 or a variant thereof is between 10 and 50 amino acids in length, e.g., between 10 and 45 amino acids in length, between 10 and 40 amino acids in length, between 10 and 35 amino acids in length, between 10 and 30 amino acids in length, between 10 and 25 amino acids in length, between 10 and 30 amino acids in length, between 20 and 30 amino acids in length, or between 21 and 25 amino acids in length. In some embodiments, the fourth peptide comprising SEQ ID NO:28 or a variant thereof is at least 10 amino acids in length, e.g., at least 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50 amino acids in length. In some embodiments, the fourth peptide comprising SEQ ID NO:28 or a variant thereof is 50 amino acids or less in length, e.g., 49 amino acids, 48 amino acids, 47 amino acids, 46 amino acids, 45 amino acids, 44 amino acids, 43 amino acids, 42 amino acids, 41 amino acids, 40 amino acids, 39 amino acids, 38 amino acids, 37 amino acids, 36 amino acids, 35 amino acids, 34 amino acids, 33 amino acids, 32 amino acids, 31 amino acids, 30 amino acids, 29 amino acids, 28 amino acids, 27 amino acids, 26 amino acids, 25 amino acids, 24 amino acids, 23 amino acids, 22 amino acids, 21 amino acids, 20 amino acids, 19 amino acids, 18 amino acids, 17 amino acids, 16 amino acids, or 15 amino acids or less in length.In some embodiments, the fourth peptide comprising SEQ ID NO:28 or a variant thereof is 10 amino acids long, 11 amino acids long, 12 amino acids long, 13 amino acids long, 14 amino acids long, 15 amino acids long, 16 amino acids long, 17 amino acids long, 18 amino acids long, 19 amino acids long, 20 amino acids long, 21 amino acids long, 22 amino acids long, 23 amino acids long, 24 amino acids long, 25 amino acids long, 26 amino acids long, 27 amino acids long, 28 amino acids long, 29 amino acids long, 30 amino acids long, 31 amino acids long, 32 amino acids long, 33 amino acids long, 34 amino acids long, 35 amino acids long, 36 amino acids long, 37 amino acids long, 38 amino acids long, 39 amino acids long, 40 amino acids long, 41 amino acids long, 42 amino acids long, 43 amino acids long, 44 amino acids long, 45 amino acids long, 46 amino acids long, 47 amino acids long, 48 amino acids long, 49 amino acids, or 50 amino acids long.
[0096] In some embodiments, the fourth peptide comprises SEQ ID NO:28. In some embodiments, the fourth peptide comprising SEQ ID NO:28 is SEQ ID NO:32. In some embodiments, the fourth peptide comprising SEQ ID NO:28 or a variant thereof is a variant of SEQ ID NO:32, where at least one amino acid of the sequence of SEQ ID NO:32 is substituted, deleted, inserted, and / or added relative to the first peptide. In some embodiments, the fourth peptide comprising SEQ ID NO:28 or a variant thereof is a variant of SEQ ID NO:32, where one, two, three, four, or five amino acids of SEQ ID NO:32 are deleted, substituted, inserted, and / or added relative to the first peptide, and where there is a substitution, insertion, and / or addition, a moiety is substituted, inserted, and / or added relative to the sequence. In some embodiments, the substituted, inserted, or added moiety is a natural amino acid (e.g., an α-amino acid or an L-amino acid or a D-amino acid) or an unnatural amino acid. In some embodiments, the substituted, inserted or added moiety is an amino acid substitution or a linker.
[0097] In some embodiments, the fourth peptide comprising SEQ ID NO:28 or a variant thereof is substantially homologous to a portion of labyrinthin (SEQ ID NO:1). In some embodiments, the fourth peptide comprising SEQ ID NO:28 or a variant thereof has at least about 60% sequence similarity to a portion of labyrinthin (SEQ ID NO:1), such as at least about 65%, 70%, 75%, 80%, 85%, 90%, or 95% similarity. In some embodiments, a variant of SEQ ID NO:32 has at least about 60% sequence similarity to a portion of labyrinthin (SEQ ID NO:1), such as at least about 65%, 70%, 75%, 80%, 85%, 90%, or 95% similarity.
[0098] In some embodiments, for any of the antigenic compositions disclosed herein, one or more of the labyrinthin-derived peptides are soluble in solution. In some embodiments, one or more of the labyrinthin-derived peptides have a solubility in solution of at least about 0.1 mg / mL, e.g., at least about 0.5 mg / mL, 1 mg / ml, 2 mg / ml, 3 mg / ml, 4 mg / ml, 5 mg / ml, 6 mg / ml, 7 mg / ml, 8 mg / ml, 9 mg / ml, or 10 mg / ml. In some embodiments, the solution is a pharma- ceutically acceptable vehicle. In some embodiments, the solution comprises one or more of water, a buffer such as PBS, and a salt solution such as a sodium chloride solution.
[0099] In some embodiments, for any of the antigenic compositions disclosed herein, each of the one or more Labyrinthin-derived peptides has a purity of at least about 90%, e.g., at least about any of 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%. Methods for determining peptide purity are known in the art, such as using high performance liquid chromatography techniques.
[0100] In some embodiments, for any of the antigenic compositions disclosed herein, one or more of the Labyrinthin-derived peptides therein activate both T cell and / or B cell adaptive immune responses. In some embodiments, for any of the antigenic compositions disclosed herein, each Labyrinthin-derived peptide activates T cell and B cell adaptive immune responses. In some embodiments, activation of the T cell adaptive immune response results in the production of target-specific receptors, e.g., anti-Labyrinthin-derived peptide epitope T cell receptors. In some embodiments, activation of the T cell adaptive immune response is mediated through class I major histocompatibility complex (MHC I). In some embodiments, activation of the T cell adaptive immune response is mediated through class II major histocompatibility complex (MHC II). In some embodiments, activation of the T cell adaptive immune response is mediated through MHC I and MHC II. In some embodiments, activation of the B cell adaptive immune response results in the production of target-specific immunoglobulins, e.g., anti-Labyrinthin-derived peptide epitope antibodies. Labyrinthin-derived peptide activation of T-cell and B-cell adaptive immune responses and methods for assessing whether a peptide is a T-cell and / or B-cell epitope are known in the art, see, for example, Bercovici, N. et al., Clin Diagn Lab Immunol, 2000, 7, 859-864; and McAllister, EJ et al., J Immunol, 2017, 199, 2998-3003.
[0101] In some embodiments, for any of the antigenic compositions disclosed herein, at least one of the one or more labyrinthin-derived peptides of the antigenic composition is conjugated. In some embodiments, the labyrinthin-derived peptide is conjugated to a carrier molecule. In some embodiments, the labyrinthin-derived peptide is conjugated to a protein such as ovalbumin, albumin, keyhole limpet hemocyanin (KLH), diphtheria toxoid, tetanus toxoid, or CRM197. In some embodiments, the labyrinthin-derived peptide is conjugated to a lipid. In some embodiments, the labyrinthin-derived peptide is conjugated to an adjuvant. In some embodiments, the labyrinthin-derived peptide is conjugated to an immunologically effective (e.g., immune enhancing) adjuvant. In some embodiments, the labyrinthin-derived peptide is conjugated to one or more other labyrinthin-derived peptides. In some embodiments, the labyrinthin-derived peptide is conjugated to one or more other labyrinthin-derived peptides, where the resulting sequence of the peptide is not the sequence of labyrinthin or a portion thereof (SEQ ID NO:1). For example, in some embodiments, a first labyrinthin-derived peptide is conjugated to a second labyrinthin-derived peptide, where the resulting sequence of the first and second peptides is not the sequence of labyrinthin or a portion thereof (SEQ ID NO:1). In some embodiments, the labyrinthin-derived peptide is conjugated via a linker, such as a cross-linker. In some embodiments, the labyrinthin-derived peptide is conjugated to a linker.
[0102] In some embodiments, the antigenic composition comprises one or more labyrinthin-derived peptides selected from the group comprising: (a) a first peptide comprising SEQ ID NO:25 or a variant thereof; (b) a second peptide comprising SEQ ID NO:26 or a variant thereof; (c) a third peptide comprising SEQ ID NO:27 or a variant thereof; and (d) a fourth peptide comprising SEQ ID NO:28 or a variant thereof, wherein each peptide comprises a T cell epitope and a B cell epitope. For example, in some embodiments, the antigenic composition comprises a first peptide comprising SEQ ID NO:25 or a variant thereof, wherein the first peptide comprises a T cell epitope and a B cell epitope. In some embodiments, the one or more labyrinthin-derived peptides are 21 to 24 amino acids in length, e.g., 22 or 23 amino acids in length. In some embodiments, the first peptide comprising SEQ ID NO:25 or a variant thereof comprises SEQ ID NO:29 or a variant thereof. In some embodiments, the first peptide comprising SEQ ID NO:25 or a variant thereof has a sequence similarity of at least about 90% similarity, e.g., at least about 92% similarity, 95% similarity, or 97% similarity, to a portion of Labyrinthin (SEQ ID NO:1). In some embodiments, the first peptide comprising SEQ ID NO:25 is SEQ ID NO:29. In some embodiments, the first peptide comprising SEQ ID NO:25 or a variant thereof is conjugated. In some embodiments, the antigenic composition comprises a first peptide comprising SEQ ID NO:29 or a variant thereof, wherein the first peptide comprises a T cell epitope and a B cell epitope. In some embodiments, the antigenic composition comprises a first peptide, wherein the first peptide is SEQ ID NO:29, wherein the first peptide comprises a T cell epitope and a B cell epitope. In some embodiments, each peptide of the antigenic composition activates adaptive immune responses of T cells and B cells.
[0103] In some embodiments, the antigenic composition comprises one or more labyrinthin-derived peptides selected from the group consisting of: (a) a first peptide comprising SEQ ID NO:25 or a variant thereof; (b) a second peptide comprising SEQ ID NO:26 or a variant thereof; (c) a third peptide comprising SEQ ID NO:27 or a variant thereof; and (d) a fourth peptide comprising SEQ ID NO:28 or a variant thereof. In some embodiments, the antigenic composition comprises: (a) a first peptide comprising SEQ ID NO:25 or a variant thereof; (b) a second peptide comprising SEQ ID NO:26 or a variant thereof; (c) a third peptide comprising SEQ ID NO:27 or a variant thereof; and (d) a fourth peptide comprising SEQ ID NO:28 or a variant thereof. In some embodiments, the antigenic composition comprises (a) a first peptide comprising SEQ ID NO:25 or a variant thereof; (b) a second peptide comprising SEQ ID NO:26 or a variant thereof; (c) a third peptide comprising SEQ ID NO:27 or a variant thereof; and (d) a fourth peptide comprising SEQ ID NO:28 or a variant thereof, where only these four labyrinthin-derived peptides are present in the antigenic composition. In some embodiments, the labyrinthin-derived peptides are 21 to 24 amino acids in length, for example 22 or 23 amino acids in length. In some embodiments, the antigenic composition comprising a peptide comprising SEQ ID NO:25 or a variant thereof comprises SEQ ID NO:29 or a variant thereof. In some embodiments, the antigenic composition comprising a peptide comprising SEQ ID NO:26 or a variant thereof comprises SEQ ID NO:30 or a variant thereof. In some embodiments, the antigenic composition comprising a peptide comprising SEQ ID NO:27 or a variant thereof comprises SEQ ID NO:31 or a variant thereof. In some embodiments, the antigenic composition comprising a peptide comprising SEQ ID NO:28 or a variant thereof comprises SEQ ID NO:32 or a variant thereof. In some embodiments, the antigenic composition comprises (a) a first peptide comprising SEQ ID NO:29 or a variant thereof; (b) a second peptide comprising SEQ ID NO:30 or a variant thereof; (c) a third peptide comprising SEQ ID NO:31 or a variant thereof; and (d) a fourth peptide comprising SEQ ID NO:32 or a variant thereof, wherein the antigenic composition only comprises these four Labyrinthin-derived peptides.In some embodiments, the Labyrinthin-derived peptide comprises a T cell epitope and / or a B cell epitope.
[0104] In some embodiments, the antigenic composition comprises a second peptide comprising SEQ ID NO:26 or a variant thereof, wherein the second peptide comprises a T cell epitope and a B cell epitope. In some embodiments, the one or more labyrinthin-derived peptides are 21 to 24 amino acids in length, for example, 22 or 23 amino acids in length. In some embodiments, the second peptide comprising SEQ ID NO:26 or a variant thereof comprises SEQ ID NO:30 or a variant thereof. In some embodiments, the second peptide comprising SEQ ID NO:30 or a variant thereof has sequence similarity of at least about 90% similarity, for example, at least about 92% similarity, 95% similarity, or 97% similarity, to a portion of labyrinthin (SEQ ID NO:1). In some embodiments, the second peptide comprising SEQ ID NO:26 is SEQ ID NO:30. In some embodiments, the second peptide comprising SEQ ID NO:26 or a variant thereof is conjugated. In some embodiments, the antigenic composition comprises a second peptide comprising SEQ ID NO:30 or a variant thereof, wherein the second peptide comprises a T cell epitope and a B cell epitope. In some embodiments, the antigenic composition comprises a second peptide, wherein the second peptide is SEQ ID NO:30 and the second peptide comprises a T cell epitope and a B cell epitope. In some embodiments, each peptide of the antigenic composition activates a T cell and a B cell adaptive immune response.
[0105] In some embodiments, the antigenic composition comprises a third peptide comprising SEQ ID NO:27 or a variant thereof, wherein the third peptide comprises a T cell epitope and a B cell epitope. In some embodiments, the one or more labyrinthin-derived peptides are 21 to 24 amino acids in length, for example, 22 or 23 amino acids in length. In some embodiments, the third peptide comprising SEQ ID NO:27 or a variant thereof comprises SEQ ID NO:31 or a variant thereof. In some embodiments, the third peptide comprising SEQ ID NO:27 or a variant thereof has sequence similarity of at least about 90% similarity, for example, at least about 92% similarity, 95% similarity, or 97% similarity, to a portion of labyrinthin (SEQ ID NO:1). In some embodiments, the third peptide comprising SEQ ID NO:27 is SEQ ID NO:31. In some embodiments, the third peptide comprising SEQ ID NO:27 or a variant thereof is conjugated. In some embodiments, the antigenic composition comprises a third peptide comprising SEQ ID NO:31 or a variant thereof, wherein the third peptide comprises a T cell epitope and a B cell epitope. In some embodiments, the antigenic composition comprises a third peptide, wherein the third peptide is SEQ ID NO:31 and the third peptide comprises a T cell epitope and a B cell epitope.
[0106] In some embodiments, the antigenic composition comprises a fourth peptide comprising SEQ ID NO:28 or a variant thereof, wherein the fourth peptide comprises a T cell epitope and a B cell epitope. In some embodiments, the one or more labyrinthin-derived peptides are 21 to 24 amino acids in length, for example 22 or 23 amino acids in length. In some embodiments, the fourth peptide comprising SEQ ID NO:28 or a variant thereof comprises SEQ ID NO:32 or a variant thereof. In some embodiments, the fourth peptide comprising SEQ ID NO:28 or a variant thereof has sequence similarity of at least about 90% similarity, for example at least about 92% similarity, 95% similarity, or 97% similarity, to a portion of labyrinthin (SEQ ID NO:1). In some embodiments, the fourth peptide comprising SEQ ID NO:28 is SEQ ID NO:32. In some embodiments, the fourth peptide comprising SEQ ID NO:28 or a variant thereof is conjugated. In some embodiments, the antigenic composition comprises a fourth peptide comprising SEQ ID NO:32 or a variant thereof, wherein the fourth peptide comprises a T cell epitope and a B cell epitope. In some embodiments, the antigenic composition comprises a fourth peptide, wherein the fourth peptide is SEQ ID NO:32 and the fourth peptide comprises a T cell epitope and a B cell epitope. In some embodiments, each peptide of the antigenic composition activates a T cell and a B cell adaptive immune response.
[0107] In some embodiments, the antigenic composition comprises two or more labyrinthin-derived peptides. For example, in some embodiments, the antigenic composition comprises (a) a first peptide comprising SEQ ID NO:25 or a variant thereof; and (b) a second peptide comprising SEQ ID NO:26 or a variant thereof, where each peptide comprises a T cell epitope and a B cell epitope. In some embodiments, each of the two or more labyrinthin-derived peptides is 21 to 24 amino acids in length, e.g., 22 or 23 amino acids in length. In some embodiments, the first peptide comprising SEQ ID NO:25 or a variant thereof comprises SEQ ID NO:29 or a variant thereof. In some embodiments, the first peptide comprising SEQ ID NO:25 or a variant thereof has sequence similarity of at least about 90% similarity, e.g., at least about 92% similarity, 95% similarity, or 97% similarity, to a portion of labyrinthin (SEQ ID NO:1). In some embodiments, the first peptide comprising SEQ ID NO:25 is SEQ ID NO:29. In some embodiments, the first peptide comprising SEQ ID NO:25 or a variant thereof is conjugated. In some embodiments, the second peptide comprising SEQ ID NO:26 or a variant thereof comprises SEQ ID NO:30 or a variant thereof. In some embodiments, the second peptide comprising SEQ ID NO:30 or a variant thereof has a sequence similarity of at least about 90% similarity, for example at least about 92% similarity, 95% similarity, or 97% similarity, to a portion of Labyrinthin (SEQ ID NO:1). In some embodiments, the second peptide comprising SEQ ID NO:26 is SEQ ID NO:30. In some embodiments, the second peptide comprising SEQ ID NO:26 or a variant thereof is conjugated. In some embodiments, the antigenic composition comprises (a) a first peptide comprising SEQ ID NO:29 or a variant thereof; and (b) a second peptide comprising SEQ ID NO:30 or a variant thereof, wherein each peptide comprises a T cell epitope and a B cell epitope.In some embodiments, the antigenic composition comprises (a) a first peptide, the first peptide being SEQ ID NO: 29; and (b) a second peptide, the second peptide being SEQ ID NO: 30, wherein each peptide comprises a T cell epitope and a B cell epitope. In some embodiments, each peptide of the antigenic composition activates T cell and B cell adaptive immune responses.
[0108] In some embodiments, the antigenic composition comprises (a) a first peptide comprising SEQ ID NO:25 or a variant thereof; and (b) a third peptide comprising SEQ ID NO:27 or a variant thereof, where each peptide comprises a T cell epitope and a B cell epitope. In some embodiments, each of the two or more labyrinthin-derived peptides is 21 to 24 amino acids in length, for example, 22 or 23 amino acids in length. In some embodiments, the first peptide comprising SEQ ID NO:25 or a variant thereof comprises SEQ ID NO:29 or a variant thereof. In some embodiments, the first peptide comprising SEQ ID NO:25 or a variant thereof has sequence similarity of at least about 90% similarity, for example, at least about 92% similarity, 95% similarity, or 97% similarity, to a portion of labyrinthin (SEQ ID NO:1). In some embodiments, the first peptide comprising SEQ ID NO:25 is SEQ ID NO:29. In some embodiments, the first peptide comprising SEQ ID NO:25 or a variant thereof is conjugated. In some embodiments, the third peptide comprising SEQ ID NO:27 or a variant thereof comprises SEQ ID NO:31 or a variant thereof. In some embodiments, the third peptide comprising SEQ ID NO:27 or a variant thereof has a sequence similarity of at least about 90% similarity, e.g., at least about 92% similarity, 95% similarity, or 97% similarity, to a portion of Labyrinthin (SEQ ID NO:1). In some embodiments, the third peptide comprising SEQ ID NO:27 is SEQ ID NO:31. In some embodiments, the third peptide comprising SEQ ID NO:27 or a variant thereof is conjugated. In some embodiments, the antigenic composition comprises (a) a first peptide comprising SEQ ID NO:29 or a variant thereof; and (b) a third peptide comprising SEQ ID NO:31 or a variant thereof, wherein each peptide comprises a T cell epitope and a B cell epitope. In some embodiments, the antigenic composition comprises (a) a first peptide, the first peptide being SEQ ID NO:29; and (b) a third peptide, the third peptide being SEQ ID NO:31, wherein each peptide comprises a T cell epitope and a B cell epitope.
[0109] In some embodiments, the antigenic composition comprises: (a) a first peptide comprising SEQ ID NO:25 or a variant thereof; and (b) a fourth peptide comprising SEQ ID NO:28 or a variant thereof, where each peptide comprises a T cell epitope and a B cell epitope. In some embodiments, the two or more labyrinthin-derived peptides are 21 to 24 amino acids in length, for example, 22 or 23 amino acids in length. In some embodiments, the first peptide comprising SEQ ID NO:25 or a variant thereof comprises SEQ ID NO:29 or a variant thereof. In some embodiments, the first peptide comprising SEQ ID NO:25 or a variant thereof has sequence similarity of at least about 90% similarity, for example, at least about 92% similarity, 95% similarity, or 97% similarity, to a portion of labyrinthin (SEQ ID NO:1). In some embodiments, the first peptide comprising SEQ ID NO:25 is SEQ ID NO:29. In some embodiments, the first peptide comprising SEQ ID NO:25 or a variant thereof is conjugated. In some embodiments, the fourth peptide comprising SEQ ID NO:28 or a variant thereof comprises SEQ ID NO:32 or a variant thereof. In some embodiments, the fourth peptide comprising SEQ ID NO:28 or a variant thereof has a sequence similarity of at least about 90% similarity, e.g., at least about 92% similarity, 95% similarity, or 97% similarity, to a portion of Labyrinthin (SEQ ID NO:1). In some embodiments, the fourth peptide comprising SEQ ID NO:28 is SEQ ID NO:32. In some embodiments, the fourth peptide comprising SEQ ID NO:28 or a variant thereof is conjugated. In some embodiments, the antigenic composition comprises (a) a first peptide comprising SEQ ID NO:29 or a variant thereof; and (b) a fourth peptide comprising SEQ ID NO:32 or a variant thereof, wherein each peptide comprises a T cell epitope and a B cell epitope. In some embodiments, the antigenic composition comprises (a) a first peptide, the first peptide being SEQ ID NO:29; and (b) a fourth peptide, the fourth peptide being SEQ ID NO:32, wherein each peptide comprises a T cell epitope and a B cell epitope.
[0110] In some embodiments, the antigenic composition comprises (a) a second peptide comprising SEQ ID NO:26 or a variant thereof; and (b) a third peptide comprising SEQ ID NO:27 or a variant thereof, where each peptide comprises a T cell epitope and a B cell epitope. In some embodiments, the two or more labyrinthin-derived peptides are 21 to 24 amino acids in length, for example, 22 or 23 amino acids in length. In some embodiments, the second peptide comprising SEQ ID NO:26 or a variant thereof comprises SEQ ID NO:30 or a variant thereof. In some embodiments, the second peptide comprising SEQ ID NO:30 or a variant thereof has sequence similarity of at least about 90% similarity, for example, at least about 92% similarity, 95% similarity, or 97% similarity, to a portion of labyrinthin (SEQ ID NO:1). In some embodiments, the second peptide comprising SEQ ID NO:26 is SEQ ID NO:30. In some embodiments, the second peptide comprising SEQ ID NO:26 or a variant thereof is conjugated. In some embodiments, the third peptide comprising SEQ ID NO:27 or a variant thereof comprises SEQ ID NO:31 or a variant thereof. In some embodiments, the third peptide comprising SEQ ID NO:27 or a variant thereof has a sequence similarity of at least about 90% similarity, e.g., at least about 92% similarity, 95% similarity, or 97% similarity, to a portion of Labyrinthin (SEQ ID NO:1). In some embodiments, the third peptide comprising SEQ ID NO:27 is SEQ ID NO:31. In some embodiments, the third peptide comprising SEQ ID NO:27 or a variant thereof is conjugated. In some embodiments, the antigenic composition comprises (a) a second peptide comprising SEQ ID NO:30 or a variant thereof; and (b) a third peptide comprising SEQ ID NO:31 or a variant thereof, wherein each peptide comprises a T cell epitope and a B cell epitope. In some embodiments, the antigenic composition comprises (a) a second peptide, the second peptide being SEQ ID NO:30; and (b) a third peptide, the third peptide being SEQ ID NO:31, wherein each peptide comprises a T cell epitope and a B cell epitope.
[0111] In some embodiments, the antigenic composition comprises (a) a second peptide comprising SEQ ID NO:25 or a variant thereof; and (b) a fourth peptide comprising SEQ ID NO:28 or a variant thereof, where each peptide comprises a T cell epitope and a B cell epitope. In some embodiments, the two or more labyrinthin-derived peptides are 21 to 24 amino acids in length, for example, 22 or 23 amino acids in length. In some embodiments, the second peptide comprising SEQ ID NO:26 or a variant thereof comprises SEQ ID NO:30 or a variant thereof. In some embodiments, the second peptide comprising SEQ ID NO:30 or a variant thereof has sequence similarity of at least about 90% similarity, for example, at least about 92% similarity, 95% similarity, or 97% similarity, to a portion of labyrinthin (SEQ ID NO:1). In some embodiments, the second peptide comprising SEQ ID NO:26 is SEQ ID NO:30. In some embodiments, the second peptide comprising SEQ ID NO:26 or a variant thereof is conjugated. In some embodiments, the fourth peptide comprising SEQ ID NO:28 or a variant thereof comprises SEQ ID NO:32 or a variant thereof. In some embodiments, the fourth peptide comprising SEQ ID NO:28 or a variant thereof has a sequence similarity of at least about 90% similarity, e.g., at least about 92% similarity, 95% similarity, or 97% similarity, to a portion of Labyrinthin (SEQ ID NO:1). In some embodiments, the fourth peptide comprising SEQ ID NO:28 is SEQ ID NO:32. In some embodiments, the fourth peptide comprising SEQ ID NO:28 or a variant thereof is conjugated. In some embodiments, the antigenic composition comprises (a) a second peptide comprising SEQ ID NO:30 or a variant thereof; and (b) a fourth peptide comprising SEQ ID NO:32 or a variant thereof, wherein each peptide comprises a T cell epitope and a B cell epitope. In some embodiments, the antigenic composition comprises (a) a second peptide, the second peptide being SEQ ID NO:30; and (b) a fourth peptide, the fourth peptide being SEQ ID NO:32, wherein each peptide comprises a T cell epitope and a B cell epitope.
[0112] In some embodiments, the antigenic composition comprises: (a) a third peptide comprising SEQ ID NO:27 or a variant thereof; and (b) a fourth peptide comprising SEQ ID NO:28 or a variant thereof, where each peptide comprises a T cell epitope and a B cell epitope. In some embodiments, the two or more labyrinthin-derived peptides are 21 to 24 amino acids in length, for example, 22 or 23 amino acids in length. In some embodiments, the third peptide comprising SEQ ID NO:27 or a variant thereof comprises SEQ ID NO:31 or a variant thereof. In some embodiments, the third peptide comprising SEQ ID NO:27 or a variant thereof has sequence similarity of at least about 90% similarity, for example, at least about 92% similarity, 95% similarity, or 97% similarity, to a portion of labyrinthin (SEQ ID NO:1). In some embodiments, the third peptide comprising SEQ ID NO:27 is SEQ ID NO:31. In some embodiments, the third peptide comprising SEQ ID NO:27 or a variant thereof is conjugated. In some embodiments, the fourth peptide comprising SEQ ID NO:28 or a variant thereof comprises SEQ ID NO:32 or a variant thereof. In some embodiments, the fourth peptide comprising SEQ ID NO:28 or a variant thereof has a sequence similarity of at least about 90% similarity, e.g., at least about 92% similarity, 95% similarity, or 97% similarity, to a portion of Labyrinthin (SEQ ID NO:1). In some embodiments, the fourth peptide comprising SEQ ID NO:28 is SEQ ID NO:32. In some embodiments, the fourth peptide comprising SEQ ID NO:28 or a variant thereof is conjugated. In some embodiments, the antigenic composition comprises (a) a third peptide comprising SEQ ID NO:31 or a variant thereof; and (b) a fourth peptide comprising SEQ ID NO:32 or a variant thereof, wherein each peptide comprises a T cell epitope and a B cell epitope. In some embodiments, the antigenic composition comprises (a) a third peptide, the second peptide being SEQ ID NO:31; and (b) a fourth peptide, the fourth peptide being SEQ ID NO:32, wherein each peptide comprises a T cell epitope and a B cell epitope.
[0113] In some embodiments, the antigenic composition comprises three or more labyrinthin-derived peptides. For example, in some embodiments, the antigenic composition comprises (a) a first peptide comprising SEQ ID NO:25 or a variant thereof; (b) a second peptide comprising SEQ ID NO:26 or a variant thereof; and (c) a third peptide comprising SEQ ID NO:27 or a variant thereof, wherein each peptide comprises a T cell epitope and a B cell epitope. In some embodiments, each of the three or more labyrinthin-derived peptides is 21 to 24 amino acids in length, e.g., 22 or 23 amino acids in length. In some embodiments, the first peptide comprising SEQ ID NO:25 or a variant thereof comprises SEQ ID NO:29 or a variant thereof. In some embodiments, the first peptide comprising SEQ ID NO:25 or a variant thereof has a sequence similarity of at least about 90% similarity, e.g., at least about any of 92% similarity, 95% similarity, or 97% similarity, to a portion of labyrinthin (SEQ ID NO:1). In some embodiments, the first peptide comprising SEQ ID NO:25 is SEQ ID NO:29. In some embodiments, the first peptide comprising SEQ ID NO:25 or a variant thereof is conjugated. In some embodiments, the second peptide comprising SEQ ID NO:26 or a variant thereof comprises SEQ ID NO:30 or a variant thereof. In some embodiments, the second peptide comprising SEQ ID NO:30 or a variant thereof has a sequence similarity of at least about 90% similarity, for example at least about 92% similarity, 95% similarity, or 97% similarity, to a portion of Labyrinthin (SEQ ID NO:1). In some embodiments, the second peptide comprising SEQ ID NO:26 is SEQ ID NO:30. In some embodiments, the second peptide comprising SEQ ID NO:26 or a variant thereof is conjugated. In some embodiments, the third peptide comprising SEQ ID NO:27 or a variant thereof comprises SEQ ID NO:31 or a variant thereof. In some embodiments, the third peptide comprising SEQ ID NO:27 or a variant thereof has sequence similarity to a portion of Labyrinthin (SEQ ID NO:1) of at least about 90% similarity, e.g., at least about 92% similarity, at least about 95% similarity, or at least about 97% similarity.In some embodiments, the third peptide comprising SEQ ID NO:27 is SEQ ID NO:31. In some embodiments, the third peptide comprising SEQ ID NO:27 or a variant thereof is conjugated. In some embodiments, the antigenic composition comprises (a) a first peptide comprising SEQ ID NO:29 or a variant thereof; (b) a second peptide comprising SEQ ID NO:30 or a variant thereof; and (c) a third peptide comprising SEQ ID NO:31 or a variant thereof, wherein each peptide comprises a T cell epitope and a B cell epitope. In some embodiments, the antigenic composition comprises (a) a first peptide, the first peptide being SEQ ID NO:29; (b) a second peptide, the second peptide being SEQ ID NO:30; and (c) a third peptide, the third peptide being SEQ ID NO:31, wherein each peptide comprises a T cell epitope and a B cell epitope.
[0114] In some embodiments, the antigenic composition comprises (a) a first peptide comprising SEQ ID NO:25 or a variant thereof; (b) a second peptide comprising SEQ ID NO:26 or a variant thereof; and (c) a fourth peptide comprising SEQ ID NO:28 or a variant thereof, wherein each peptide comprises a T cell epitope and a B cell epitope. In some embodiments, each of the three or more labyrinthin-derived peptides is 21 to 24 amino acids in length, e.g., 22 or 23 amino acids in length. In some embodiments, the first peptide comprising SEQ ID NO:25 or a variant thereof comprises SEQ ID NO:29 or a variant thereof. In some embodiments, the first peptide comprising SEQ ID NO:25 or a variant thereof has sequence similarity of at least about 90% similarity, e.g., at least about 92% similarity, 95% similarity, or 97% similarity, to a portion of labyrinthin (SEQ ID NO:1). In some embodiments, the first peptide comprising SEQ ID NO:25 is SEQ ID NO:29. In some embodiments, the first peptide comprising SEQ ID NO:25 or a variant thereof is conjugated. In some embodiments, the second peptide comprising SEQ ID NO:26 or a variant thereof comprises SEQ ID NO:30 or a variant thereof. In some embodiments, the second peptide comprising SEQ ID NO:30 or a variant thereof has a sequence similarity of at least about 90% similarity, for example at least about 92% similarity, 95% similarity, or 97% similarity, to a portion of Labyrinthin (SEQ ID NO:1). In some embodiments, the second peptide comprising SEQ ID NO:26 is SEQ ID NO:30. In some embodiments, the second peptide comprising SEQ ID NO:26 or a variant thereof is conjugated. In some embodiments, the fourth peptide comprising SEQ ID NO:28 or a variant thereof comprises SEQ ID NO:32 or a variant thereof. In some embodiments, the fourth peptide comprising SEQ ID NO:28 or a variant thereof has sequence similarity of at least about 90% to a portion of Labyrinthin (SEQ ID NO:1), e.g., at least about 92% similarity, 95% similarity, or 97% similarity. In some embodiments, the fourth peptide comprising SEQ ID NO:28 is SEQ ID NO:32.In some embodiments, the fourth peptide comprising SEQ ID NO:28 or a variant thereof is conjugated. In some embodiments, the antigenic composition comprises (a) a first peptide comprising SEQ ID NO:29 or a variant thereof; (b) a second peptide comprising SEQ ID NO:30 or a variant thereof; and (c) a fourth peptide comprising SEQ ID NO:32 or a variant thereof, wherein each peptide comprises a T cell epitope and a B cell epitope. In some embodiments, the antigenic composition comprises (a) a first peptide, the first peptide being SEQ ID NO:29; (b) a second peptide, the second peptide being SEQ ID NO:30; and (c) a fourth peptide, the fourth peptide being SEQ ID NO:32, wherein each peptide comprises a T cell epitope and a B cell epitope.
[0115] In some embodiments, the antigenic composition comprises (a) a first peptide comprising SEQ ID NO:25 or a variant thereof; (b) a third peptide comprising SEQ ID NO:26 or a variant thereof; and (c) a fourth peptide comprising SEQ ID NO:28 or a variant thereof, wherein each peptide comprises a T cell epitope and a B cell epitope. In some embodiments, each of the three or more labyrinthin-derived peptides is 21 to 24 amino acids in length, e.g., 22 or 23 amino acids in length. In some embodiments, the first peptide comprising SEQ ID NO:25 or a variant thereof comprises SEQ ID NO:29 or a variant thereof. In some embodiments, the first peptide comprising SEQ ID NO:25 or a variant thereof has sequence similarity of at least about 90% similarity, e.g., at least about 92% similarity, 95% similarity, or 97% similarity, to a portion of labyrinthin (SEQ ID NO:1). In some embodiments, the first peptide comprising SEQ ID NO:25 is SEQ ID NO:29. In some embodiments, the first peptide comprising SEQ ID NO:25 or a variant thereof is conjugated. In some embodiments, the third peptide comprising SEQ ID NO:27 or a variant thereof comprises SEQ ID NO:31 or a variant thereof. In some embodiments, the third peptide comprising SEQ ID NO:27 or a variant thereof has a sequence similarity of at least about 90% similarity, for example at least about 92% similarity, 95% similarity, or 97% similarity, to a portion of Labyrinthin (SEQ ID NO:1). In some embodiments, the third peptide comprising SEQ ID NO:27 is SEQ ID NO:31. In some embodiments, the third peptide comprising SEQ ID NO:27 or a variant thereof is conjugated. In some embodiments, the fourth peptide comprising SEQ ID NO:28 or a variant thereof comprises SEQ ID NO:32 or a variant thereof. In some embodiments, the fourth peptide comprising SEQ ID NO:28 or a variant thereof has sequence similarity of at least about 90% to a portion of Labyrinthin (SEQ ID NO:1), e.g., at least about 92% similarity, 95% similarity, or 97% similarity. In some embodiments, the fourth peptide comprising SEQ ID NO:28 is SEQ ID NO:32.In some embodiments, the fourth peptide comprising SEQ ID NO:28 or a variant thereof is conjugated. In some embodiments, the antigenic composition comprises (a) a first peptide comprising SEQ ID NO:29 or a variant thereof; (b) a third peptide comprising SEQ ID NO:31 or a variant thereof; and (c) a fourth peptide comprising SEQ ID NO:32 or a variant thereof, wherein each peptide comprises a T cell epitope and a B cell epitope. In some embodiments, the antigenic composition comprises (a) a first peptide, the first peptide being SEQ ID NO:29; (b) a third peptide, the third peptide being SEQ ID NO:31; and (c) a fourth peptide, the fourth peptide being SEQ ID NO:32, wherein each peptide comprises a T cell epitope and a B cell epitope.
[0116] In some embodiments, the antigenic composition comprises (a) a second peptide comprising SEQ ID NO:26 or a variant thereof; (b) a third peptide comprising SEQ ID NO:27 or a variant thereof; and (c) a fourth peptide comprising SEQ ID NO:28 or a variant thereof, wherein each peptide comprises a T cell epitope and a B cell epitope. In some embodiments, each of the three or more labyrinthin-derived peptides is 21 to 24 amino acids in length, e.g., 22 or 23 amino acids in length. In some embodiments, the second peptide comprising SEQ ID NO:26 or a variant thereof comprises SEQ ID NO:30 or a variant thereof. In some embodiments, the second peptide comprising SEQ ID NO:30 or a variant thereof has sequence similarity of at least about 90% similarity, e.g., at least about 92% similarity, 95% similarity, or 97% similarity, to a portion of labyrinthin (SEQ ID NO:1). In some embodiments, the second peptide comprising SEQ ID NO:26 is SEQ ID NO:30. In some embodiments, the second peptide comprising SEQ ID NO:26 or a variant thereof is conjugated. In some embodiments, the third peptide comprising SEQ ID NO:27 or a variant thereof comprises SEQ ID NO:31 or a variant thereof. In some embodiments, the third peptide comprising SEQ ID NO:27 or a variant thereof has a sequence similarity of at least about 90% similarity, such as at least about 92% similarity, 95% similarity, or 97% similarity, to a portion of Labyrinthin (SEQ ID NO:1). In some embodiments, the third peptide comprising SEQ ID NO:27 is SEQ ID NO:31. In some embodiments, the third peptide comprising SEQ ID NO:27 or a variant thereof is conjugated. In some embodiments, the fourth peptide comprising SEQ ID NO:28 or a variant thereof comprises SEQ ID NO:32 or a variant thereof. In some embodiments, the fourth peptide comprising SEQ ID NO:28 or a variant thereof has sequence similarity of at least about 90% to a portion of Labyrinthin (SEQ ID NO:1), e.g., at least about 92% similarity, 95% similarity, or 97% similarity. In some embodiments, the fourth peptide comprising SEQ ID NO:28 is SEQ ID NO:32.In some embodiments, the fourth peptide comprising SEQ ID NO:28 or a variant thereof is conjugated. In some embodiments, the antigenic composition comprises (a) a second peptide comprising SEQ ID NO:30 or a variant thereof; (b) a third peptide comprising SEQ ID NO:31 or a variant thereof; and (c) a fourth peptide comprising SEQ ID NO:32 or a variant thereof, wherein each peptide comprises a T cell epitope and a B cell epitope. In some embodiments, the antigenic composition comprises (a) a second peptide, the second peptide being SEQ ID NO:30; (b) a third peptide, the third peptide being SEQ ID NO:31; and (c) a fourth peptide, the fourth peptide being SEQ ID NO:32, wherein each peptide comprises a T cell epitope and a B cell epitope.
[0117] In some embodiments, the antigenic composition comprises four or more labyrinthin-derived peptides. For example, in some embodiments, the antigenic composition comprises (a) a first peptide comprising SEQ ID NO:25 or a variant thereof; (b) a second peptide comprising SEQ ID NO:26 or a variant thereof; (c) a third peptide comprising SEQ ID NO:27 or a variant thereof; and (d) a fourth peptide comprising SEQ ID NO:28 or a variant thereof, wherein each peptide comprises a T cell epitope and a B cell epitope. In some embodiments, each of the four or more labyrinthin-derived peptides is 21 to 24 amino acids in length, e.g., 22 or 23 amino acids in length. In some embodiments, the first peptide comprising SEQ ID NO:25 or a variant thereof comprises SEQ ID NO:29 or a variant thereof. In some embodiments, the first peptide comprising SEQ ID NO:25 or a variant thereof has at least about 90% sequence similarity, e.g., at least about 92% sequence similarity, 95% sequence similarity, or 97% sequence similarity, to a portion of labyrinthin (SEQ ID NO:1). In some embodiments, the first peptide comprising SEQ ID NO:25 is SEQ ID NO:29. In some embodiments, the first peptide comprising SEQ ID NO:25 or a variant thereof is conjugated. In some embodiments, the second peptide comprising SEQ ID NO:26 or a variant thereof comprises SEQ ID NO:30 or a variant thereof. In some embodiments, the second peptide comprising SEQ ID NO:30 or a variant thereof has at least about 90% sequence similarity, e.g., at least about 92% sequence similarity, 95% sequence similarity, or 97% sequence similarity, to a portion of labyrinthin (SEQ ID NO:1). In some embodiments, the second peptide comprising SEQ ID NO:26 is SEQ ID NO:30. In some embodiments, the second peptide comprises SEQ ID NO:26 or a variant thereof, and the third peptide comprises SEQ ID NO:31 or a variant thereof.In some embodiments, the third peptide comprising SEQ ID NO:27 or a variant thereof has a sequence similarity of at least about 90% to a portion of labyrinthin (SEQ ID NO:1), e.g., at least about 92% similarity, 95% similarity, or 97% similarity. In some embodiments, the third peptide comprising SEQ ID NO:27 is SEQ ID NO:31. In some embodiments, the third peptide comprising SEQ ID NO:27 or a variant thereof is conjugated. In some embodiments, the fourth peptide comprising SEQ ID NO:28 or a variant thereof comprises SEQ ID NO:32 or a variant thereof. In some embodiments, the fourth peptide comprising SEQ ID NO:28 or a variant thereof has a sequence similarity of at least about 90% to a portion of labyrinthin (SEQ ID NO:1), e.g., at least about 92% similarity, 95% similarity, or 97% similarity. In some embodiments, the fourth peptide comprising SEQ ID NO:28 is SEQ ID NO:32. In some embodiments, the fourth peptide comprising SEQ ID NO:28 or a variant thereof is conjugated. In some embodiments, the antigenic composition comprises (a) a first peptide comprising SEQ ID NO:29 or a variant thereof; (b) a second peptide comprising SEQ ID NO:30 or a variant thereof; (c) a third peptide comprising SEQ ID NO:31 or a variant thereof; and (d) a fourth peptide comprising SEQ ID NO:32 or a variant thereof, wherein each peptide comprises a T cell epitope and a B cell epitope. In some embodiments, the antigenic composition comprises (a) a first peptide, the first peptide being SEQ ID NO:29; (b) a second peptide, the second peptide being SEQ ID NO:30; (c) a third peptide, the third peptide being SEQ ID NO:31; and (d) a fourth peptide, the fourth peptide being SEQ ID NO:32, wherein each peptide comprises a T cell epitope and a B cell epitope.
[0118] In some embodiments where the antigenic composition comprises more than one labyrinthin-derived peptide, the ratio between each of the more than one labyrinthin-derived peptides can be selected to achieve a desired immunotherapeutic response. In some embodiments, more than one labyrinthin-derived peptide, such as two, three, or four labyrinthin-derived peptides, are all provided in about the same amount in the antigenic composition. For example, in some embodiments where the antigenic composition comprises more than one labyrinthin-derived peptide, the ratio of the first peptide to the second peptide is about 1:10 to about 10:1, such as about 1:9, 1:8, 1:7, 1:6, 1:5, 1:4, 1:3, 1:2, 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, or 9:1. In some embodiments, the antigenic composition comprises (a) a first peptide, the first peptide being SEQ ID NO:29; (b) a second peptide, the second peptide being SEQ ID NO:30; (c) a third peptide, the third peptide being SEQ ID NO:31; and (d) a fourth peptide, the fourth peptide being SEQ ID NO:32, wherein the ratio of the first peptide to the second peptide to the third peptide to the fourth peptide is about 1:1:1:1. In some embodiments, the antigenic composition comprises only the following peptides: (a) a first peptide, the first peptide being SEQ ID NO:29; (b) a second peptide, the second peptide being SEQ ID NO:30; (c) a third peptide, the third peptide being SEQ ID NO:31; and (d) a fourth peptide, the fourth peptide being SEQ ID NO:32, wherein the ratio of the first peptide to the second peptide to the third peptide to the fourth peptide is about 1:1:1:1.
[0119] In some embodiments, the antigenic composition comprises one or more labyrinthin-derived peptides, wherein each of the one or more labyrinthin-derived peptides has a pI of about 3.4 to about 3.1, such as about 3.3 to about 3.15. In some embodiments, the antigenic composition comprises one or more labyrinthin-derived peptides, wherein each of the one or more labyrinthin-derived peptides has a pI of less than about 3.4, such as less than about 3.35, 3.3, 3.25, 3.2, 3.15, 3.1, 3.05, or 3. In some embodiments, the antigenic composition comprises one or more labyrinthin-derived peptides, wherein each of the one or more labyrinthin-derived peptides has a pI of about 3.4, about 3.35, about 3.3, about 3.25, about 3.2, about 3.15, about 3.1, about 3.05, or about 3.
[0120] [Nucleic acid composition containing Labyrinthin-derived peptide] In some embodiments, a nucleic acid composition is provided that comprises one or more nucleic acids encoding at least one of the one or more labyrinthin-derived peptides comprised in the antigenic composition disclosed herein. In some embodiments, the nucleic acid composition comprises nucleic acids encoding at least two or more labyrinthin-derived peptides. In some embodiments, the nucleic acid composition comprises nucleic acids encoding at least three or more labyrinthin-derived peptides. In some embodiments, the nucleic acid composition comprises nucleic acids encoding four labyrinthin-derived peptides.
[0121] In some embodiments, the nucleic acid composition comprises one or more nucleic acids encoding a first peptide comprising SEQ ID NO:25 or a variant thereof. In some embodiments, the nucleic acid composition comprises one or more nucleic acids encoding a first peptide comprising SEQ ID NO:25. In some embodiments, the nucleic acid composition comprises one or more nucleic acids encoding a first peptide comprising SEQ ID NO:29 or a variant thereof. In some embodiments, the nucleic acid composition comprises one or more nucleic acids encoding a first peptide, wherein the first peptide is SEQ ID NO:29.
[0122] In some embodiments, the nucleic acid composition comprises one or more nucleic acids encoding a second peptide comprising SEQ ID NO:26 or a variant thereof. In some embodiments, the nucleic acid composition comprises one or more nucleic acids encoding a second peptide comprising SEQ ID NO:26. In some embodiments, the nucleic acid composition comprises one or more nucleic acids encoding a second peptide comprising SEQ ID NO:30 or a variant thereof. In some embodiments, the nucleic acid composition comprises one or more nucleic acids encoding a second peptide, where the second peptide is SEQ ID NO:30.
[0123] In some embodiments, the nucleic acid composition comprises one or more nucleic acids encoding a third peptide comprising SEQ ID NO:27 or a variant thereof. In some embodiments, the nucleic acid composition comprises one or more nucleic acids encoding a third peptide comprising SEQ ID NO:27. In some embodiments, the nucleic acid composition comprises one or more nucleic acids encoding a third peptide comprising SEQ ID NO:31 or a variant thereof. In some embodiments, the nucleic acid composition comprises one or more nucleic acids encoding a third peptide, where the third peptide is SEQ ID NO:31.
[0124] In some embodiments, the nucleic acid composition comprises one or more nucleic acids encoding a fourth peptide comprising SEQ ID NO:28 or a variant thereof. In some embodiments, the nucleic acid composition comprises one or more nucleic acids encoding a fourth peptide comprising SEQ ID NO:28. In some embodiments, the nucleic acid composition comprises one or more nucleic acids encoding a fourth peptide comprising SEQ ID NO:32 or a variant thereof. In some embodiments, the nucleic acid composition comprises one or more nucleic acids encoding a fourth peptide, where the fourth peptide is SEQ ID NO:32.
[0125] In some embodiments, the nucleic acid composition comprises one or more nucleic acids encoding at least one of the labyrinthin-derived peptides described herein, where at least one of the one or more nucleic acids is a sequence that is not naturally occurring. In some embodiments, the nucleic acid composition comprises one or more nucleic acids encoding at least one of the labyrinthin-derived peptides described herein, where at least one of the one or more nucleic acids is conjugated, such as conjugated to a label.
[0126] [Vaccine composition containing an antigenic composition] In some embodiments, a vaccine composition is provided that includes: (a) an effective amount of any one of the antigenic compositions described herein; and (b) a pharma- ceutically acceptable vehicle.
[0127] In some embodiments, the pharma- ceutically acceptable vehicle is one or more of an aqueous suspension, an oily suspension, an emulsion, a liposome, a virosome, and a nanoparticle. In some embodiments, the pharma- ceutically acceptable vehicle is selected from the group consisting of an aqueous suspension, an oily suspension, an emulsion such as an oil-in-water emulsion, a liposome, a virosome, and a nanoparticle. In some embodiments, the pharma- ceutically acceptable vehicle or a portion thereof stabilizes the antigenic composition or a portion thereof. In some embodiments, the pharma- ceutically acceptable vehicle or a portion thereof extends the circulating half-life of one or more labyrinthin-derived peptides compared to the circulating half-life of one or more labyrinthin-derived peptides administered without the pharma- ceutically acceptable vehicle.
[0128] In some embodiments, the pharma- ceutically acceptable vehicle comprises an additive. Additives are known in the art. See Mehmood, Y. et al., Open Science J Pharm Pharm Sci, 3, 2015, 19-27, which is incorporated herein by reference in its entirety. In some embodiments, the additive is one or more of a solvent, a cosolvent, a solubilizer, a wetting agent, a suspending agent, an emulsifier, a thickener, a chelating agent, an antioxidant, a reducing agent, an antimicrobial preservative, a buffer, a pH adjuster, a bulking agent, a protectant, and an isotonicity agent. In some embodiments, the additive comprises one or more of sugars, saccharides, sucrose, lactose, trehalose, mannitol, sorbitol, glucose, raffinose, amino acids, glycine, histidine, polyvinylpyrrolidone (PVP), sodium citrate, sodium chloride, potassium chloride, phosphate, monopotassium phosphate, disodium phosphate, Tris base-65, Tris acetate, Tris HCl-65, dextrose, dextran, ficoll, gelatin, starch, hydroxyethyl starch, magnesium stearate, polyethylene glycol (PEG), vitamins, and water.
[0129] In some embodiments, the pharma- ceutically acceptable vehicle comprises less than about 1% saline (NaCl), such as less than about 0.9%, 0.8%, 0.7%, 0.6%, 0.5%, 0.2%, 0.3%, 0.2%, or 0.1% saline. In some embodiments, the pharma- ceutically acceptable vehicle comprises less than about 1% saline, 0.9% saline, 0.8% saline, 0.7% saline, 0.6% saline, 0.5% saline, 0.2% saline, 0.3% saline, 0.2% saline, or 0.1% saline. In some embodiments, the vaccine composition comprises an effective amount of an antigenic composition described herein, wherein the antigenic composition is reconstituted in a pharma- ceutically acceptable vehicle comprising less than about 1% saline, e.g., less than about any of 0.9%, 0.8%, 0.7%, 0.6%, 0.5%, 0.2%, 0.3%, 0.2%, or 0.1% saline. In some embodiments, the vaccine composition comprises an effective amount of an antigenic composition described herein, wherein the antigenic composition is reconstituted in a pharma- ceutically acceptable vehicle comprising less than about 1% saline, saline, 0.9% saline, 0.8% saline, 0.7% saline, 0.6% saline, 0.5% saline, 0.2% saline, 0.3% saline, 0.2% saline, or 0.1% saline.
[0130] In some embodiments, the pharma- ceutically acceptable vehicle comprises one or more of a lipid, a lipopolysaccharide, a monophosphoryl lipid (A), a lipopolysaccharide, and 3-O-desacyl-4-monophosphoryl lipid A.
[0131] In some embodiments, the pharma- ceutically acceptable vehicle comprises an adjuvant. In some embodiments, the pharma- ceutically acceptable vehicle comprises an immune enhancing adjuvant. In some embodiments, the pharma- ceutical acceptable vehicle comprises an immune enhancing amount of an adjuvant, such as an immune enhancing adjuvant. Adjuvants, including immune enhancing adjuvants, are known in the art. In some embodiments, the adjuvant is granulocyte-macrophage colony stimulating factor (GM-CSF). In some embodiments, the adjuvant is GM-CSF of the organism to which the vaccine is intended to be administered, e.g., human GM-CSF. In some embodiments, the adjuvant comprises a saponin. See U.S. Patent Nos. 5,583,112, 5,057,540, 7,858,589, and 7,939,084; and Alving, CR et al., Curr Opin Immunol, 2012, 24, 310-315, which are incorporated herein by reference in their entireties. In some embodiments, the saponin is QS-21 (Quillaja saponaria Molina, fraction 21). In some embodiments, the adjuvant comprises 3-O-desacyl-4'-monophosphoryl lipid A (MPL). In some embodiments, the adjuvant comprises AS01B, which comprises QS-21, MPL, and liposomes comprising DOPC (dioleoylphosphatidylcholine) and cholesterol in a phosphate buffer. In some embodiments, the adjuvant comprises AS04. In some embodiments, the adjuvant comprises AS02A, hi some embodiments, the adjuvant comprises AS01E.
[0132] In some embodiments, the vaccine composition comprises any one of the antigenic compositions described herein, wherein the labyrinthin-derived peptide is in a salt form, including a pharma-ceutically acceptable salt. Pharmaceutically acceptable salts are known in the art. See Berge et al., J Pharm Sci, 66, 1977, 1-19, which is incorporated herein by reference in its entirety. In some embodiments, the pharma-ceutically acceptable salt is sodium chloride. In some embodiments, the pharma-ceutically acceptable salt is acetate. In some embodiments, the pharma-ceutically acceptable salt is sodium acetate. In some embodiments, the pharma-ceutically acceptable salt is potassium chloride.
[0133] In some embodiments, the pharma- ceutically acceptable vehicle comprises a pharma- ceutically acceptable acid. In some embodiments, the pharma- ceutically acceptable acid is acetic acid. In some embodiments, the concentration of the pharma- ceutically acceptable acid in the vaccine composition is about 1% or less, e.g., about 0.9%, 0.8%, 0.7%, 0.6%, 0.5%, 0.4%, 0.3%, 0.2%, or 0.1% or less.
[0134] In some embodiments where the vaccine composition comprises more than one labyrinthin-derived peptide, the ratio between each of the one or more labyrinthin-derived peptides can be selected to achieve a desired immunotherapeutic response. In some embodiments, more than one labyrinthin-derived peptide, such as two, three, or four labyrinthin-derived peptides, are all provided in about the same amount in the vaccine composition. For example, in some embodiments where the vaccine composition comprises more than one labyrinthin-derived peptide, the ratio of the first peptide to the second peptide is about 1:10 to about 10:1, such as about 1:9, 1:8, 1:7, 1:6, 1:5, 1:4, 1:3, 1:2, 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, or 9:1. In some embodiments where the vaccine composition comprises (a) a first peptide, the first peptide being SEQ ID NO:29; (b) a second peptide, the second peptide being SEQ ID NO:30; (c) a third peptide, the third peptide being SEQ ID NO:31; and (d) a fourth peptide, the fourth peptide being SEQ ID NO:32, the ratio of the first peptide to the second peptide to the third peptide to the fourth peptide is about 1:1:1:1. In some embodiments where the vaccine composition comprises only the following peptides: (a) a first peptide, the first peptide being SEQ ID NO:29; (b) a second peptide, the second peptide being SEQ ID NO:30; (c) a third peptide, the third peptide being SEQ ID NO:31; and (d) a fourth peptide, the fourth peptide being SEQ ID NO:32, the ratio of the first peptide to the second peptide to the third peptide to the fourth peptide is about 1:1:1:1.
[0135] In some embodiments, the vaccine composition comprises an effective amount of any one of the antigenic compositions described herein, where an effective amount is between about 1 μg and about 500 μg. In some embodiments, the vaccine composition comprises an effective amount of any one of the antigenic compositions described herein, where an effective amount is at least about 1 μg of total peptide, e.g., at least about 2 μg, 3 μg, 4 μg, 5 μg, 10 μg, 15 μg, 20 μg, 25 μg, 30 μg, 35 μg, 40 μg, 45 μg, 50 μg, 55 μg, 60 μg, 65 μg, g, 70 μg, 75 μg, 80 μg, 85 μg, 90 μg, 95 μg, 100 μg, 110 μg, 120 μg, 130 μg, 140 μg, 150 μg, 175 μg, 200 μg, 225 μg, 250 μg, 275 μg, 300 μg, 325 μg, 350 μg, 375 μg, 400 μg, 425 μg, 450 μg, 475 μg, or 500 μg.
[0136] In some embodiments, the vaccine composition comprises an effective amount of any one of the antigenic compositions described herein, where an effective amount is between about 1 μg and about 1000 μg. In some embodiments, the vaccine composition comprises an effective amount of any one of the antigenic compositions described herein, where an effective amount is at least about 1 μg of total peptide, e.g., at least about 2 μg, 3 μg, 4 μg, 5 μg, 10 μg, 15 μg, 20 μg, 25 μg, 30 μg, 35 μg, 40 μg, 45 μg, 50 μg, 55 μg, 60 μg, 65 μg, 70 μg, 75 μg, 80 μg, 85 μg, 90 μg, 95 μg, 100 μg, 110 μg, 120 μg, 130 μg, 140 μg. , 150 μg, 175 μg, 200 μg, 225 μg, 250 μg, 275 μg, 300 μg, 325 μg, 350 μg, 375 μg, 400 μg, 425 μg, 450 μg, 475 μg, 500 μg, 525 μg, 550 μg, 575 μg, 600 μg, 625 μg, 650 μg, 675 μg, 700 μg, 725 μg, 750 μg, 775 μg, 800 μg, 825 μg, 850 μg, 875 μg, 900 μg, 925 μg, 950 μg, 975 μg, or 1000 μg.
[0137] In some embodiments where the vaccine composition comprises more than one labyrinthin-derived peptide, each of the more than one labyrinthin-derived peptides is present in the vaccine composition in an amount of about 0.1 μg to about 500 μg. In some embodiments where the vaccine composition comprises more than one labyrinthin-derived peptide, each of the more than one labyrinthin-derived peptides is present in the vaccine composition in an amount of about 0.1 μg, 0.5 μg, 1 μg, 2 μg, 3 μg, 4 μg, 5 μg, 6 μg, 7 μg, 8 μg, 9 μg, 10 μg, 11 μg, 12 μg, 13 μg, 14 μg, 15 μg, 20 μg, 25 μg, 30 μg, 35 μg, 40 μg, 45 μg, 50 μg, 55 μg, The vaccine composition may be present in an amount of any of 60 μg, 65 μg, 70 μg, 75 μg, 80 μg, 85 μg, 90 μg, 95 μg, 100 μg, 110 μg, 120 μg, 130 μg, 140 μg, 150 μg, 175 μg, 200 μg, 225 μg, 250 μg, 275 μg, 300 μg, 325 μg, 350 μg, 375 μg, 400 μg, 425 μg, 450 μg, 475 μg, or 500 μg.
[0138] In some embodiments, the vaccine composition has a pH of about 5 to about 8.5, such as any of about 5 to about 7, about 6 to about 6.75, about 6.25 to about 6.75, about 6 to about 7, or about 6.5 to about 7.
[0139] In some embodiments, the vaccine composition has a pH of about any of 5, 5.25, 5.5, 5.75, 6, 6.25, 6.5, 6.75, 7, 7.25, 7.5, 7.75, 8, 8.25, or 8.5.
[0140] In some embodiments, the vaccine composition comprises another therapeutic agent, such as an immune checkpoint inhibitor.
[0141] In some embodiments, the vaccine composition is pharma- ceutically acceptable, hi some embodiments, the vaccine composition is pharma- ceutically sterile.
[0142] In some embodiments, the vaccine composition comprises (i) an effective amount of an antigenic composition described herein; and (ii) a pharma- ceutically acceptable vehicle. In some embodiments, the vaccine composition comprises (i) an effective amount of an antigenic composition described herein; and (ii) a pharma- ceutically acceptable vehicle comprising an adjuvant, such as GM-CSF. In some embodiments, the antigenic composition comprises one or more labyrinthin-derived peptides, wherein each labyrinthin-derived peptide comprises one or more T cell epitopes and B cell epitopes. In some embodiments, each of the one or more labyrinthin-derived peptides comprises a T cell epitope and a B cell epitope. In some embodiments, the one or more labyrinthin-derived peptides are 8 to 25 amino acids in length. In some embodiments, the one or more labyrinthin-derived peptides are substantially homologous to a portion of labyrinthin. In some embodiments, each of the one or more labyrinthin-derived peptides comprises a non-terminal proline residue.
[0143] In some embodiments, the vaccine composition comprises: (i) an effective amount of an antigenic composition comprising one or more labyrinthin-derived peptides selected from the group consisting of: (a) a first peptide comprising SEQ ID NO:25 or a variant thereof; (b) a second peptide comprising SEQ ID NO:26 or a variant thereof; (c) a third peptide comprising SEQ ID NO:27 or a variant thereof; and (d) a fourth peptide comprising SEQ ID NO:28 or a variant thereof, each peptide comprising a T cell epitope and a B cell epitope; and (ii) a pharmaceutically acceptable vehicle. For example, in some embodiments, the antigenic composition of the vaccine composition comprises a first peptide comprising SEQ ID NO:25 or a variant thereof, wherein the first peptide comprises a T cell epitope and a B cell epitope. In some embodiments, the second peptide is 21 to 24 amino acids in length, e.g., 22 or 23 amino acids in length. In some embodiments, the first peptide comprising SEQ ID NO:25 or a variant thereof comprises SEQ ID NO:29 or a variant thereof. In some embodiments, the first peptide comprising SEQ ID NO:25 or a variant thereof has a sequence similarity of at least about 90% similarity, e.g., at least about 92% similarity, 95% similarity, or 97% similarity, to a portion of Labyrinthin (SEQ ID NO:1). In some embodiments, the first peptide comprising SEQ ID NO:25 is SEQ ID NO:29. In some embodiments, the first peptide comprising SEQ ID NO:25 or a variant thereof is conjugated. In some embodiments, the antigenic composition comprises a first peptide comprising SEQ ID NO:29 or a variant thereof, wherein the first peptide comprises a T cell epitope and a B cell epitope. In some embodiments, the antigenic composition comprises a first peptide, wherein the first peptide is SEQ ID NO:29 and the first peptide comprises a T cell epitope and a B cell epitope. In some embodiments, each peptide of the antigenic composition activates adaptive immune responses of T cells and B cells. In some embodiments, the effective amount of the antigenic composition in the vaccine composition is from about 0.1 μg to about 1000 μg, such as from about 75 μg to about 150 μg, for example about 100 μg.In some embodiments, the effective amount of the antigenic composition of the vaccine composition is between about 25 μg and about 75 μg. In some embodiments, the pharma- ceutically acceptable vehicle comprises a saponin. In some embodiments, the vaccine composition comprises GM-CSF.
[0144] In some embodiments, the antigenic composition of the vaccine composition comprises a second peptide comprising SEQ ID NO:26 or a variant thereof, wherein the second peptide comprises a T cell epitope and a B cell epitope. In some embodiments, the second peptide is 21 to 24 amino acids in length, e.g., 22 or 23 amino acids in length. In some embodiments, the second peptide comprising SEQ ID NO:26 or a variant thereof comprises SEQ ID NO:30 or a variant thereof. In some embodiments, the second peptide comprising SEQ ID NO:30 or a variant thereof has sequence similarity of at least about 90% similarity, e.g., at least about 92% similarity, 95% similarity, or 97% similarity, to a portion of Labyrinthin (SEQ ID NO:1). In some embodiments, the second peptide comprising SEQ ID NO:26 is SEQ ID NO:30. In some embodiments, the second peptide comprising SEQ ID NO:26 or a variant thereof is conjugated. In some embodiments, the antigenic composition comprises a second peptide comprising SEQ ID NO:30 or a variant thereof, wherein the second peptide comprises a T cell epitope and a B cell epitope. In some embodiments, the antigenic composition comprises a second peptide, wherein the second peptide is SEQ ID NO:30 and the second peptide comprises a T cell epitope and a B cell epitope. In some embodiments, each peptide of the antigenic composition activates adaptive immune responses of T cells and B cells. In some embodiments, the effective amount of the antigenic composition in the vaccine composition is between about 0.1 μg and about 1000 μg, such as between about 75 μg and about 150 μg, such as about 100 μg. In some embodiments, the effective amount of the antigenic composition in the vaccine composition is between about 25 μg and about 75 μg. In some embodiments, the pharmaceutically acceptable vehicle comprises a saponin. In some embodiments, the vaccine composition comprises GM-CSF.
[0145] In some embodiments, the antigenic composition of the vaccine composition comprises a third peptide comprising SEQ ID NO:27 or a variant thereof, wherein the third peptide comprises a T cell epitope and a B cell epitope. In some embodiments, the third peptide is 21 to 24 amino acids in length, e.g., 22 or 23 amino acids in length. In some embodiments, the third peptide comprising SEQ ID NO:27 or a variant thereof comprises SEQ ID NO:31 or a variant thereof. In some embodiments, the third peptide comprising SEQ ID NO:27 or a variant thereof has sequence similarity of at least about 90% similarity, e.g., at least about 92% similarity, 95% similarity, or 97% similarity, to a portion of Labyrinthin (SEQ ID NO:1). In some embodiments, the third peptide comprising SEQ ID NO:27 is SEQ ID NO:31. In some embodiments, the third peptide comprising SEQ ID NO:27 or a variant thereof is conjugated. In some embodiments, the antigenic composition comprises a third peptide comprising SEQ ID NO:31 or a variant thereof, wherein the third peptide comprises a T cell epitope and a B cell epitope. In some embodiments, the antigenic composition comprises a third peptide, wherein the third peptide is SEQ ID NO:31 and the third peptide comprises a T cell epitope and a B cell epitope. In some embodiments, the effective amount of the antigenic composition in the vaccine composition is between about 0.1 μg and about 1000 μg, such as about 75 μg and about 150 μg, such as about 100 μg. In some embodiments, the effective amount of the antigenic composition in the vaccine composition is between about 25 μg and about 75 μg. In some embodiments, the pharma- ceutically acceptable vehicle comprises a saponin. In some embodiments, the vaccine composition comprises GM-CSF.
[0146] In some embodiments, the antigenic composition of the vaccine composition comprises a fourth peptide comprising SEQ ID NO:28 or a variant thereof, wherein the fourth peptide comprises a T cell epitope and a B cell epitope. In some embodiments, the fourth peptide is 21 to 24 amino acids in length, e.g., 22 or 23 amino acids in length. In some embodiments, the fourth peptide comprising SEQ ID NO:28 or a variant thereof comprises SEQ ID NO:32 or a variant thereof. In some embodiments, the fourth peptide comprising SEQ ID NO:28 or a variant thereof has a sequence similarity of at least about 90% similarity, e.g., at least about 92% similarity, 95% similarity, or 97% similarity, to a portion of labyrinthin (SEQ ID NO:1). In some embodiments, the fourth peptide comprising SEQ ID NO:28 is SEQ ID NO:32. In some embodiments, the fourth peptide comprising SEQ ID NO:28 or a variant thereof is conjugated. In some embodiments, the antigenic composition comprises a fourth peptide comprising SEQ ID NO:32 or a variant thereof, wherein the fourth peptide comprises a T cell epitope and a B cell epitope. In some embodiments, the antigenic composition comprises a fourth peptide, wherein the fourth peptide is SEQ ID NO:32 and the fourth peptide comprises a T cell epitope and a B cell epitope. In some embodiments, each peptide of the antigenic composition activates adaptive immune responses of T cells and B cells. In some embodiments, the effective amount of the antigenic composition in the vaccine composition is between about 0.1 μg and about 1000 μg, such as between about 75 μg and about 150 μg, such as about 100 μg. In some embodiments, the effective amount of the antigenic composition in the vaccine composition is between about 25 μg and about 75 μg. In some embodiments, the pharmaceutically acceptable vehicle comprises a saponin. In some embodiments, the vaccine composition comprises GM-CSF.
[0147] In some embodiments, the antigenic composition of the vaccine composition comprises two or more labyrinthin-derived peptides. For example, in some embodiments, the antigenic composition of the vaccine composition comprises (a) a first peptide comprising SEQ ID NO:25 or a variant thereof; and (b) a second peptide comprising SEQ ID NO:26 or a variant thereof, where each peptide comprises a T cell epitope and a B cell epitope. In some embodiments, each of the two or more labyrinthin-derived peptides is 21 to 24 amino acids in length, e.g., 22 or 23 amino acids in length. In some embodiments, the first peptide comprising SEQ ID NO:25 or a variant thereof comprises SEQ ID NO:29 or a variant thereof. In some embodiments, the first peptide comprising SEQ ID NO:25 or a variant thereof has a sequence similarity of at least about 90% similarity, e.g., at least about any of 92% similarity, 95% similarity, or 97% similarity, to a portion of labyrinthin (SEQ ID NO:1). In some embodiments, the first peptide comprising SEQ ID NO:25 is SEQ ID NO:29. In some embodiments, the first peptide comprising SEQ ID NO:25 or a variant thereof is conjugated. In some embodiments, the second peptide comprising SEQ ID NO:26 or a variant thereof comprises SEQ ID NO:30 or a variant thereof. In some embodiments, the second peptide comprising SEQ ID NO:30 or a variant thereof has sequence similarity of at least about 90% similarity, for example at least about 92% similarity, 95% similarity, or 97% similarity, to a portion of Labyrinthin (SEQ ID NO:1). In some embodiments, the second peptide comprising SEQ ID NO:26 is SEQ ID NO:30. In some embodiments, the second peptide comprising SEQ ID NO:26 or a variant thereof is conjugated. In some embodiments, the antigenic composition comprises: (a) a first peptide comprising SEQ ID NO:29 or a variant thereof; (b) a second peptide comprising SEQ ID NO:30 or a variant thereof, wherein each peptide comprises a T cell epitope and a B cell epitope.In some embodiments, the antigenic composition comprises (a) a first peptide, the first peptide being SEQ ID NO:29; (b) a second peptide, the second peptide being SEQ ID NO:30, wherein each peptide comprises a T cell epitope and a B cell epitope. In some embodiments, each peptide of the antigenic composition activates adaptive immune responses of T cells and B cells. In some embodiments, the effective amount of the antigenic composition in the vaccine composition is between about 0.1 μg and about 1000 μg, e.g., between about 75 μg and about 150 μg, e.g., about 100 μg. In some embodiments, the effective amount of the antigenic composition in the vaccine composition is between about 25 μg and about 75 μg. In some embodiments, the pharmaceutically acceptable vehicle comprises a saponin. In some embodiments, the vaccine composition comprises GM-CSF.
[0148] In some embodiments, the antigenic composition of the vaccine composition comprises (a) a first peptide comprising SEQ ID NO:25 or a variant thereof; and (b) a third peptide comprising SEQ ID NO:27 or a variant thereof, where each peptide comprises a T cell epitope and a B cell epitope. In some embodiments, the two or more labyrinthin-derived peptides are 21 to 24 amino acids in length, for example 22 or 23 amino acids in length. In some embodiments, the first peptide comprising SEQ ID NO:25 or a variant thereof comprises SEQ ID NO:29 or a variant thereof. In some embodiments, the first peptide comprising SEQ ID NO:25 or a variant thereof has sequence similarity of at least about 90% similarity, for example at least about 92% similarity, 95% similarity, or 97% similarity, to a portion of labyrinthin (SEQ ID NO:1). In some embodiments, the first peptide comprising SEQ ID NO:25 is SEQ ID NO:29. In some embodiments, the first peptide comprising SEQ ID NO:25 or a variant thereof is conjugated. In some embodiments, the third peptide comprising SEQ ID NO:27 or a variant thereof comprises SEQ ID NO:31 or a variant thereof. In some embodiments, the third peptide comprising SEQ ID NO:27 or a variant thereof has a sequence similarity of at least about 90% similarity, e.g., at least about 92% similarity, 95% similarity, or 97% similarity, to a portion of Labyrinthin (SEQ ID NO:1). In some embodiments, the third peptide comprising SEQ ID NO:27 is SEQ ID NO:31. In some embodiments, the third peptide comprising SEQ ID NO:27 or a variant thereof is conjugated. In some embodiments, the antigenic composition comprises (a) a first peptide comprising SEQ ID NO:29 or a variant thereof; and (b) a third peptide comprising SEQ ID NO:31 or a variant thereof, wherein each peptide comprises a T cell epitope and a B cell epitope. In some embodiments, the antigenic composition comprises (a) a first peptide, the first peptide being SEQ ID NO:29; and (b) a third peptide, the third peptide being SEQ ID NO:31, wherein each peptide comprises a T cell epitope and a B cell epitope.In some embodiments, the effective amount of the antigenic composition in the vaccine composition is between about 0.1 μg and about 1000 μg, such as between about 75 μg and about 150 μg, such as about 100 μg. In some embodiments, the effective amount of the antigenic composition in the vaccine composition is between about 25 μg and about 75 μg. In some embodiments, the pharmaceutically acceptable vehicle comprises a saponin. In some embodiments, the vaccine composition comprises GM-CSF.
[0149] In some embodiments, the antigenic composition of the vaccine composition comprises (a) a first peptide comprising SEQ ID NO:25 or a variant thereof; and (b) a fourth peptide comprising SEQ ID NO:28 or a variant thereof, each peptide comprising a T cell epitope and a B cell epitope. In some embodiments, the two or more labyrinthin-derived peptides are 21 to 24 amino acids in length, for example 22 or 23 amino acids in length. In some embodiments, the first peptide comprising SEQ ID NO:25 or a variant thereof comprises SEQ ID NO:29 or a variant thereof. In some embodiments, the first peptide comprising SEQ ID NO:25 or a variant thereof has sequence similarity of at least about 90% similarity, for example at least about 92% similarity, 95% similarity, or 97% similarity, to a portion of labyrinthin (SEQ ID NO:1). In some embodiments, the first peptide comprising SEQ ID NO:25 is SEQ ID NO:29. In some embodiments, the first peptide comprising SEQ ID NO:25 or a variant thereof is conjugated. In some embodiments, the fourth peptide comprising SEQ ID NO:28 or a variant thereof comprises SEQ ID NO:32 or a variant thereof. In some embodiments, the fourth peptide comprising SEQ ID NO:28 or a variant thereof has a sequence similarity of at least about 90% similarity, e.g., at least about 92% similarity, 95% similarity, or 97% similarity, to a portion of Labyrinthin (SEQ ID NO:1). In some embodiments, the fourth peptide comprising SEQ ID NO:28 is SEQ ID NO:32. In some embodiments, the fourth peptide comprising SEQ ID NO:28 or a variant thereof is conjugated. In some embodiments, the antigenic composition comprises (a) a first peptide comprising SEQ ID NO:29 or a variant thereof; (b) a fourth peptide comprising SEQ ID NO:32 or a variant thereof, wherein each peptide comprises a T cell epitope and a B cell epitope. In some embodiments, the antigenic composition comprises (a) a first peptide, the first peptide being SEQ ID NO:29; and (b) a fourth peptide, the fourth peptide being SEQ ID NO:32, wherein each peptide comprises a T cell epitope and a B cell epitope.In some embodiments, the effective amount of the antigenic composition in the vaccine composition is between about 0.1 μg and about 1000 μg, such as between about 75 μg and about 150 μg, such as about 100 μg. In some embodiments, the effective amount of the antigenic composition in the vaccine composition is between about 25 μg and about 75 μg. In some embodiments, the pharmaceutically acceptable vehicle comprises a saponin. In some embodiments, the vaccine composition comprises GM-CSF.
[0150] In some embodiments, the antigenic composition of the vaccine composition comprises (a) a second peptide comprising SEQ ID NO:26 or a variant thereof; and (b) a third peptide comprising SEQ ID NO:27 or a variant thereof, where each peptide comprises a T cell epitope and a B cell epitope. In some embodiments, the two or more labyrinthin-derived peptides are 21 to 24 amino acids in length, for example, 22 or 23 amino acids in length. In some embodiments, the second peptide comprising SEQ ID NO:26 or a variant thereof comprises SEQ ID NO:30 or a variant thereof. In some embodiments, the second peptide comprising SEQ ID NO:30 or a variant thereof has sequence similarity of at least about 90% similarity, for example, at least about 92% similarity, 95% similarity, or 97% similarity, to a portion of labyrinthin (SEQ ID NO:1). In some embodiments, the second peptide comprising SEQ ID NO:26 is SEQ ID NO:30. In some embodiments, the second peptide comprising SEQ ID NO:26 or a variant thereof is conjugated. In some embodiments, the third peptide comprising SEQ ID NO:27 or a variant thereof comprises SEQ ID NO:31 or a variant thereof. In some embodiments, the third peptide comprising SEQ ID NO:27 or a variant thereof has a sequence similarity of at least about 90% similarity, e.g., at least about 92% similarity, 95% similarity, or 97% similarity, to a portion of Labyrinthin (SEQ ID NO:1). In some embodiments, the third peptide comprising SEQ ID NO:27 is SEQ ID NO:31. In some embodiments, the third peptide comprising SEQ ID NO:27 or a variant thereof is conjugated. In some embodiments, the antigenic composition comprises (a) a second peptide comprising SEQ ID NO:30 or a variant thereof; and (b) a third peptide comprising SEQ ID NO:31 or a variant thereof, wherein each peptide comprises a T cell epitope and a B cell epitope. In some embodiments, the antigenic composition comprises (a) a second peptide, the second peptide being SEQ ID NO:30; and (b) a third peptide, the third peptide being SEQ ID NO:31, wherein each peptide comprises a T cell epitope and a B cell epitope.In some embodiments, the effective amount of the antigenic composition in the vaccine composition is between about 0.1 μg and about 1000 μg, such as between about 75 μg and about 150 μg, such as about 100 μg. In some embodiments, the effective amount of the antigenic composition in the vaccine composition is between about 25 μg and about 75 μg. In some embodiments, the pharmaceutically acceptable vehicle comprises a saponin. In some embodiments, the vaccine composition comprises GM-CSF.
[0151] In some embodiments, the antigenic composition of the vaccine composition comprises (a) a second peptide comprising SEQ ID NO:26 or a variant thereof; and (b) a fourth peptide comprising SEQ ID NO:28 or a variant thereof, where each peptide comprises a T cell epitope and a B cell epitope. In some embodiments, the two or more labyrinthin-derived peptides are 21 to 24 amino acids in length, for example, 22 or 23 amino acids in length. In some embodiments, the second peptide comprising SEQ ID NO:26 or a variant thereof comprises SEQ ID NO:30 or a variant thereof. In some embodiments, the second peptide comprising SEQ ID NO:30 or a variant thereof has sequence similarity of at least about 90% similarity, for example, at least about 92% similarity, 95% similarity, or 97% similarity, to a portion of labyrinthin (SEQ ID NO:1). In some embodiments, the second peptide comprising SEQ ID NO:26 is SEQ ID NO:30. In some embodiments, the second peptide comprising SEQ ID NO:26 or a variant thereof is conjugated. In some embodiments, the fourth peptide comprising SEQ ID NO:28 or a variant thereof comprises SEQ ID NO:32 or a variant thereof. In some embodiments, the fourth peptide comprising SEQ ID NO:28 or a variant thereof has a sequence similarity of at least about 90% similarity, e.g., at least about 92% similarity, 95% similarity, or 97% similarity, to a portion of Labyrinthin (SEQ ID NO:1). In some embodiments, the fourth peptide comprising SEQ ID NO:28 is SEQ ID NO:32. In some embodiments, the fourth peptide comprising SEQ ID NO:28 or a variant thereof is conjugated. In some embodiments, the antigenic composition comprises (a) a second peptide comprising SEQ ID NO:30 or a variant thereof; and (b) a fourth peptide comprising SEQ ID NO:32 or a variant thereof, wherein each peptide comprises a T cell epitope and a B cell epitope. In some embodiments, the antigenic composition comprises (a) a second peptide, the second peptide being SEQ ID NO:30; and (b) a fourth peptide, the fourth peptide being SEQ ID NO:32, wherein each peptide comprises a T cell epitope and a B cell epitope.In some embodiments, the effective amount of the antigenic composition in the vaccine composition is between about 0.1 μg and about 1000 μg, such as between about 75 μg and about 150 μg, such as about 100 μg. In some embodiments, the effective amount of the antigenic composition in the vaccine composition is between about 25 μg and about 75 μg. In some embodiments, the pharmaceutically acceptable vehicle comprises a saponin. In some embodiments, the vaccine composition comprises GM-CSF.
[0152] In some embodiments, the antigenic composition of the vaccine composition comprises (a) a third peptide comprising SEQ ID NO:27 or a variant thereof; and (b) a fourth peptide comprising SEQ ID NO:28 or a variant thereof, where each peptide comprises a T cell epitope and a B cell epitope. In some embodiments, the two or more labyrinthin-derived peptides are 21 to 24 amino acids in length, for example, 22 or 23 amino acids in length. In some embodiments, the third peptide comprising SEQ ID NO:27 or a variant thereof comprises SEQ ID NO:31 or a variant thereof. In some embodiments, the third peptide comprising SEQ ID NO:27 or a variant thereof has sequence similarity of at least about 90% similarity, for example, at least about 92% similarity, 95% similarity, or 97% similarity, to a portion of labyrinthin (SEQ ID NO:1). In some embodiments, the third peptide comprising SEQ ID NO:27 is SEQ ID NO:31. In some embodiments, the third peptide comprising SEQ ID NO:27 or a variant thereof is conjugated. In some embodiments, the fourth peptide comprising SEQ ID NO:28 or a variant thereof comprises SEQ ID NO:32 or a variant thereof. In some embodiments, the fourth peptide comprising SEQ ID NO:28 or a variant thereof has a sequence similarity of at least about 90% similarity, e.g., at least about 92% similarity, 95% similarity, or 97% similarity, to a portion of Labyrinthin (SEQ ID NO:1). In some embodiments, the fourth peptide comprising SEQ ID NO:28 is SEQ ID NO:32. In some embodiments, the fourth peptide comprising SEQ ID NO:28 or a variant thereof is conjugated. In some embodiments, the antigenic composition comprises (a) a third peptide comprising SEQ ID NO:31 or a variant thereof; and (b) a fourth peptide comprising SEQ ID NO:32 or a variant thereof, wherein each peptide comprises a T cell epitope and a B cell epitope. In some embodiments, the antigenic composition comprises (a) a third peptide, the third peptide being SEQ ID NO:31; and (b) a fourth peptide, the fourth peptide being SEQ ID NO:32, wherein each peptide comprises a T cell epitope and a B cell epitope.In some embodiments, the effective amount of the antigenic composition in the vaccine composition is between about 0.1 μg and about 1000 μg, such as between about 75 μg and about 150 μg, such as about 100 μg. In some embodiments, the effective amount of the antigenic composition in the vaccine composition is between about 25 μg and about 75 μg. In some embodiments, the pharmaceutically acceptable vehicle comprises a saponin. In some embodiments, the vaccine composition comprises GM-CSF.
[0153] In some embodiments, the antigenic composition of the vaccine composition comprises three or more labyrinthin-derived peptides. For example, in some embodiments, the antigenic composition comprises (a) a first peptide comprising SEQ ID NO:25 or a variant thereof; (b) a second peptide comprising SEQ ID NO:26 or a variant thereof; and (c) a third peptide comprising SEQ ID NO:27 or a variant thereof, wherein each peptide comprises a T cell epitope and a B cell epitope. In some embodiments, each of the three or more labyrinthin-derived peptides is 21 to 24 amino acids in length, e.g., 22 or 23 amino acids in length. In some embodiments, the first peptide comprising SEQ ID NO:25 or a variant thereof comprises SEQ ID NO:29 or a variant thereof. In some embodiments, the first peptide comprising SEQ ID NO:25 or a variant thereof has a sequence similarity of at least about 90% similarity, e.g., at least about any of 92% similarity, 95% similarity, or 97% similarity, to a portion of labyrinthin (SEQ ID NO:1). In some embodiments, the first peptide comprising SEQ ID NO:25 is SEQ ID NO:29. In some embodiments, the first peptide comprising SEQ ID NO:25 or a variant thereof is conjugated. In some embodiments, the second peptide comprising SEQ ID NO:26 or a variant thereof comprises SEQ ID NO:30 or a variant thereof. In some embodiments, the second peptide comprising SEQ ID NO:30 or a variant thereof has a sequence similarity of at least about 90% similarity, for example at least about 92% similarity, 95% similarity, or 97% similarity, to a portion of Labyrinthin (SEQ ID NO:1). In some embodiments, the second peptide comprising SEQ ID NO:26 is SEQ ID NO:30. In some embodiments, the second peptide comprising SEQ ID NO:26 or a variant thereof is conjugated. In some embodiments, the third peptide comprising SEQ ID NO:27 or a variant thereof comprises SEQ ID NO:31 or a variant thereof. In some embodiments, the third peptide comprising SEQ ID NO:27 or a variant thereof has sequence similarity to a portion of Labyrinthin (SEQ ID NO:1) of at least about 90% similarity, e.g., at least about 92% similarity, 95% similarity, or 97% similarity.In some embodiments, the third peptide comprising SEQ ID NO:27 is SEQ ID NO:31. In some embodiments, the third peptide comprising SEQ ID NO:27 or a variant thereof is conjugated. In some embodiments, the antigenic composition comprises (a) a first peptide comprising SEQ ID NO:29 or a variant thereof; (b) a second peptide comprising SEQ ID NO:30 or a variant thereof; and (c) a third peptide comprising SEQ ID NO:31 or a variant thereof, wherein each peptide comprises a T cell epitope and a B cell epitope. In some embodiments, the antigenic composition comprises (a) a first peptide, the first peptide being SEQ ID NO:29; (b) a second peptide, the second peptide being SEQ ID NO:30; and (c) a third peptide, the third peptide being SEQ ID NO:31, wherein each peptide comprises a T cell epitope and a B cell epitope. In some embodiments, the effective amount of the antigenic composition in the vaccine composition is between about 0.1 μg and about 1000 μg, such as between about 75 μg and about 150 μg, such as about 100 μg. In some embodiments, the effective amount of the antigenic composition in the vaccine composition is between about 25 μg and about 75 μg. In some embodiments, the pharmaceutically acceptable vehicle comprises a saponin. In some embodiments, the vaccine composition comprises GM-CSF.
[0154] In some embodiments, the antigenic composition of the vaccine composition comprises (a) a first peptide comprising SEQ ID NO:25 or a variant thereof; (b) a second peptide comprising SEQ ID NO:26 or a variant thereof; and (c) a fourth peptide comprising SEQ ID NO:28 or a variant thereof, wherein each peptide comprises a T cell epitope and a B cell epitope. In some embodiments, each of the three or more labyrinthin-derived peptides is 21 to 24 amino acids in length, e.g., 22 or 23 amino acids in length. In some embodiments, the first peptide comprising SEQ ID NO:25 or a variant thereof comprises SEQ ID NO:29 or a variant thereof. In some embodiments, the first peptide comprising SEQ ID NO:25 or a variant thereof has sequence similarity of at least about 90% similarity, e.g., at least about 92% similarity, 95% similarity, or 97% similarity, to a portion of labyrinthin (SEQ ID NO:1). In some embodiments, the first peptide comprising SEQ ID NO:25 is SEQ ID NO:29. In some embodiments, the first peptide comprising SEQ ID NO:25 or a variant thereof is conjugated. In some embodiments, the second peptide comprising SEQ ID NO:26 or a variant thereof comprises SEQ ID NO:30 or a variant thereof. In some embodiments, the second peptide comprising SEQ ID NO:30 or a variant thereof has a sequence similarity of at least about 90% similarity, for example at least about 92% similarity, 95% similarity, or 97% similarity, to a portion of Labyrinthin (SEQ ID NO:1). In some embodiments, the second peptide comprising SEQ ID NO:26 is SEQ ID NO:30. In some embodiments, the second peptide comprising SEQ ID NO:26 or a variant thereof is conjugated. In some embodiments, the fourth peptide comprising SEQ ID NO:28 or a variant thereof comprises SEQ ID NO:32 or a variant thereof. In some embodiments, the fourth peptide comprising SEQ ID NO:28 or a variant thereof has sequence similarity of at least about 90% to a portion of Labyrinthin (SEQ ID NO:1), e.g., at least about 92% similarity, 95% similarity, or 97% similarity. In some embodiments, the fourth peptide comprising SEQ ID NO:28 is SEQ ID NO:32.In some embodiments, the fourth peptide comprising SEQ ID NO:28 or a variant thereof is conjugated. In some embodiments, the antigenic composition comprises (a) a first peptide comprising SEQ ID NO:29 or a variant thereof; (b) a second peptide comprising SEQ ID NO:30 or a variant thereof; and (c) a fourth peptide comprising SEQ ID NO:32 or a variant thereof, wherein each peptide comprises a T cell epitope and a B cell epitope. In some embodiments, the antigenic composition comprises (a) a first peptide, the first peptide being SEQ ID NO:29; (b) a second peptide, the second peptide being SEQ ID NO:30; and (c) a fourth peptide, the fourth peptide being SEQ ID NO:32, wherein each peptide comprises a T cell epitope and a B cell epitope. In some embodiments, the effective amount of the antigenic composition in the vaccine composition is between about 0.1 μg and about 1000 μg, e.g., between about 75 μg and about 150 μg, e.g., about 100 μg. In some embodiments, the effective amount of the antigenic composition of the vaccine composition is between about 25 μg and about 75 μg. In some embodiments, the pharma- ceutically acceptable vehicle comprises a saponin. In some embodiments, the vaccine composition comprises GM-CSF.
[0155] In some embodiments, the antigenic composition of the vaccine composition comprises (a) a first peptide comprising SEQ ID NO:25 or a variant thereof; (b) a third peptide comprising SEQ ID NO:26 or a variant thereof; and (c) a fourth peptide comprising SEQ ID NO:28 or a variant thereof, wherein each peptide comprises a T cell epitope and a B cell epitope. In some embodiments, each of the three or more labyrinthin-derived peptides is 21 to 24 amino acids in length, e.g., 22 or 23 amino acids in length. In some embodiments, the first peptide comprising SEQ ID NO:25 or a variant thereof comprises SEQ ID NO:29 or a variant thereof. In some embodiments, the first peptide comprising SEQ ID NO:25 or a variant thereof has sequence similarity of at least about 90% similarity, e.g., at least about any of 92% similarity, 95% similarity, or 97% similarity, to a portion of labyrinthin (SEQ ID NO:1). In some embodiments, the first peptide comprising SEQ ID NO:25 is SEQ ID NO:29. In some embodiments, the first peptide comprising SEQ ID NO:25 or a variant thereof is conjugated. In some embodiments, the third peptide comprising SEQ ID NO:27 or a variant thereof comprises SEQ ID NO:31 or a variant thereof. In some embodiments, the third peptide comprising SEQ ID NO:27 or a variant thereof has a sequence similarity of at least about 90% similarity, for example at least about 92% similarity, 95% similarity, or 97% similarity, to a portion of Labyrinthin (SEQ ID NO:1). In some embodiments, the third peptide comprising SEQ ID NO:27 is SEQ ID NO:31. In some embodiments, the third peptide comprising SEQ ID NO:27 or a variant thereof is conjugated. In some embodiments, the fourth peptide comprising SEQ ID NO:28 or a variant thereof comprises SEQ ID NO:32 or a variant thereof. In some embodiments, the fourth peptide comprising SEQ ID NO:28 or a variant thereof has sequence similarity of at least about 90% to a portion of Labyrinthin (SEQ ID NO:1), e.g., at least about 92% similarity, 95% similarity, or 97% similarity. In some embodiments, the fourth peptide comprising SEQ ID NO:28 is SEQ ID NO:32.In some embodiments, the fourth peptide comprising SEQ ID NO:28 or a variant thereof is conjugated. In some embodiments, the antigenic composition comprises (a) a first peptide comprising SEQ ID NO:29 or a variant thereof; (b) a third peptide comprising SEQ ID NO:31 or a variant thereof; and (c) a fourth peptide comprising SEQ ID NO:32 or a variant thereof, wherein each peptide comprises a T cell epitope and a B cell epitope. In some embodiments, the antigenic composition comprises (a) a first peptide, the first peptide being SEQ ID NO:29; (b) a third peptide, the third peptide being SEQ ID NO:31; and (c) a fourth peptide, the fourth peptide being SEQ ID NO:32, wherein each peptide comprises a T cell epitope and a B cell epitope. In some embodiments, the effective amount of the antigenic composition in the vaccine composition is between about 0.1 μg and about 1000 μg, e.g., between about 75 μg and about 150 μg, e.g., about 100 μg. In some embodiments, the effective amount of the antigenic composition of the vaccine composition is between about 25 μg and about 75 μg. In some embodiments, the pharma- ceutically acceptable vehicle comprises a saponin. In some embodiments, the vaccine composition comprises GM-CSF.
[0156] In some embodiments, the antigenic composition of the vaccine composition comprises (a) a second peptide comprising SEQ ID NO:26 or a variant thereof; (b) a third peptide comprising SEQ ID NO:27 or a variant thereof; and (c) a fourth peptide comprising SEQ ID NO:28 or a variant thereof, wherein each peptide comprises a T cell epitope and a B cell epitope. In some embodiments, each of the three or more labyrinthin-derived peptides is 21 to 24 amino acids in length, e.g., 22 or 23 amino acids in length. In some embodiments, the second peptide comprising SEQ ID NO:26 or a variant thereof comprises SEQ ID NO:30 or a variant thereof. In some embodiments, the second peptide comprising SEQ ID NO:30 or a variant thereof has sequence similarity of at least about 90% similarity, e.g., at least about 92% similarity, 95% similarity, or 97% similarity, to a portion of labyrinthin (SEQ ID NO:1). In some embodiments, the second peptide comprising SEQ ID NO:26 is SEQ ID NO:30. In some embodiments, the second peptide comprising SEQ ID NO:26 or a variant thereof is conjugated. In some embodiments, the third peptide comprising SEQ ID NO:27 or a variant thereof comprises SEQ ID NO:31 or a variant thereof. In some embodiments, the third peptide comprising SEQ ID NO:27 or a variant thereof has a sequence similarity of at least about 90% similarity, for example at least about 92% similarity, 95% similarity, or 97% similarity, to a portion of Labyrinthin (SEQ ID NO:1). In some embodiments, the third peptide comprising SEQ ID NO:27 is SEQ ID NO:31. In some embodiments, the third peptide comprising SEQ ID NO:27 or a variant thereof is conjugated. In some embodiments, the fourth peptide comprising SEQ ID NO:28 or a variant thereof comprises SEQ ID NO:32 or a variant thereof. In some embodiments, the fourth peptide comprising SEQ ID NO:28 or a variant thereof has sequence similarity of at least about 90% to a portion of Labyrinthin (SEQ ID NO:1), e.g., at least about 92% similarity, 95% similarity, or 97% similarity. In some embodiments, the fourth peptide comprising SEQ ID NO:28 is SEQ ID NO:32.In some embodiments, the fourth peptide comprising SEQ ID NO:28 or a variant thereof is conjugated. In some embodiments, the antigenic composition comprises (a) a second peptide comprising SEQ ID NO:30 or a variant thereof; (b) a third peptide comprising SEQ ID NO:31 or a variant thereof; and (c) a fourth peptide comprising SEQ ID NO:32 or a variant thereof, wherein each peptide comprises a T cell epitope and a B cell epitope. In some embodiments, the antigenic composition comprises (a) a second peptide, the second peptide being SEQ ID NO:30; (b) a third peptide, the third peptide being SEQ ID NO:31; and (c) a fourth peptide, the fourth peptide being SEQ ID NO:32, wherein each peptide comprises a T cell epitope and a B cell epitope. In some embodiments, the effective amount of the antigenic composition in the vaccine composition is between about 0.1 μg and about 1000 μg, e.g., between about 75 μg and about 150 μg, e.g., about 100 μg. In some embodiments, the effective amount of the antigenic composition of the vaccine composition is between about 25 μg and about 75 μg. In some embodiments, the pharma- ceutically acceptable vehicle comprises a saponin. In some embodiments, the vaccine composition comprises GM-CSF.
[0157] In some embodiments, the antigenic composition of the vaccine composition comprises four or more labyrinthin-derived peptides. For example, in some embodiments, the antigenic composition of the vaccine composition comprises (a) a first peptide comprising SEQ ID NO:25 or a variant thereof; (b) a second peptide comprising SEQ ID NO:26 or a variant thereof; (c) a third peptide comprising SEQ ID NO:27 or a variant thereof; and (d) a fourth peptide comprising SEQ ID NO:28 or a variant thereof, wherein each peptide comprises a T cell epitope and a B cell epitope. In some embodiments, each of the four or more labyrinthin-derived peptides is 21 to 24 amino acids in length, e.g., 22 or 23 amino acids in length. In some embodiments, the first peptide comprising SEQ ID NO:25 or a variant thereof comprises SEQ ID NO:29 or a variant thereof. In some embodiments, the first peptide comprising SEQ ID NO:25 or a variant thereof has at least about 90% sequence similarity, e.g., at least about 92% sequence similarity, 95% sequence similarity, or 97% sequence similarity, to a portion of labyrinthin (SEQ ID NO:1). In some embodiments, the first peptide comprising SEQ ID NO:25 is SEQ ID NO:29. In some embodiments, the first peptide comprising SEQ ID NO:25 or a variant thereof is conjugated. In some embodiments, the second peptide comprising SEQ ID NO:26 or a variant thereof comprises SEQ ID NO:30 or a variant thereof. In some embodiments, the second peptide comprising SEQ ID NO:30 or a variant thereof has at least about 90% sequence similarity, e.g., at least about 92% sequence similarity, 95% sequence similarity, or 97% sequence similarity, to a portion of labyrinthin (SEQ ID NO:1). In some embodiments, the second peptide comprising SEQ ID NO:26 is SEQ ID NO:30. In some embodiments, the second peptide comprises SEQ ID NO:26 or a variant thereof, and the third peptide comprises SEQ ID NO:31 or a variant thereof.In some embodiments, the third peptide comprising SEQ ID NO:27 or a variant thereof has a sequence similarity of at least about 90% to a portion of labyrinthin (SEQ ID NO:1), e.g., at least about 92% similarity, 95% similarity, or 97% similarity. In some embodiments, the third peptide comprising SEQ ID NO:27 is SEQ ID NO:31. In some embodiments, the third peptide comprising SEQ ID NO:27 or a variant thereof is conjugated. In some embodiments, the fourth peptide comprising SEQ ID NO:28 or a variant thereof comprises SEQ ID NO:32 or a variant thereof. In some embodiments, the fourth peptide comprising SEQ ID NO:28 or a variant thereof has a sequence similarity of at least about 90% to a portion of labyrinthin (SEQ ID NO:1), e.g., at least about 92% similarity, 95% similarity, or 97% similarity. In some embodiments, the fourth peptide comprising SEQ ID NO:28 is SEQ ID NO:32. In some embodiments, the fourth peptide comprising SEQ ID NO:28 or a variant thereof is conjugated. In some embodiments, the antigenic composition comprises (a) a first peptide comprising SEQ ID NO:29 or a variant thereof; (b) a second peptide comprising SEQ ID NO:30 or a variant thereof; (c) a third peptide comprising SEQ ID NO:31 or a variant thereof; and (d) a fourth peptide comprising SEQ ID NO:32 or a variant thereof, wherein each peptide comprises a T cell epitope and a B cell epitope. In some embodiments, the antigenic composition comprises (a) a first peptide, the first peptide being SEQ ID NO:29; (b) a second peptide, the second peptide being SEQ ID NO:30; (c) a third peptide, the third peptide being SEQ ID NO:31; and (d) a fourth peptide, the fourth peptide being SEQ ID NO:32, wherein each peptide comprises a T cell epitope and a B cell epitope. In some embodiments, the effective amount of the antigenic composition in the vaccine composition is between about 0.1 μg and about 1000 μg, such as between about 75 μg and about 150 μg, such as about 100 μg. In some embodiments, the effective amount of the antigenic composition in the vaccine composition is between about 25 μg and about 75 μg.In some embodiments, the pharma- ceutically acceptable vehicle comprises saponin. In some embodiments, the vaccine composition comprises GM-CSF. In some embodiments, the vaccine composition is LabVax 3(22)-23.
[0158] In some embodiments, the vaccine composition comprises one or more labyrinthin-derived peptides selected from the group consisting of: (a) a first peptide comprising SEQ ID NO:25 or a variant thereof; (b) a second peptide comprising SEQ ID NO:26 or a variant thereof; (c) a third peptide comprising SEQ ID NO:27 or a variant thereof; and (d) a fourth peptide comprising SEQ ID NO:28 or a variant thereof. In some embodiments, the vaccine composition comprises: (a) a first peptide comprising SEQ ID NO:25 or a variant thereof; (b) a second peptide comprising SEQ ID NO:26 or a variant thereof; (c) a third peptide comprising SEQ ID NO:27 or a variant thereof; and (d) a fourth peptide comprising SEQ ID NO:28 or a variant thereof. In some embodiments, the vaccine composition comprises (a) a first peptide comprising SEQ ID NO:25 or a variant thereof; (b) a second peptide comprising SEQ ID NO:26 or a variant thereof; (c) a third peptide comprising SEQ ID NO:27 or a variant thereof; and (d) a fourth peptide comprising SEQ ID NO:28 or a variant thereof, wherein these four peptides are the only labyrinthin-derived peptides in the vaccine composition. In some embodiments, the labyrinthin-derived peptide is 21 to 24 amino acids in length, for example 22 or 23 amino acids in length. In some embodiments, the vaccine composition comprising a peptide comprising SEQ ID NO:25 or a variant thereof comprises SEQ ID NO:29 or a variant thereof. In some embodiments, the vaccine composition comprising a peptide comprising SEQ ID NO:26 or a variant thereof comprises SEQ ID NO:30 or a variant thereof. In some embodiments, the vaccine composition comprising a peptide comprising SEQ ID NO:27 or a variant thereof comprises SEQ ID NO:31 or a variant thereof. In some embodiments, the vaccine composition comprising a peptide comprising SEQ ID NO:28 or a variant thereof comprises SEQ ID NO:32 or a variant thereof.In some embodiments, the vaccine composition comprises (a) a first peptide comprising SEQ ID NO:29 or a variant thereof; (b) a second peptide comprising SEQ ID NO:30 or a variant thereof; (c) a third peptide comprising SEQ ID NO:31 or a variant thereof; and (d) a fourth peptide comprising SEQ ID NO:32 or a variant thereof, wherein these four peptides are the only labyrinthin-derived peptides in the vaccine composition. In some embodiments, the vaccine composition consists essentially of (a) a first peptide comprising SEQ ID NO:29 or a variant thereof; (b) a second peptide comprising SEQ ID NO:30 or a variant thereof; (c) a third peptide comprising SEQ ID NO:31 or a variant thereof; and (d) a fourth peptide comprising SEQ ID NO:32 or a variant thereof, wherein these four peptides are the only labyrinthin-derived peptides in the vaccine composition. In some embodiments, the labyrinthin-derived peptide comprises a T cell epitope and / or a B cell epitope. In some embodiments, the effective amount of the antigenic composition in the vaccine composition is between about 0.1 μg and about 1000 μg, such as between about 75 μg and about 150 μg, such as about 100 μg. In some embodiments, the vaccine composition comprises GM-CSF. In some embodiments, the vaccine composition is LabVax 3(22)-23.
[0159] In some embodiments, the vaccine composition comprises four labyrinthin-derived peptides, wherein the four labyrinthin-derived peptides are SEQ ID NOs:29-32, and these four peptides are the only labyrinthin-derived peptides in the vaccine composition, each peptide is present in an amount of 100 μg, and the volume of the vaccine is about 0.1 mL. In some embodiments, the vaccine composition is LabVax 3(22)-23. In some embodiments, LabVax 3(22)-23 further comprises GM-CSF.
[0160] [Kits, pharmaceuticals, and compositions thereof] The present disclosure provides, in some aspects, kits, medicaments, and compositions, including pharmaceutical compositions and unit dosage forms, that include the antigenic compositions disclosed herein. In some aspects, the present disclosure provides vaccine compositions, including kits, medicaments, and compositions thereof, including pharmaceutical compositions and unit dosage forms, that include the antigenic compositions disclosed herein.
[0161] In some embodiments, the kits of the present disclosure may include one or more containers containing an antigenic composition and / or vaccine composition (or unit dosage and / or article of manufacture thereof) described herein. In some embodiments, the kits further include one or more containers containing another agent (or unit dosage and / or article of manufacture thereof), such as an adjuvant, including an immunologically effective adjuvant such as GM-CSF. In some embodiments, the kits further include instructions for use according to any of the methods disclosed herein. The kits may also include a description of criteria for selecting individuals suitable for treatment by any of the methods disclosed herein. Instructions provided with the kits disclosed herein are typically written instructions on a label or insert (e.g., a paper sheet included in the kit), although machine-readable instructions (e.g., instructions carried on a magnetic or optical storage disk) are also acceptable.
[0162] In some embodiments, compositions comprising the antigenic compositions described herein, such as vaccine compositions, may be present in separate containers or in a single container.
[0163] In some embodiments, the kits of the present disclosure are in suitable packaging. Suitable packaging includes, but is not limited to, vials, bottles, jars, flexible packaging (e.g., sealed Mylar or plastic bags), and the like. The kits may optionally provide additional components, such as buffers, interpretive information, and the like. Thus, the present application also provides articles of manufacture that include vials (such as sealed vials), bottles, jars, flexible packaging, and the like.
[0164] Also provided in the disclosure are pharmaceutical agents and compositions (such as unit dosage forms) useful in the methods described herein. For example, in some embodiments, there is provided the use of a composition, including an antigenic composition, such as a vaccine composition, for the treatment of cancer in an individual in need thereof.
[0165] [How to use it] The disclosure provides, in some aspects, methods of using the vaccine compositions described herein. In some aspects, the disclosure provides methods for treating cancer in an individual in need of treatment, comprising administering to the individual a vaccine composition described herein. In other aspects, the disclosure provides methods for preventing cancer in an individual in need of prevention, comprising administering to the individual a vaccine composition described herein. In some embodiments, the cancer is a labyrinthin-positive cancer. In some embodiments, the cancer is an adenocarcinoma, such as a labyrinthin-positive adenocarcinoma.
[0166] In some embodiments, a method for treating cancer comprises administering to an individual a vaccine composition, the vaccine composition comprising (i) an effective amount of an antigenic composition comprising one or more labyrinthin-derived peptides, the labyrinthin-derived peptides comprising a sequence selected from SEQ ID NOs:2-32 or variants thereof; and (ii) a pharmaceutically acceptable vehicle. In some embodiments, the labyrinthin-derived peptides comprising a sequence selected from SEQ ID NOs:2-32 (Table 2) or variants thereof comprise amino acid sequences flanking one or more termini of the core sequence provided in SEQ ID NOs:2-32.
[0167] In some embodiments, a method for preventing cancer comprises administering to an individual a vaccine composition, the vaccine composition comprising (i) an effective amount of an antigenic composition comprising one or more labyrinthin-derived peptides, the labyrinthin-derived peptides comprising a sequence selected from SEQ ID NOs:2-32 or variants thereof; and (ii) a pharmaceutically acceptable vehicle. In some embodiments, the labyrinthin-derived peptides comprising a sequence selected from SEQ ID NOs:2-32 (Table 2) or variants thereof comprise amino acid sequences flanking one or more termini of the core sequence provided in SEQ ID NOs:2-32.
[0168] In some embodiments, a method for treating cancer in an individual comprises administering to the individual a vaccine composition described herein, wherein the labyrinthin status of the cancer is used as a basis for selecting the individual for treatment. In some embodiments, the labyrinthin status of the cancer refers to labyrinthin expression in the cancer (e.g., labyrinthin overexpression compared to a control, e.g., healthy or non-cancerous tissue of the individual). In some embodiments, the labyrinthin status of the cancer refers to labyrinthin presentation on the cell surface of the cancer. In some embodiments, an individual is selected for treatment if a cancer sample from an individual shows that any of about 10% or more, e.g., at least about 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 75%, 80%, 85%, 90%, or 95% of the cancer cells in the sample are positive for labyrinthin, as determined, for example, using immunohistochemistry (IHC) methods. In some embodiments, an individual is selected for treatment if a cancer sample from the individual shows that about 10% or more, e.g., at least about any of 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 75%, 80%, 85%, 90%, or 95%, of a subpopulation of cancerous cells in the sample, such as cells surrounding a tumor, are positive for Labyrinthin, as determined, for example, using immunohistochemistry (IHC) methods.
[0169] In some embodiments, disclosed herein are methods for treating labyrinthin-positive cancer in an individual, the method comprising administering to the individual a vaccine composition, wherein the vaccine composition comprises an effective amount of an antigenic composition comprising: (a) a first peptide comprising SEQ ID NO:29 or a variant thereof; (b) a second peptide comprising SEQ ID NO:30 or a variant thereof; (c) a third peptide comprising SEQ ID NO:31 or a variant thereof; and (d) a fourth peptide comprising SEQ ID NO:32 or a variant thereof. In some embodiments, each peptide comprises a T cell epitope and a B cell epitope. In some embodiments, the effective amount of the antigenic composition in the vaccine composition is between about 0.1 μg and about 1000 μg, such as between about 75 μg and about 150 μg, such as about 100 μg. In some embodiments, the effective amount of the antigenic composition in the vaccine composition is between about 25 μg and about 75 μg. In some embodiments, the vaccine composition is LabVax 3(22)-23. In some embodiments, the method further comprises selecting an individual for treatment based on the labyrinthin status of the cancer, which indicates labyrinthin-positive cancer. In some embodiments, the labyrinthin status of the cancer is determined using immunohistochemistry (IHC) method, and about 10% or more of the cancerous cells in a sample from the individual are positive for labyrinthin, indicating labyrinthin-positive cancer. In some embodiments, the labyrinthin-positive cancer is adenocarcinoma.
[0170] The methods disclosed herein may include administering multiple doses of the vaccine composition described herein to an individual over a period of time. For example, the vaccine composition described herein may be administered repeatedly to an individual over a period of time until the individual develops an appropriate immunogenic response to the components of the vaccine composition. In some embodiments, the methods include administering the vaccine composition to an individual in need thereof, where the individual receives about 1 to about 10 separate doses of the vaccine composition. In some embodiments, the methods include administering the vaccine composition to an individual in need thereof, where the individual receives 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 separate doses of the vaccine composition. In some embodiments, the methods include administering the vaccine composition to an individual in need thereof, where the individual receives at least 1 dose, e.g., at least any of 2, 3, 4, 5, 6, 7, 8, 9, or 10 separate doses of the vaccine composition. In some embodiments, the method comprises administering the vaccine composition to an individual in need thereof, where the individual receives at least one separate administration of the vaccine composition over a period of about six months. In some embodiments, the method comprises administering the vaccine composition to an individual in need thereof, where the individual receives at least four separate administrations of the vaccine composition over a period of about six months. In some embodiments, the method comprises administering the vaccine composition to an individual in need thereof, where the individual receives at least ten separate administrations of the vaccine composition over a period of about six months. In some embodiments, the separate administrations of the vaccine composition are spaced apart by about one week. In some embodiments, the method comprises administering the vaccine composition to an individual in need thereof, such as via intradermal administration, where the individual receives at least five separate administrations of the vaccine composition over a period of 12 weeks. In some embodiments, the method comprises administering the vaccine composition to an individual in need thereof, such as via intradermal administration, where the individual receives at least seven separate administrations of the vaccine composition over a period of 36 weeks. In some embodiments, one or more booster vaccinations are administered to an individual in need thereof.In some embodiments, the methods include administering a vaccine composition to an individual, where subsequent administrations of the vaccine composition to the individual are adjusted (such as by frequency of administration, time interval between administrations, or dosage), In some embodiments, the frequency of administration and / or dosage of the vaccine composition are adjusted over the course of treatment based on the judgment of the administering physician.
[0171] Vaccine compositions may be administered via a number of routes of administration. For example, agents described herein may be administered to an individual (such as a human) parenterally, including intravenously, intraarterially, intraperitoneally, intrapulmonary, orally, by inhalation, intravesicular, intramuscular, intratracheal, subcutaneously, intraocular, intrathecal, intradermal, or transdermal. In some embodiments, agents described herein, such as vaccine compositions, are administered intradermally, such as via intradermal injection. In some embodiments, vaccine compositions described herein are administered intradermally, where each injection in a vaccination series is administered at a different site (e.g., at least 3 cm away from the previous injection). In some embodiments where the route of administration is intradermal, the administration needle or syringe is held in place for at least about 3 minutes to about 5 minutes after injection of the vaccine composition.
[0172] In some embodiments, the method for treating and / or preventing cancer in an individual further comprises administering to the individual another agent. In some embodiments, the other agent is an adjuvant. In some embodiments, the adjuvant is granulocyte-macrophage colony stimulating factor (GM-CSF). In some embodiments, the adjuvant is GM-CSF of the organism for which the vaccine is intended to be administered, e.g., human GM-CSF. In some embodiments, the method comprises administering GM-CSF separately from the vaccine composition. In some embodiments, the other agent is a chemotherapeutic agent. In some embodiments, the GM-CSF is administered separately from the vaccine composition, such as about 45 minutes to about 60 minutes prior to administration of the GM-CSF. In some embodiments, the other agent is an immune checkpoint inhibitor. In some embodiments, the vaccine composition described herein and the other agent are administered simultaneously. In some embodiments, the vaccine composition described herein and the other agent are administered sequentially. In some embodiments, the vaccine composition described herein and the other agent are administered in combination.
[0173] In some embodiments, a method for treating and / or preventing labyrinthin-positive cancer in an individual comprises administering to the individual (i) a vaccine composition, the vaccine composition comprising an effective amount of an antigenic composition comprising: (a) a first peptide comprising SEQ ID NO:29 or a variant thereof; (b) a second peptide comprising SEQ ID NO:30 or a variant thereof; (c) a third peptide comprising SEQ ID NO:31 or a variant thereof; and (d) a fourth peptide comprising SEQ ID NO:32 or a variant thereof; and (ii) a composition comprising GM-CSF. In some embodiments, the vaccine composition is administered intradermally to the individual and the composition comprising GM-CSF is administered subcutaneously to the individual. In some embodiments, the vaccine composition and the composition comprising GM-CSF are administered to the individual within 60 minutes of each other. In some embodiments, each peptide comprises a T cell epitope and a B cell epitope. In some embodiments, the effective amount of the antigenic composition in the vaccine composition is between about 0.1 μg and about 1000 μg, such as between about 75 μg and about 150 μg, such as about 100 μg. In some embodiments, the effective amount of the antigenic composition in the vaccine composition is between about 25 μg and about 75 μg. In some embodiments, the vaccine composition is LabVax 3(22)-23. In some embodiments, the method further comprises selecting the individual for treatment based on the labyrinthin status of the cancer indicative of labyrinthin-positive cancer. In some embodiments, the labyrinthin status of the cancer is indicative of labyrinthin-positive cancer when about 10% or more of the cancerous cells in a sample from the individual are positive for labyrinthin, such as determined using immunohistochemistry (IHC) methods. In some embodiments, the labyrinthin-positive cancer is an adenocarcinoma.
[0174] In some embodiments, the methods described herein for treating and / or preventing Labyrinthin-positive cancer in an individual comprise administering to the individual a vaccine composition described herein. In some embodiments, the methods further comprise administering an adjuvant, such as GM-CSF. In some embodiments, the vaccine composition comprises one or more Labyrinthin-derived peptides selected from the group comprising: (a) a first peptide comprising SEQ ID NO:25 or a variant thereof; (b) a second peptide comprising SEQ ID NO:26 or a variant thereof; (c) a third peptide comprising SEQ ID NO:27 or a variant thereof; and (d) a fourth peptide comprising SEQ ID NO:28 or a variant thereof. In some embodiments, the vaccine composition comprises: (a) a first peptide comprising SEQ ID NO:25 or a variant thereof; (b) a second peptide comprising SEQ ID NO:26 or a variant thereof; (c) a third peptide comprising SEQ ID NO:27 or a variant thereof; and (d) a fourth peptide comprising SEQ ID NO:28 or a variant thereof. In some embodiments, the vaccine composition comprises (a) a first peptide comprising SEQ ID NO:25 or a variant thereof; (b) a second peptide comprising SEQ ID NO:26 or a variant thereof; (c) a third peptide comprising SEQ ID NO:27 or a variant thereof; and (d) a fourth peptide comprising SEQ ID NO:28 or a variant thereof, wherein these four peptides are the only labyrinthin-derived peptides in the vaccine composition. In some embodiments, the labyrinthin-derived peptide is 21 to 24 amino acids in length, for example 22 or 23 amino acids in length. In some embodiments, the vaccine composition comprising a peptide comprising SEQ ID NO:25 or a variant thereof comprises SEQ ID NO:29 or a variant thereof. In some embodiments, the vaccine composition comprising a peptide comprising SEQ ID NO:26 or a variant thereof comprises SEQ ID NO:30 or a variant thereof. In some embodiments, the vaccine composition comprising a peptide comprising SEQ ID NO:27 or a variant thereof comprises SEQ ID NO:31 or a variant thereof. In some embodiments, the vaccine composition comprising a peptide comprising SEQ ID NO:28 or a variant thereof comprises SEQ ID NO:32 or a variant thereof.In some embodiments, the vaccine composition comprises (a) a first peptide comprising SEQ ID NO:29 or a variant thereof; (b) a second peptide comprising SEQ ID NO:30 or a variant thereof; (c) a third peptide comprising SEQ ID NO:31 or a variant thereof; and (d) a fourth peptide comprising SEQ ID NO:32 or a variant thereof, wherein these four peptides are the only labyrinthin-derived peptides in the vaccine composition. In some embodiments, the labyrinthin-derived peptide comprises a T cell epitope and / or a B cell epitope. In some embodiments, the effective amount of the antigenic composition in the vaccine composition is between about 0.1 μg and about 1000 μg, such as between about 75 μg and about 150 μg, such as about 100 μg. In some embodiments, the vaccine composition comprises GM-CSF. In some embodiments, the vaccine composition is LabVax 3(22)-23.
[0175] The methods disclosed herein are useful for treating or preventing a proliferative disease, such as cancer, in an individual. In some embodiments, the cancer is a labyrinthin-expressing cancer. In some embodiments, the cancer is an adenocarcinoma.
[0176] In some embodiments, the cancer is an early stage cancer, a non-metastatic cancer, a primary cancer, an advanced cancer, a locally advanced cancer, a metastatic cancer, a cancer in remission, a recurrent cancer, a resistant cancer, or a refractory cancer. In some embodiments, the cancer is a localized resectable cancer (e.g., a tumor limited to a part of an organ that allows complete surgical removal), a localized unresectable cancer (e.g., a localized tumor that is unresectable due to important vasculature), or an unresectable cancer. In some embodiments, the cancer is a stage I tumor, a stage II tumor, a stage III tumor, a stage IV tumor, an N1 tumor, or an M1 tumor according to the TNM classification.
[0177] The methods disclosed herein are useful for treating or preventing cancer, such as Labyrinthin-expressing cancer, in an individual. In some embodiments, the individual has one or more of the following characteristics: (i) the ability and willingness to understand and sign an informed consent form; (ii) at least 18 years of age with histologically confirmed adenocarcinoma and / or Labyrinthin-expressing cancer; (iii) previously treated with at least one systemic therapy (chemotherapy and / or biotherapy) and either did not respond / progressed during treatment, progressed after completion of systemic therapy, or refused all other treatments; (iv) the tumor overexpresses Labyrinthin antigen, as determined by immunohistochemical evaluation screening of paraffin-embedded archival specimens, and has a ≥10% IL-16 expression level at an intensity of at least 2× background as scored by a single reference pathologist. Malignant cells must show staining for antigen; (v) prior radiation therapy must have been completed at least 3 weeks prior to the first vaccine injection; (vi) any number of prior chemotherapy regimens; (vii) documentation of delayed type hypersensitivity (DTH) response to common recall antigens prior to the first vaccine injection; (viii) performance status of ≥ 60% on the Karnofsky scale; (ix) life expectancy at the time of the first vaccine injection ≥ 6 months; (x) measurable or evaluable disease; (xi) pretreatment absolute granulocyte count (AGC) ≥ 1000 and pretreatment platelet count ≥ 75000 obtained within 4 weeks prior to the first vaccine injection; (xii) pretreatment serum creatinine ≤ 1.5 mg / dL is required. Measurements must be obtained within 4 weeks prior to the first vaccine injection; and (xiii) serum bilirubin ≤ 1.5 and AST ≤ 2.5 x institutional upper limit of normal (≤ 5 x for liver metastases) obtained within 4 weeks prior to the first vaccine injection.
[0178] [Method of producing antibodies] The present disclosure, in some aspects, provides methods of generating antibodies in vivo, e.g., in a host animal. In some embodiments, the methods include administering to the host animal an antigenic composition disclosed herein. In some embodiments, the methods include administering to the host animal a nucleic acid composition disclosed herein. In some embodiments, the methods include administering to the host animal a vaccine composition disclosed herein.
[0179] Methods for producing antibodies in host animals are known, see, e.g., Lee, BS et al., Methods Mol Biol, 1474, 2016, 25-47.
[0180] In some embodiments, the labyrinthin-derived peptide is conjugated to a carrier, such as a protein. In some embodiments, the labyrinthin-derived peptide is conjugated to an albumin, such as bovine serum albumin. In some embodiments, the labyrinthin-derived peptide is conjugated to keyhole limpet hemocyanin (KLH).
[0181] In some embodiments, the antibody is a polyclonal antibody. In some embodiments, the antibody is a monoclonal antibody.
[0182] In some embodiments, the method of producing an antibody further comprises purifying the antibody.
[0183] Those skilled in the art will recognize that several embodiments are possible within the scope and spirit of the disclosure of this application. The disclosure is further illustrated by the following examples, which should not be construed as limiting the disclosure in scope or spirit to the specific procedures described therein. EXAMPLES
[0184] Example 1 This example demonstrates the design, synthesis, and selection formulation of Labyrinthin-derived peptides according to the present disclosure.
[0185] [Peptides designed for B and T cell immune responses] Labyrinthin-derived peptides were designed to generate B-cell and T-cell adaptive immune system responses. Using the labyrinthin amino acid sequence (SEQ ID NO:1) as a starting template, 13 labyrinthin-derived peptides were designed, and four labyrinthin-derived peptide candidates were selected for further evaluation and development (SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, and SEQ ID NO:32). The four selected labyrinthin-derived peptide candidates contain amino acid sequences with known immunogenicity via the B-cell adaptive immune system, and studies were performed to confirm that predicted binding to the MHCII complex groove also triggers a T-cell adaptive immune system response.
[0186] The solubility of four Labyrinthin-derived peptide candidates was tested in silico with the aim of identifying peptide candidates suitable for formulation and administration. For example, the water solubility of the Labyrinthin-derived peptide candidates was calculated using the Peptide Property Calculator (<http: / / www.pepcalc.com / > ) were used. All of the Labyrinthin-derived peptide candidates were confirmed to have good water solubility.
[0187] [Synthesis of Labyrinthin-derived peptides] Four labyrinthin-derived peptide candidates (SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, and SEQ ID NO: 32) were synthesized. Each labyrinthin-derived peptide candidate sequence was confirmed using mass spectrometry. Specifically, electrospray ionization mass spectrometry was used to obtain parent ion m / z spectra for each sample (spectra for SEQ ID NO: 29-32 are shown in Figures 1A-1D, respectively), and then tandem mass spectrometry was used to collect ion fragmentation data and confirm the peptide sequence of each labyrinthin-derived peptide candidate (data not shown).
[0188] The purity of each Labyrinthin-derived peptide candidate was determined using a high performance liquid chromatography technique that measures absorbance at 220 nm. The purity determined for each Labyrinthin-derived peptide candidate is shown in Table 3. JPEG2025072379000004.jpg42154
[0189] [Solubility and formulation of Labyrinthin-derived peptides] The solubility of each Labyrinthin-derived peptide candidate was assessed by visual inspection in ultrapure water, 0.1 M PBS (PBS; pH 7.4), and dimethyl sulfoxide (DMSO; analytical grade). Solubility below 0.1 mg / mL solvent was defined as "undissolved" and solubility above 0.1 mg / mL was defined as "dissolved," as reported in Table 4. The concentration range of measured solubility is provided under the "dissolved" classification when available (Table 4). JPEG2025072379000005.jpg57164
[0190] As observed, SEQ ID NO:30, SEQ ID NO:31, and SEQ ID NO:32 were not soluble in ultrapure water, which contradicts the predicted in silico solubility assessment above. Formulation in pH buffer (PBS, pH 7.4) did not improve the solubility of SEQ ID NO:31 and SEQ ID NO:32.
[0191] In an attempt to overcome the solubility issues identified above, additional testing was completed. The results of solubility testing performed on each of the Labyrinthin-derived peptide candidates (SEQ ID NOs:29-32) are shown in Table 5. In summary, all peptides were again soluble in DMSO, confirming the peptides' ability to dissolve in solution. Peptide solubility was then tested in normal saline (0.154 M sodium (NaCl)) and 0.2 M sodium (NaCl). Normal saline is generally the solvent / diluent of choice as it is accepted for use for such purposes by the Food and Drug Administration. SEQ ID NOs:31 and 32 did not dissolve in normal saline. Additional solutions were tested to determine alternative diluents to solubilize the candidate peptides as determined by visual inspection. As shown in Table 5, all four candidate peptides were soluble in 0.2 M saline. JPEG2025072379000006.jpg41170
[0192] In further solubility testing, two tubes of 1.1 mg peptide for each of the four candidate peptide targets were dissolved in 1 mL of phosphate buffer (pH 10) with and without 0.9% NaCl. After testing the solubility, the pH was successively adjusted with 2% acetic acid to lower the pH to the values shown in Table 6. The peptide solutions were then stored at 4° C. for several hours to allow complete peptide dissolution. After centrifugation, the peptide concentration remaining in the solution was measured. The solubility (mg / mL) of each peptide candidate for each condition is shown in Table 6. The solubility of all four peptide candidates was greater than 0.3 mg / mL under all test conditions in Table 6, with minimal variation in solubility across the pH range tested for each peptide candidate. JPEG2025072379000007.jpg119170
[0193] Each combination of the four peptides (SEQ ID NO:29-32) was diluted in either water (pH of about 6.7-7) or Isolyte (pH 7.4) and analyzed by an ultra-performance liquid chromatography (UPLC) method developed to analyze peptides in solution for vaccination. As shown in Figure 2, the numbers 1-4 correspond sequentially to the peptides of SEQ ID NO:29-32.
[0194] Each peptide has a very low pI, and the results shown in Figure 2 indicate that buffering to physiological levels led to the detection of doublets in all four peptides. The doublets were particularly prominent for peptides #1 (SEQ ID NO:29) and #2 (SEQ ID NO:30). Further dilution of the peptides reconstituted in Isolyte with water, as designed for each peptide, resulted in the UPLC traces of each peptide becoming a single peak (data not provided), as observed for the peptides reconstituted in water in Figure 2. This data indicates that (1) the peptides become charged due to being in an environment several pH units above their acidic pI, and (2) the peptide structure remains intact, as evidenced by each peptide becoming a single peak and returning to its original retention time (back to a more acidic pH) upon serial dilution with water.
[0195] Example 2 This example demonstrates the inhibition of tumor growth by a vaccine (LabVax 3(22)-23) containing four Labyrinthin-derived peptides (SEQ ID NOs:29-32).
[0196] C57BL / 6hPD-1 / PD-L1 mice implanted subcutaneously with MC38 murine colon (adenocarcinoma) tumor cells were administered either (a) 40 μg of LabVax (10 μg of each peptide, intradermal) in combination with murine GM-CSF (1 μg, subcutaneous) as adjuvant; or (b) saline control on days 15, 26, and 40 post-tumor implantation. Body weights and tumor weights were measured throughout the study. Statistical analysis of mouse body weights and tumor weights are shown in Table 7. JPEG2025072379000008.jpg35170
[0197] Body weights did not differ between vaccine versus saline control groups over the course of the study, and no adverse events were observed in either group. Results show that the vaccine caused a significant reduction in tumor growth (Figure 3), thus indicating that LabVax3(22)-23 has antitumor activity in the absence of toxicity in immunocompetent mice.
[0198] The safety results are consistent with a formal study conducted under good laboratory practice in Balb / C mice (Comparative Biosciences, Inc.; Sunnyvale, CA), in which no toxicity was observed with either the individual peptides or the combination [LabVax]3(22)-23] after five injections (50 μg of each peptide) over a 49-day period.
[0199] In addition, studies in seroconverted mice are consistent with the finding that use of the peptide is safe. Preclinical acute (2 injections over 14 days) and long-term (4 injections over 49 days) studies of LabVax3(22)-23 in mice were conducted under approved GLP animal testing. Dosage was approximately equivalent to approximately 120 times the intended human dosage (400 μg per injection). No clinically observed adverse events or abnormalities were noted across the four injections.
[0200] Example 3 To test for the production of antibodies following administration of the peptides described herein, 12 Balb / c mice were divided into 4 treatment groups, with each treatment group assigned to receive one injection of SEQ ID NOs: 29-32. Positive clones were identified in each treatment group, as shown in Table 8. JPEG2025072379000009.jpg48144
[0201] Example 4 This example demonstrates a Phase I trial of a four-peptide labyrinthin cancer vaccine (LabVax3(22)-23) in patients with adenocarcinoma. The four peptides of the vaccine are SEQ ID NOs:29-32.
[0202] Patients (12) selected for the Phase I study have inoperable or metastatic solid tumors (adenocarcinoma) that have failed standard treatment. Two treatment cohorts will be established based on: Cohort A: 6 patients will receive (intradermal) LabVax3(22)-23 alone; and Cohort B: 6 patients will receive (intradermal) LabVax3(22)-23 + GM-CSF (adjuvant). If there is an expansion of Phase I, the following will be included: 7 patients with breast adenocarcinoma; 7 patients with lung adenocarcinoma; 10 patients with other adenocarcinomas that are labyrinthin positive. All MCA44-3A6 positive (mouse monoclonal anti-labyrinthin antibody) adenocarcinomas will be included in each cohort of the expanded study segment.
[0203] The primary goal of this study is to demonstrate that the synthetic four-peptide cancer vaccine causes no short-term adverse effects in humans.
[0204] The secondary objectives of this study are: (i) to compare the safety of the vaccine with and without GM-CSF (adjuvant); (ii) to obtain a preliminary evaluation of the efficacy of the vaccine with and without GM-CSF (adjuvant); (iii) to compare the safety of the vaccine (with or without GM-CSF) in more specific areas of labyrinthin-positive breast and lung patients, as well as in cohorts of other labyrinthin-positive adenocarcinomas; and (iv) to obtain a preliminary evaluation of the vaccine (with or without GM-CSF) in more specific areas of labyrinthin-positive breast and lung patients, as well as in cohorts of other labyrinthin-positive adenocarcinomas.
[0205] Formulation, bottling, QA, QC, sterility testing, and labeling will be performed under cGMP. Further QA / QC stability testing will be performed at Emery Pharma. The peptides will be reconstituted in Isolyte S pH 7.4 to a concentration of 400 μg / 100 μl (containing 100 μg of each of the four peptides) and sterile filtered. The final product has a pH of approximately 6.5-7. The vaccine will then be dispensed into vials for clinical use and stored at -80°C. Ongoing studies have demonstrated that peptides can be made in this manner and reconstituted without any impact on the structural integrity of the peptides (by GLP-certified UPLC analysis; Emery Pharma, Alameda, CA).
[0206] For example, a computer-based analysis of four peptides was performed by SafaBridge Countarts (New York, NY and Mountain View, CA) and achieved an Occupational Health Categorization score of 2 out of category 4. This score indicates that the peptides are safe and that the score was only underestimated due to the lack of data available in the literature.
[0207] In cohort B, 100 mcg of human GM-CSF will be administered subcutaneously 45-60 minutes prior to the LabVax 3(22)-23 (intradermal) injection. GM-CSF will be injected using a 28-gauge needle within 3 cm of the vaccine injection site.
[0208] With a focus on breast and non-small cell lung cancers that are incurable with available therapies, subjects with advanced / metastatic or recurrent adenocarcinoma (Stage IV) of any primary site will be recruited from the UC Davis Comprehensive Cancer Center for Cohort A and Cohort B. A follow-up Phase I expansion will be opened to earlier stage adenocarcinoma subjects with labyrinthin-positive tumors.
[0209] Patients must meet all of the following criteria to be eligible for clinical study entry: (i) ability and willingness to understand and sign an informed consent form; (ii) patients at least 18 years of age with histologically confirmed adenocarcinoma; (iii) patients have been previously treated with at least one prior systemic therapy (chemotherapy and / or biologic therapy) and have failed / progressed during treatment, progressed after completion of systemic therapy, or refused all other treatment; (iv) tumors must overexpress labyrinthin antigen as determined by immunohistochemical evaluation screening of paraffin-embedded archival specimens, with >10% of malignant cells staining for the antigen at an intensity of at least 2× background as scored by a single reference pathologist; (v) prior radiation therapy must have been completed at least 3 weeks prior to the first vaccine injection. Patients must not have plans to receive concomitant radiation therapy to measurable disease. Measurable disease may be in the area of prior radiation if CT scan demonstrates that the disease is progressing or stable; (vi) any number of prior chemotherapy regimens are permitted. Prior chemotherapy must have been completed at least 3 weeks prior to the first vaccine injection, and patients must have recovered from all toxicities of previous treatments prior to the first vaccine injection; (vii) patients must have documented delayed-type hypersensitivity (DTH) responses to common recall antigens prior to the first vaccine injection. As part of the prescreening evaluation, patients undergo DTH testing to at least one common recall antigen; screening is at the physician's discretion based on medical history and physical characteristics (mumps, tinea, candida antigens, influenza matrix, and / or PPD, etc.). Skin tests are read at or about 48 hours. A skin response is considered positive if there is any measurable induration with erythema of 10 mm or greater.Erythema alone is not considered a positive DTH response;(viii) all patients must have a Karnofsky performance status of ≥ 60%;(ix) all patients must have a life expectancy of ≥ 6 months at the time of the first vaccine injection;(x) all laboratory work and all radiological studies (e.g., X-ray, CT) must be performed within 4 weeks prior to the first vaccine injection;(xi) patients must have measurable or evaluable disease (see Section 10). All patients must have a pretreatment absolute granulocyte count (AGC) ≥ 1000 and a pretreatment platelet count ≥ 75000 obtained within 4 weeks prior to the first vaccine injection;(xii) a pretreatment serum creatinine of ≤ 1.5 mg / dl is required. Measurements must be obtained within 4 weeks prior to the first vaccine injection;(xiii) patients must have serum bilirubin ≦1.5 and AST ≦2.5× institutional upper limit of normal (≦5× in case of liver metastases) obtained within 4 weeks prior to the first vaccine injection;(xiv) patients with known brain and / or leptomeningeal metastases are excluded because of the relatively short life expectancy that precludes evaluation of the activity and toxicity of this vaccine;and (xv) pregnant and lactating women are ineligible because the effect of the vaccine on the fetus or lactating infant is unknown. Women of childbearing age must have a negative urine or serum pregnancy test (HCG).
[0210] Patients who meet any of the following criteria will be excluded from clinical study entry: (i) known active immune disease, autoimmune disease, genetic or congenital immune deficiency, underlying immune deficiency, or altered immune function (e.g., active Graves' disease, AIDS / HIV, Addison's disease, myasthenia gravis, severe atopic dermatitis, rheumatoid arthritis, eczema-scleroderma, Goodpasture's syndrome, Sjogren's syndrome, ankylosing spondylitis, Hashimoto's thyroiditis, systemic lupus erythematosus, autoimmune neutropenia / thrombocytopenia, immune-mediated hemolytic anemia, or a history of anaphylaxis requiring ICU care). Please contact the investigator for clarification regarding this criterion; (ii) patients who have had a previous splenectomy are ineligible due to immunocompromise; (iii) pregnant or lactating women; (iv) any medical condition, including additional malignancy, laboratory abnormality, or psychiatric illness, that would prevent the subject from participating in and complying with study-related procedures; (v) an uncontrolled intercurrent illness that, in the investigator's opinion, would interfere with the patient's safety or compliance in the study; and (vi) a severe infection within 4 weeks prior to enrollment that, in the investigator's opinion, would interfere with the patient's safety or compliance in the study.
[0211] Dose-limiting toxicity (DLT) in a given patient is defined as grade III non-hematologic toxicity not reversible to grade II or less within 96 hours, or grade IV toxicity. DLT is based on the first course of treatment. Toxicity is graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE; version 5.0). To be evaluable for toxicity, patients must have received at least one complete course of treatment and been observed for at least 6 months after the start of the first course or have experienced a DLT. All patients not evaluable for toxicity are replaced.
[0212] The maximum tolerated dose (MTD) is defined as the highest dose tested at which <33% of patients experienced a DLT due to study drug (LabVax3(22)-23 ± adjuvant) when at least 6 patients were treated at that dose and evaluable for toxicity. The MTD is one injection level below the lowest dose tested at which ≥33% of patients experienced a DLT due to study drug. At least 6 patients are treated at the MTD.
[0213] The DLT level is the lowest injection level tested at which 33% or more patients experienced a DLT attributable to study drug. The DLT level is one dose level above the MTD.
[0214] Six patients for each vaccine / vaccine+GM-CSF group are treated at scheduled intervals from 5 to 12 weeks. If 0 / 3 of the first patients in each group experience a DLT after the first two injections, the next 3 patients are enrolled while the first group continues the injection schedule. If a DLT due to the study drug is experienced in exactly 1 / 3 of the patients, 3 more patients (6 in total) are treated up to that injection series volume. If no further DLTs are observed with the expanded injection schedule (i.e., 1 / 6 or less with DLTs), the injection regimen is continued. Injections are terminated as soon as 2 or more patients experience a DLT due to the study drug at a given injection frequency. When 6 patients in each group are treated and a maximum of 1 / 6 patients experience a DLT, the Phase I study is terminated. If more than 1 / 6 patients experience a DLT, the next smaller volume of injections is used for the remaining patients.
[0215] All patients who have not experienced a DLT in the preceding interval will continue with the next injection as needed. If no DLT is observed and benefit is observed, treatment will continue in the individual patient according to the injection schedule; patients will discontinue treatment in the event of unacceptable toxicity (as determined by the treating physician and / or patient) or toxicity requiring discontinuation of treatment.
[0216] Based on the first-in-human clinical trials, after patients complete the 12-week injection schedule and one-month follow-up phase, patients with stable disease or tumor regression are taken off-study and given additional vaccinations (e.g., boosters, to initiate patient seroconversion). The treating physician will determine the frequency of injections.
[0217] All patients eligible for this trial will be prescreened prior to protocol therapy to determine that their tumors overexpress the Labyrinthin antigen, as determined by immunohistochemistry evaluation screening of paraffin-embedded archival specimens demonstrating that >10% of malignant cells stain for the antigen. One affiliated pathologist will perform this evaluation.
[0218] This is a single-center, open-label study of the synthetic peptide cancer vaccine LabVax3(22)-23, aimed at generating an immune response against tumor-associated antigens. The study design is to investigate the safety of the vaccine (± GM-CSF adjuvant) in a pilot group of patients with adenocarcinoma. Preliminary information on efficacy will be obtained and post-study correlations on seroconversion will be made.
[0219] Vials are provided containing enough peptide vaccine to achieve an injection of 400 μg / 100 μl (100 μg of each of the four peptides) diluted in Isolyte S (pH 7.4). GM-CSF (250 μg / vial) is used according to the manufacturer's information. A co-dose of 100 μg is given with each injection of LabVax3(22)-23.
[0220] Patients will receive 400 μg of peptide vaccine in a total volume of 0.1 ml intradermally at weeks 1, 2, 4, 8, and 12 (booster vaccinations at weeks 24 and 36 pending clinical response). Vaccine will be stored at -20°C and warmed to room temperature before use. Vaccine should be used within 1 hour of reaching room temperature.
[0221] Using a 1 ml syringe with a 28 gauge needle or smaller, 0.1 ml is aspirated from a single vial. The total volume is injected intradermally after 60% of the needle's length (approximately 4 mm) has been passed through the dermis.
[0222] After the fluid has been injected, the needle / syringe should be held in place for 5 minutes (may be taped in place) to prevent backflow. A patch is applied to the injection site to prevent pressure being applied to the injected fluid. Patients are advised not to apply pressure to the injection site until the fluid is absorbed. Sterile saline is used to reconstitute and administer within 1 hour of vaccination to achieve the equivalent of a simultaneous administration of 100 μg GM-CSF (when used). If necessary, an alternate injection site will be determined, either on the leg or abdomen. It is intended that each vaccination in the series will be administered at a slightly different site (3 cm from the last injection site if the previous injection site is visible) and the relative location will be recorded. Any inflammation at the site will be documented (photographs and / or written records). Inflammation is defined as an area of persistent redness and / or induration of more than 20 mm around the injection site lasting more than one week or any skin ulceration.
[0223] The first three patients from each group (± GM-CSF) are observed for 60 minutes post-immunization for the first five immunizations. Temperature, vital signs, and responses are assessed by staff every 15 minutes at the end of the post-immunization period. Patients have their temperature taken and recorded that same evening (and an additional hour if they have symptoms of fever) and record any other symptoms they feel. If patients report skin lesions, they are asked to come in for evaluation. If no serious adverse reactions are seen in the first six patients with the first five doses, the observation time is waived for the remaining injections. Patients 7-12 are monitored for 60 minutes immediately after their first vaccine injection. Subsequent injections do not require post-vaccination observation unless clinically indicated.
[0224] Serum samples will be collected at weeks 0, 1, 2, 4, 8, 12, and 14 (or within 10-20 days after the last injection, if there is a booster vaccine injection) to assess post-study seroconversion, and will also be available to check for any systemic toxicity, if necessary. Serum samples will be collected immediately prior to each vaccination.
[0225] Up to three patients will be enrolled each week until the first six patients have received five doses without adverse events (grade >2).
[0226] If intradermal injection results in skin ulceration, subsequent injections may be administered subcutaneously for the remainder of the vaccination. Because the vaccination is administered intradermally (intradermally), if the patient exhibits a significant immune response, the DTH response will preclude further intradermal administration. A significant DTH response is defined as persistent redness and induration of more than 20 mm around the injection site or any skin ulceration lasting more than one week.
[0227] Subjects will be evaluated for 31 weeks, including a 4-week follow-up examination after the last injection (or the last injection if injections are stopped earlier), after which subjects will be evaluated for immunological parameters at 4 and 7 months after the last injection.
[0228] Patients may receive ongoing symptomatic and palliative treatment (e.g., nutritional support, pain management) as clinically indicated throughout the study. Patients may not be receiving any concurrent oncological or cancer-directed treatment (e.g., chemotherapy, biologic therapy, etc.). Bisphosphonate therapy is permitted as part of the symptomatic treatment. Patients who develop emergent complications at sites of previously documented disease may receive palliative radiation therapy. Continuation of protocol therapy, if medically appropriate, will be determined in discussion with the sponsor and investigator.
[0229] Patients will be removed from protocol treatment if any of the following conditions are met: (i) unacceptable toxicity (as determined by the treating physician and / or the patient) or toxicity requiring discontinuation of treatment; (ii) patients may choose to withdraw from the study at any time for any reason; (iii) patients may be withdrawn from the protocol at the investigator's discretion if the investigator feels that continuation is not in the patient's best medical interest or if the patient's compliance with treatment is poor; (iv) disease progression characterized by the development of new lesions or if existing disease increases by more than 100% of the longest linear diameter of baseline or nadir (whichever is less); (v) disease progression according to RECIST (Response Evaluation Criteria in Solid Tumors) criteria; and (vi) completion of protocol therapy as follows: (a) completion of five scheduled vaccinations; and (b) final dose of the 12th patient (Phase I) or 30th patient (Phase I expansion segment). Patients who initiate but do not complete the full injection schedule of a given cohort will not be counted in the total number of patients required to complete each respective cohort; their data will be included in the study summaries.
[0230] If a patient does not respond to protocol treatment and / or is discontinued due to toxic effects or "disease progression," further treatment, if any, will be at the discretion of the investigator.
[0231] After removal from protocol treatment, all patients will be followed for late toxicity. Patients will be seen 4, 12, and 28 weeks after stopping treatment (last injection). If ongoing toxicity does not resolve to ≦Grade 1 within the first 4 weeks, patients will be seen monthly until toxicity resolves to ≦Grade 1. New toxicities after 4 weeks of follow-up will not be reported unless deemed related to the treatment protocol by the investigator. A final report is required for all patients after final follow-up or upon death.
[0232] Patients will be enrolled in the study as outlined above. If at any time during the study there is sufficient evidence to suggest an excessive toxicity grade of grade 3 or grade 4, the study will be terminated. An excessive grade 3 toxicity grade will be assigned to 20% (or 4 patients) of the patients enrolled on that day, and an excessive grade 4 toxicity grade will be assigned to 10% (or 2 patients). If the lower limit of the 90% one-sided confidence interval of the estimated toxicity grade exceeds the appropriate limit (20% for grade 3, 10% for grade 4), the evidence of an excessive toxicity grade will be considered sufficient.
[0233] Operationally, this occurs when any of the following occurs: (i) grade 3 toxicity (n=20): 2 of the first 2 patients, 3 of the first 6 patients, 4 of the first 9 patients, 5 of the first 13 patients, 6 of the first 14 patients, or 7 of the first 19 patients; or (ii) grade 4 toxicity (n=20): 2 of the first 5 patients, 3 of the first 11 patients, 4 of the first 18 patients, or 5 of the first 19 patients.
[0234] The toxicity scale, definitions, and specific criteria for each toxicity level are those outlined in the guidelines defined by CTCAE version 3.0. If a patient develops grade 3 or higher hematologic or non-hematologic toxicity that is probably, probably, or definitely related to immunization, the patient will not receive further vaccinations and will be removed from protocol therapy. No changes in vaccine dose will be permitted. If the observed grade ≥ 3 toxicity is determined by the investigator to be related to the immune response generated, a corticosteroid regimen will be administered.
[0235] A comprehensive metabolic panel will be performed on serum (including total bilirubin, SGOT, and creatinine) and monitored at weeks 0, 1, 2, 4, 8, and 12; and at any additional vaccination weeks (i.e., weeks 24 and 36) if deemed necessary according to the schema. In addition, patients will undergo a physical examination at the time of the first immunization and then each vaccination. Patients will be observed for the development of autoimmunity in normal tissues that may express basal levels of labyrinthin, particularly in the skin and salivary glands.
[0236] Baseline evaluation should be performed up to 14 days prior to the first vaccine injection unless otherwise noted. Scans and x-rays should be performed up to 28 days prior to the first vaccine injection. If the patient's condition worsens, laboratory evaluation should be repeated up to 48 hours prior to starting the next treatment cycle. JPEG2025072379000010.jpg175170
[0237] Unless otherwise specified, within 4 weeks prior to the first vaccine injection: (i) medical history and physical examination including height, weight, performance status, clinical oncology measurements; (ii) hematology: complete blood count with automated differential; (iii) biochemistry: serum creatinine, AST, total bilirubin; and (iv) radiology: scans / x-rays as needed to document disease (within 3 months prior to the first vaccine injection). To ensure comparability, baseline x-rays / scans and subsequent x-rays / scans to assess response should be performed using the same technique; i.e., scans are performed immediately after bolus contrast administration using standard contrast volume, the same contrast agent, and preferably the same scanner.
[0238] Other investigations include: (i) baseline serum sample (for antibody titers); (ii) pregnancy test (for women of childbearing potential) within 2 weeks prior to the first vaccine injection; (iii) DTH to common recall antigens within 3 months prior to the first vaccine injection; (iv) immunohistochemistry (tumor tissue must be positive for labyrinthin expression for eligibility) should be performed within 3 months prior to the first vaccine injection.
[0239] All patients are evaluable for toxicity from the time of their first treatment with LabVax 3(22)-23. All patients are evaluable for toxicity from peptide injections and will be monitored for acute toxicity. All patients will be monitored by a attending physician for 1 hour post-injection and for the first 3 injections.
[0240] Response and progression will be assessed in this study using the new international criteria proposed by the RECIST (Response Evaluation Criteria in Solid Tumors) committee. Changes in only the maximum diameter (unidimensional measurement) of tumor lesions are used in the RECIST criteria.
[0241] A measurable lesion is defined as one that can be accurately measured in at least one dimension (longest diameter recorded) as ≥ 20 mm by common techniques (PE, CT, XR, MRI) or ≥ 10 mm by spiral CT scan. All tumor measurements must be recorded in millimeters (or fractions of a centimeter).
[0242] All other lesions (or disease sites), including small lesions (<20 mm in longest diameter by common techniques or <10 mm by spiral CT scan), are considered non-measurable disease. Bone lesions, leptomeningeal disease, ascites, pleural / pericardial effusion, cutaneous lymphangitis / pneumonia, inflammatory zoonosis, abdominal masses (not seen by CT or MRI), and cystic lesions are all non-measurable. Patients with prostate cancer may also have PSA-only disease.
[0243] All measurable lesions, up to a maximum of 5 lesions per organ and 10 lesions total representing all involved organs, should be identified as target lesions and recorded and measured at baseline. Target lesions should be selected based on their size (lesion with longest diameter) and their suitability for accurate repeated measurement (imaging technique or clinical). The sum of the longest diameters (LD) for all target lesions is calculated and reported as the baseline sum LD. The baseline sum LD is used as a reference to further characterize the objective tumour response of measurable dimensions of disease. If there are >10 measurable lesions, those not selected as target lesions are considered non-target lesions along with non-measurable disease.
[0244] In addition to all non-measurable lesions (or disease sites), any measurable lesions greater than 10 listed as target lesions. Measurements are not required, but these lesions should be noted at baseline and tracked as "present" or "absent."
[0245] All patients will have their best response to the study classified as outlined below: Complete Response (CR): disappearance of all clinical and radiological evidence of tumor (both target and non-target); Partial Response (PR): at least a 30% decrease in the LD sum of target lesions, taking the baseline sum LD as reference; and Stable Disease (SD): steady state disease. Neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD; Progression (PD): at least a 20% increase in the LD sum of measured lesions, taking the smallest LD recorded since the start of treatment as reference, or the appearance of one or more new lesions. The appearance of new lesions also constitutes progression. In exceptional circumstances, evident progression of non-target lesions may be accepted as evidence of disease progression. In exceptional circumstances, evident progression of non-target lesions may be accepted as evidence of disease progression. JPEG2025072379000011.jpg125157
[0246] Duration of response will be measured from the time the CR / PR (whichever is first recorded) criterion is first met to the first date of objective documentation of recurrent or progressive disease. Stable disease duration will be measured from the start of treatment until progression criteria are met, using the smallest recorded measurement since the start of treatment as reference.
[0247] Clinical serological studies will be performed in all patients after the course of this study to evaluate any development of serum antibodies against the Labyrinthin-based peptides. Antibody responses will be measured and evaluated as total immunoglobulin (IgM, IgG, IgA, IgD, and IgE) responses against the Labyrinthin-based peptides (all four combined). Individual IgM and IgG responses will be measured for research purposes but will not be used to direct treatment in this study. IgG subclass responses will also be determined for research purposes and will not be used to direct treatment. These responses will be evaluated at weeks 4, 9, 12, 15, 19, 23, and 27.
[0248] A 10 ml blood sample is taken as outlined above. Each sample is collected in a non-heparinized vacutainer with a 20 g or larger needle. Blood samples are immediately chilled in wet ice (approximately 4-8°C) and kept at this temperature until processed to separate the serum. Sodium azide is added to the serum as a preservative (final concentration within 0.05-0.1% using a saturated sodium azide solution) and the amount added is recorded along with the total volume of serum. Samples should be divided equally and stored at -80°C in two different freezers until analysis.
[0249] Serum should never be frozen. Samples (10 cc) should be stored in their collection tubes (LabyRx provided; sodium azide, non-heparinized, red top tubes with wax phase separators) in a refrigerator (4°C). Serum samples will remain at the facility and will be shipped in bulk later during the study period. The serum reserve is a precaution against loss of sample during shipment or subsequent storage.
[0250] Patients who seroconvert at 1:100,000 are asked to provide 10 ml of whole blood for isolation of viable lymphoid cells (optional; one-time only). The whole blood is run through a Ficoll step gradient, the cells are washed three times with Hank's buffer, and the cells are aliquoted and cryopreserved (approximately 5 × 10 6 These cells will be provided to LabyRx (or a third party testing laboratory) for evaluation of cellular immune responses and other research-related testing.
[0251] Prior to patient treatment, formalin-fixed paraffin-embedded tissue containing a representative sample of tumor tissue must be submitted for immunohistochemical staining and detection / assessment of labyrinthin. SEQUENCE LISTING <110> LABYRX IMMUNOLOGIC THERAPEUTICS (USA) LIMITED <120> LABYRINTHIN-BASED PEPTIDES FOR CANCER IMMUNOTHERAPIES AND USES THEREOF <130> 18572-20001.40 <140> Not Yet Assigned <141> Concurrently Herewith <150> US 62 / 779,377 <151> 2018-12-13 <160> 32 <170> FastSEQ for Windows Version 4.0 <210> 1 <211> 255 <212> PRT <213> Homo sapiens <400> 1 Met Val Ile Ala Leu Leu Gly Val Trp Thr Ser Val Ala Val Val Trp 1 5 10 15 Phe Asp Leu Val Asp Tyr Glu Glu Val Leu Gly Lys Leu Gly Ile Tyr 20 25 30 Asp Ala Asp Gly Asp Gly Asp Phe Asp Val Asp Asp Ala Lys Val Leu 35 40 45 Leu Gly Leu Lys Glu Arg Ser Thr Ser Glu Pro Ala Val Pro Pro Glu 50 55 60 Glu Ala Glu Pro His Thr Glu Pro Glu Glu Gln Val Pro Val Glu Ala 65 70 75 80 Glu Pro Gln Asn Ile Glu Asp Glu Ala Lys Glu Gln Ile Gln Ser Leu 85 90 95 Leu His Glu Met Val His Ala Glu His Val Glu Gly Glu Asp Leu Gln 100 105 110 Gln Glu Asp Gly Pro Thr Gly Glu Pro Gln Gln Glu Asp Asp Glu Phe 115 120 125 Leu Met Ala Thr Asp Val Asp Asp Arg Phe Glu Thr Leu Glu Pro Glu 130 135 140 Val Ser His Glu Glu Thr Glu His Ser Tyr His Val Glu Glu Thr Val 145 150 155 160 Ser Gln Asp Cys Asn Gln Asp Met Glu Glu Met Met Ser Glu Gln Glu 165 170 175 Asn Pro Asp Ser Ser Glu Pro Val Val Glu Asp Glu Arg Leu His His 180 185 190 Asp Thr Asp Asp Val Thr Tyr Gln Val Tyr Glu Glu Gln Ala Val Tyr 195 200 205 Glu Pro Leu Glu Asn Glu Gly Ile Glu Ile Thr Glu Val Thr Ala Pro 210 215 220 Pro Glu Asp Asn Pro Val Glu Asp Ser Gln Val Ile Val Glu Glu Val 225 230 235 240 Ser Ile Phe Pro Val Glu Glu Gln Gln Glu Val Pro Pro Asp Thr 245 250 255 <210> 2 <211> 3 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 2 Glu Pro Ala 1 <210> 3 <211> 4 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 3 Val Pro Pro Glu 1 <210> 4 <211> 3 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 4 Glu Pro His 1 <210> 5 <211> 3 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 5 Glu Pro Glu 1 <210> 6 <211> 3 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 6 Val Pro Val 1 <210> 7 <211> 3 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 7 Glu Pro Gln 1 <210> 8 <211> 3 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 8 Gly Pro Thr 1 <210> 9 <211> 3 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 9 Asn Pro Asp 1 <210> 10 <211> 3 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 10 Glu Pro Val 1 <210> 11 <211> 3 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 11 Glu Pro Leu 1 <210> 12 <211> 4 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 12 Ala Pro Pro Glu 1 <210> 13 <211> 3 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 13 Asn Pro Val 1 <210> 14 <211> 3 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 14 Phe Pro Val 1 <210> 15 <211> 4 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 15 Val Pro Pro Asp 1 <210> 16 <211> 7 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 16 Glu Pro Ala Val Pro Pro Glu 1 5 <210> 17 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 17 Val Pro Pro Glu Glu Ala Glu Pro His 1 5 <210> 18 <211> 7 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 18 Glu Pro His Thr Glu Pro Glu 1 5 <210> 19 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 19 Glu Pro Glu Glu Gln Val Pro Val 1 5 <210> 20 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 20 Val Pro Val Glu Ala Glu Pro Gln 1 5 <210> 21 <211> 7 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 21 Gly Pro Thr Gly Glu Pro Gln 1 5 <210> 22 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 22 Asn Pro Asp Ser Ser Glu Pro Val 1 5 <210> 23 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 23 Ala Pro Pro Glu Asp Asn Pro Val 1 5 <210> 24 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 24 Phe Pro Val Glu Glu Gln Gln Glu Val Pro Pro Asp 1 5 10 <210> 25 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 25 Asp Gly Pro Thr Gly Glu Pro Gln Gln Glu 1 5 10 <210> 26 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 26 Glu Gln Glu Asn Pro Asp Ser Ser Glu Pro Val 1 5 10 <210> 27 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 27 Ala Pro Pro Glu Asp Asn Pro Val Glu Asp 1 5 10 <210> 28 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 28 Glu Glu Gln Gln Glu Val Pro Pro Asp 1 5 <210> 29 <211> 22 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 29 Gly Glu Asp Leu Gln Gln Glu Asp Gly Pro Thr Gly Glu Pro Gln Gln 1 5 10 15 Glu Asp Asp Glu Phe Leu 20 <210> 30 <211> 22 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 30 Asp Met Glu Glu Met Met Ser Glu Gln Glu Asn Pro Asp Ser Ser Glu 1 5 10 15 Pro Val Val Glu Asp Glu 20 <210> 31 <211> 22 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 31 Asn Glu Gly Ile Glu Ile Thr Glu Val Thr Ala Pro Pro Glu Asp Asn 1 5 10 15 Pro Val Glu Asp Ser Gln 20 <210> 32 <211> 23 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 32 Asp Ser Gln Val Ile Val Glu Glu Val Ser Ile Phe Pro Val Glu Glu 1 5 10 15 Gln Gln Glu Val Pro Pro Asp 20
Claims
1. An antigenic composition comprising one or more labyrinthin-derived peptides, each labyrinthin-derived peptide comprising one or more T cell epitopes and B cell epitopes.
2. 2. The antigenic composition of claim 1, wherein each of the one or more labyrinthin-derived peptides comprises a T cell epitope and a B cell epitope.
3. 3. The antigenic composition of claim 1 or 2, wherein the one or more labyrinthin-derived peptides are 8 to 25 amino acids in length.
4. 4. The antigenic composition according to claim 1, wherein one or more labyrinthin-derived peptides are substantially homologous to a portion of labyrinthin.
5. 5. The antigenic composition of claim 1, wherein each of the one or more labyrinthin-derived peptides comprises a non-terminal proline residue.
6. (a) a first peptide comprising SEQ ID NO:25 or a variant thereof; (b) a second peptide comprising SEQ ID NO:26, or a variant thereof; (c) a third peptide comprising SEQ ID NO:27 or a variant thereof; and (d) a fourth peptide comprising SEQ ID NO:28 or a variant thereof. comprising one or more labyrinthin-derived peptides selected from the group consisting of one or more Labyrinthin-derived peptides are 12 to 25 amino acids in length; and An antigenic composition, wherein each peptide comprises a T cell epitope and a B cell epitope.
7. The antigenic composition of claim 6 , wherein the first peptide comprises SEQ ID NO:
25.
8. The antigenic composition of claim 6 or 7, wherein the second peptide comprises SEQ ID NO:
26.
9. The antigenic composition of any one of claims 6 to 8, wherein the third peptide comprises SEQ ID NO:
27.
10. 10. The antigenic composition of claim 6, wherein the fourth peptide comprises SEQ ID NO:
28.
11. 11. An antigenic composition according to any one of claims 6 to 10, wherein the one or more labyrinthin-derived peptides are 21 to 24 amino acids in length.
12. 12. The antigenic composition of claim 6, wherein the one or more labyrinthin-derived peptides are 22 or 23 amino acids in length.
13. 13. An antigenic composition according to any one of claims 6 to 12, wherein one or more labyrinthin-derived peptides are substantially homologous to a portion of labyrinthin.
14. 14. The antigenic composition of any one of claims 6 to 13, wherein the first peptide is SEQ ID NO:29 or a variant thereof having one or two amino acids substituted, deleted, inserted and / or added relative to SEQ ID NO:
29.
15. 15. The antigenic composition of any one of claims 6 to 14, wherein the first peptide is SEQ ID NO:
29.
16. 16. The antigenic composition of any one of claims 6 to 15, wherein the second peptide is SEQ ID NO:30 or a variant thereof having one or two amino acids substituted, deleted, inserted and / or added relative to SEQ ID NO:
30.
17. 17. The antigenic composition of any one of claims 6 to 16, wherein the second peptide is SEQ ID NO:
30.
18. 18. The antigenic composition of any one of claims 6 to 17, wherein the third peptide is SEQ ID NO:31 or a variant thereof having one or two amino acids substituted, deleted, inserted and / or added relative to SEQ ID NO:
31.
19. 19. The antigenic composition of any one of claims 6 to 18, wherein the third peptide is SEQ ID NO:
31.
20. 20. The antigenic composition of any one of claims 6 to 19, wherein the fourth peptide is SEQ ID NO: 32 or a variant thereof having one or two amino acids substituted, deleted, inserted and / or added relative to SEQ ID NO:
32.
21. 21. The antigenic composition of any one of claims 6 to 20, wherein the fourth peptide is SEQ ID NO:
32.
22. 22. An antigenic composition according to any one of claims 6 to 21, wherein at least one of the one or more labyrinthin-derived peptides is conjugated to a linker.
23. 23. An antigenic composition according to any one of claims 6 to 22, wherein the antigenic composition comprises two or more labyrinthin-derived peptides.
24. 24. The antigenic composition of claim 6, wherein the antigenic composition comprises three or more labyrinthin-derived peptides.
25. 25. The antigenic composition of any one of claims 6 to 24, wherein the antigenic composition comprises four labyrinthin-derived peptides.
26. 26. A nucleic acid composition comprising one or more nucleic acids encoding at least one of one or more labyrinthin-derived peptides comprised in the antigenic composition of any one of claims 1 to 25.
27. (a) an effective amount of an antigenic composition according to any one of claims 1 to 25; (b) a pharma- ceutically acceptable vehicle 20. A vaccine composition comprising:
28. 28. The vaccine composition of claim 27, wherein the pharma- ceutically acceptable vehicle is selected from the group consisting of an aqueous suspension, an oily suspension, an emulsion, a liposome, a virosome, and a nanoparticle.
29. 29. The vaccine composition of claim 27 or 28, wherein the pharma- ceutically acceptable vehicle comprises an additive.
30. 30. The vaccine composition of any one of claims 27 to 29, wherein the pharma- ceutically acceptable vehicle comprises an adjuvant.
31. 31. The vaccine composition of claim 30, wherein the adjuvant is an immune enhancing adjuvant.
32. 32. A method for treating cancer in an individual in need thereof, comprising administering to the individual a vaccine composition according to any one of claims 27 to 31.
33. 33. The method of claim 32, further comprising administering to the individual an immune checkpoint inhibitor.
34. A method for producing antibodies in a host animal, comprising administering to the host animal an antigenic composition described in any one of claims 1 to 25, a nucleic acid composition described in claim 26, or a vaccine composition described in any one of claims 27 to 33, thereby producing antibodies.