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US-12624093-B2 - Ehrlichia vaccines and immunogenic compositions

US12624093B2US 12624093 B2US12624093 B2US 12624093B2US-12624093-B2

Abstract

Provided herein are immunogenic compositions that may be used, in some aspects, to induce an immune response against an Ehrlichia such as Ehrlichia canis . In some embodiments, the immunogenic composition comprises an E. canis bacterin and/or adjuvant, such as for example an emulsion or liposomal adjuvant. Related methods such as for diagnosis of or vaccination against ehrlichiosis are also provided.

Inventors

  • Jere W. McBride
  • Paul J. Dominowski
  • Suman Mahan
  • Jason J. Millership
  • Duncan M. Mwangi
  • Sharath RAI
  • Sharon M. WAPPEL

Assignees

  • RESEARCH DEVELOPMENT FOUNDATION
  • ZOETIS SERVICES LLC

Dates

Publication Date
20260512
Application Date
20200713

Claims (7)

  1. 1 . An immunogenic composition comprising a suspension of an Ehrlichia canis bacterin and a combination of immunogenic tandem repeat proteins (TRP) consisting of isolated TRP36, TRP140 and TRP19 proteins of Ehrlichia canis , a pharmaceutically acceptable excipient, and an adjuvant formulation consisting of a purified or partially purified immunologically active saponin prepared from the bark of Quillaja saponaria , cholesterol, and a CpG-containing ODN, wherein the Ehrlichia canis bacterin is inactivated with binary ethyleneimine (BEI).
  2. 2 . The immunogenic composition of claim 1 , wherein the TRP19 protein comprises SEQ ID NO: 1, the TRP140 protein comprises SEQ ID NO: 14 and the TRP36 protein comprises one of SEQ ID NOs: 3 to 11.
  3. 3 . The immunogenic composition of claim 1 , wherein the TRP36 protein, the TRP140 protein and the TRP19 protein are produced recombinantly.
  4. 4 . The immunogenic composition of claim 1 , wherein the CpG-containing ODN is of SEQ ID NO: 17.
  5. 5 . The immunogenic composition of claim 1 , wherein the adjuvant formulation is an oil-in-water emulsion.
  6. 6 . A method of inducing an immune response in a mammalian subject comprising administering to the subject a pharmaceutically relevant amount of the immunogenic composition of claim 1 .
  7. 7 . The method of claim 6 , wherein the mammalian subject is a dog.

Description

This application is a national phase application under 35 U.S.C. § 371 of International Application No. PCT/US2020/041779, filed Jul. 13, 2020, which claims the benefit of United States Provisional Patent Application No. 62/873,843, filed Jul. 12, 2019, U.S. Provisional Patent Application No. 62/879,762, filed Jul. 29, 2019, and U.S. Provisional Patent Application No. 63/049,476, filed Jul. 8, 2020, the entirety of each of which is incorporated herein by reference. BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates generally to the field of molecular biology and medicine. More particularly, it concerns immunogenic or vaccine compositions against Ehrlichia canis and related methods. 2. Description of Related Art Human monocytotropic ehrlichiosis (HME) is a group 1 NIAID emerging disease, and the etiologic agent, Ehrlichia chaffeensis, is classified as a Category C priority pathogen. HME is an undifferentiated febrile illness that is life-threatening, clinical diagnosis is difficult, and definitive diagnosis is most often retrospective (Walker and Dumler, 1997; Walker et al., 2004; Dumler et al., 2007). Although well over 8,000 cases have been reported to the Centers for Disease Control as of 2012, this number likely underestimates the actual number of cases by 100-fold (Olano et al., 2003). The disease is often undiagnosed due to the non-specific symptoms associated with the onset, but it results in patient hospitalization in 43-62% of cases (Fishbein et al., 1994). Progression of the disease can result in a fatal outcome and often involves multisystem failure, with acute respiratory distress syndrome (ARDS) and meningoencephalitis being common in many fatal cases (Fishbein et al., 1994; Paparone et al., 1995). The threat to public health is increasing with newly emerging ehrlichial agents, yet vaccines for human ehrlichioses are not available, and therapeutic options are limited. Ehrlichia canis (E. canis) is a related organism that can infect dogs and causes similar veterinary and clinical problems. Clearly, there is a need for new and improved methods for diagnosing and vaccinating against Ehrlichia such as E. canis. SUMMARY OF THE INVENTION The present invention, in some aspects, overcomes limitations in the prior art by providing new compositions and methods that may be used to generate an immune response against Ehrlichia canis. In some embodiments, the composition contains at least two E. canis proteins or immunogenic peptides and an adjuvant, as described herein. Related methods for generating an immune response against E. canis are also provided. In some embodiments, an immune response can be induced in a mammalian subject (e.g., a dog) by administering to the subject: (i) an E. canis bacterin, (ii) an adjuvant (e.g., comprising Quil A, cholesterol, and an immunostimulatory oligonucleotide), and (iii) one or more TRP proteins or peptides, and these components may be administered in a single pharmaceutical composition (comprising the bacterin, the adjuvant, and the one or more TRP protein or peptides) or in multiple pharmaceutical compositions. For example, the subject may be administered both a first pharmaceutical composition (comprising the TRP protein(s) and the adjuvant), and a second pharmaceutical composition (comprising the bacterin and the adjuvant), wherein the first pharmaceutical composition and the second pharmaceutical composition are administered at substantially the same time or at different times. In some aspects, the invention relates to an immunogenic composition comprising: (i) at least 1, 2, 3, 4, 5, 6, or all of TRP153, TRP36, TRP140, TRP28, TRP95, TRP 19, and/or TRP120 (e.g., TRP140, TRP36, and/or TRP19); and at least 1, 2, 3, 4, 5, or more peptides comprising or consisting of a peptide of any one of SEQ ID NOs:1-16; (ii) at least 2, 3, 4, 5, 6, or all of TRP153, TRP36, TRP140, TRP28, TRP95, TRP19 and/or TRP120 (e.g., TRP140, TRP36, and/or TRP19); (iii) an E. canis bacterin and at least 1, 2, 3, 4, 5, 6, or all of TRP153, TRP36, TRP140, TRP28, TRP95, TRP19, or TRP120 (e.g., TRP140, TRP36, and/or TRP19); (iv) an E. canis bacterin and at least 1, 2, 3, 4, 5, or more peptides comprising or consisting of a peptide of any one of SEQ ID NOs:1-16; or (v) an E. canis bacterin, at least 1, 2, 3, 4, 5, 6, or all of TRP153, TRP36, TRP140, TRP28, TRP95, TRP19, TRP120 (e.g., TRP140, TRP36, and/or TRP19) and at least 1, 2, 3, 4, 5, or more peptides comprising or consisting of a peptide of any one of SEQ ID NOs:1-16; and a pharmaceutically acceptable excipient. Optionally, the immunogenic composition may comprise 1, 2, 3, all of Ank200, Ank153, OMP-1 and/or P30/28. In some embodiments, the immunogenic composition does not include TRP120. In some embodiments, the pharmaceutically acceptable excipient comprises or consists of an adjuvant. In some embodiments, the adjuvant comprises a triterpenoid saponin (e.g., Quil A), a sterol (e.g., cholesterol), and an immun