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US-12622957-B2 - Mycoplasma vaccine composition and methods

US12622957B2US 12622957 B2US12622957 B2US 12622957B2US-12622957-B2

Abstract

Described are vaccine compositions, methods of manufacture thereof, and methods of treating or preventing certain bacterial infections in humans and other mammals. For example, described are compositions comprising bacterial cell extracts that have undergone pretreatment such that lipid moieties have been cleaved from bacterial lipoproteins, thereby forming a vaccine composition that can stimulate a desired mammalian immune response while avoiding unwanted negative effects.

Inventors

  • Steven M. Szczepanek
  • STEVEN J. GEARY
  • EDAN R. TULMAN

Assignees

  • UNIVERSITY OF CONNECTICUT

Dates

Publication Date
20260512
Application Date
20201203

Claims (12)

  1. 1 . A vaccine composition comprising a de-lipidated or non-lipidated mollicute bacteria material, wherein the de-lipidated or non-lipidated bacteria material includes at least one of: a reduced amount of lipid moieties bound to membrane-associated lipoproteins relative to wildtype or untreated mollicute bacteria material; a reduced amount of membrane-associated lipoproteins relative to wildtype or untreated mollicute bacteria material; or a combination thereof, wherein the mollicute bacteria material is derived from any bacteria of the genus Mycoplasma or the genus Ureaplasma.
  2. 2 . The vaccine composition of claim 1 , wherein the de-lipidated or non-lipidated bacteria material is derived from at least one of wildtype or synthetic strains of Mycoplasma pneumoniae, Mycoplasma genitalium, Ureaplasma urealyticum, Mycoplasma hominis Mycoplasma gallisepticum, Mycoplasma pulmonis , or any combination thereof.
  3. 3 . The vaccine composition of claim 1 , wherein the mollicute bacteria material is at least one of a non-ionic detergent-soluble whole-cell extract fraction or derived from any bacteria of the genus Mycoplasma.
  4. 4 . The vaccine composition of claim 1 , wherein the mollicute bacteria material is derived from bacteria of the species Mycoplasma pneumoniae.
  5. 5 . The vaccine composition of claim 1 , wherein the mollicute bacteria material is selected from at least one of: live whole-cell bacteria, inactivated whole-cell bacteria, whole-cell extract, lysate, detergent-soluble whole-cell extract fraction, water-soluble whole-cell extract fraction, detergent-insoluble whole-cell extract fraction, and any combination thereof.
  6. 6 . The vaccine composition of claim 1 , wherein at least one of: the amount of membrane-associated lipoproteins is reduced at least about 50 percent relative to wildtype; the lipid moieties bound to membrane-associated lipoproteins are reduced at least about 50 percent relative to wildtype; or a combination thereof.
  7. 7 . The vaccine composition of claim 1 , wherein at least one of: the amount of membrane-associated lipoproteins is reduced at least about 70 percent relative to wildtype; the lipid moieties bound to membrane-associated lipoproteins are reduced at least about 70 percent relative to wildtype; or a combination thereof.
  8. 8 . The vaccine composition of claim 1 , wherein at least one of: the amount of membrane-associated lipoproteins is reduced at least about 85 percent relative to wildtype; lipid moieties bound to membrane-associated lipoproteins are reduced at least about 85 percent relative to wildtype; or a combination thereof.
  9. 9 . The vaccine composition of claim 1 , having at least one of an undetectable amount of lipid moieties bound to membrane-associated lipoproteins; an undetectable amount of membrane-associated lipoproteins; or a combination thereof.
  10. 10 . The vaccine composition of claim 1 , further comprising an adjuvant.
  11. 11 . The vaccine composition of claim 10 , wherein the adjuvant is monophosphoryl lipid A (MPLA).
  12. 12 . The vaccine composition of claim 1 , wherein: the vaccine composition further comprises at least one of a solvent, a buffer, a stabilizer, a carrier, a preservative, or a combination thereof; the vaccine composition is loaded into a hypodermic syringe, intravenous drip, nasal syringe, pipette, eye dropper, inhaler, atomizer, or dermal patch; or a combination thereof.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS The present application is a National Stage Entry of PCT/US2020/062994, filed 3 Dec. 2020, published as WO 2021/113433 A1, which claims the benefit of and priority to U.S. Provisional Patent Application Ser. No. 62/943,052 filed: 3 Dec. 2019 and titled: Mycoplasma Vaccine Composition and Methods, each of which is incorporated herein by reference in its entirety. BACKGROUND 1. Field of the Discovery Described are vaccine compositions, methods of manufacture thereof, and methods of treating or preventing certain bacterial infections in humans and other mammals. 2. Background Information Respiratory tract infections (RTIs) are the leading infectious-disease cause of death among children and the elderly, and fifth-leading cause of death overall, in the world today. (Niederman M, Ann. Intern. Med. 2009; 151(7):ITC4-1). The mollicute pathogen Mycoplasma pneumoniae is a major cause of dangerous RTIs, including pneumonia, and is responsible for over two million infections and 100,000 hospitalizations in the United States every year. (Waites, K. B., Xiao, L., Liu, Y., Balish, M. F., & Atkinson, T. P. (2017). Clinical Microbiology Revs., 30(3), 747-809). Additionally, mortality rates from M. pneumoniae pneumonia are very high, especially among children and elderly persons. (Bajantri B, Toolsie O, Venkatram S, Diaz-Fuentes G. J. Clin. Med. Res. 2018; 10(12):891-97). M. pneumoniae is highly transmissible through airborne fluid droplets from sneezing, coughing, or speaking, leading to rapidly spreading local epidemics in close-community environments such as schools, households, assisted living facilities, barracks, and dormitories. Besides infecting a large number of individuals, M. pneumoniae infection is very difficult to treat. Mollicute bacteria such as M. pneumoniae lack a peptidoglycan cell wall, a common drug target for antibiotic treatment using β-lactam antibiotics. Extant strains of M. pneumoniae are also beginning to exhibit resistance to macrolides and other treatment options. (Liu X, Jiang Y, Chen X, Li J, Shi D, Xin D. Biomed. Res. Int. 2014; 2014:320801). The high morbidity rate and numerous infection treatment hurdles suggest that a preventative M. pneumoniae vaccine would be very desirable. Unfortunately, previous attempts to create an M. pneumoniae vaccine failed because, for then-unknown reasons, experimental M. pneumoniae vaccines frequently exacerbated the disease among vaccinated individuals who later became infected. For example, in a 1967 clinical study a substantial percentage of volunteer patients who received an experimental vaccine suffered worse M. pneumoniae disease than patients who did not receive the vaccine. (Smith C B, Friedewald W T, Chanock R M. J. Am. Med. Ass'n, 199 (1967), 353-58). Recent studies have recapitulated this vaccine-enhanced disease (VED) phenomenon in mouse model. (Szczepanek S M et al., Infect Immun. 2012 March; 80(3):1007-14). These serious challenges highlight the grave importance of developing an efficacious, safe vaccine against mollicute bacteria such as M. pneumoniae. SUMMARY In certain aspects, the description provides a vaccine composition comprising de-lipidated bacteria material, e.g., bacteria, bacterial extract or bacterial lysate. In any of the aspects or embodiments described herein, the bacteria material may comprise live whole-cell bacteria, killed/inactivated whole-cell bacteria, whole-cell extract, fractions of whole-cell extract (e.g., aqueous fraction, nonaqueous fraction, insoluble fraction, etc.), components of fractionated whole-cell extract, admixtures from fractionated whole-cell extract, isolated bacterial proteins (such as, e.g., lipoproteins), fragments of bacterial proteins (such as, e.g., fragments of lipoproteins), lipid-associated membrane proteins (LAMPs), fragments of LAMPs, fractions having had LAMPs removed/extracted, and any combination thereof. In any of the described aspects or embodiments, the bacteria material may be completely de-lipidated or partially de-lipidated; completely non-lipidated or partially non-lipidated; and any combination thereof. In any of the described aspects or embodiments, the vaccine composition may further comprise one or more adjuvants. In any of the described aspects or embodiments, the adjuvant may comprise monophosphoryl lipid A (MPLA), aluminum derivatives (aluminum hydroxide, aluminum sulfate, aluminum phosphate, or potassium aluminum sulfate), oil-in-water emulsion composed of squalene (MF59), bacterial/viral Cystine phosphate Guanosine (CpG) derivatives (e.g. CpG 1018), Chilean soapbark tree extract (QS-21) or a combination thereof. Contemplated herein is the use of suitable adjuvants currently known or that become known. In any of the described aspects or embodiments, the bacteria material comprises material derived from a mollicute bacterium. In any of the described aspects or embodiments, the bacteria material comprises material derived from the genus M