A vaccine comprising synthetically linked domains of choline binding protein A (CbpA) from Streptococcus pneumonia, and a new type of pneumococcus vaccine component in which a T-cell epitope (e.g. Pneulmolysin toxoid) is fused to immunogenic fragments of choline binding protein A (CbpA). This new fused vaccine component provides an easier, less costly and more efficient way to elicit an immune response to both the T-cell epitope and CbpA as compared to a mixture of separate antigens. The CbpA fragment used preferably comprises synthetically linked domains of CbpA. The CbpA peptide-pneumolysoid fusion construct is a viable broadly protective pneumococcal vaccine that potentially adds protection against other meningeal pathogens; and may be useful for treating or preventing infections such as sepsis, meningitis, and pneumonia. Also, SJ-13-0032, “YLN for Cardiac Indication,” involves using these vaccine components to avoid adverse cardiac events caused by pneumonia infections (This is co-owned with Univ. of Texas Health Science Center.) These cardiac events are common and deadly and can create what is often referred to as a "ticking time bomb" scenario.
Synthetic vaccine, Immunogenic Fusion Protein, choline binding protein, CbpA, Streptococcus pneumonia, pneumococcal infections, sepsis, meningitis, pneumonia, cardiac, YLN
Granted Patents or Published Applications
CbpA fragment (SJ-05-0036) issued May 13, 2014 as U.S. Patent No. 8,722,055; additional U.S. Appln. pending. CbpA peptide-pneumolysoid fusion construct (SJ-10-0028) pending in the U.S. and published as U.S. Pub. No. 2014/0023674.
Related Scientific References
Reyes LF, Restrepo MI, Hinojosa CA, Soni NJ, Anzueto A, Babu BL, Gonzalez-Juarbe N, Rodriguez AH, Jimenez A, Chalmers JD, Aliberti S, Sibila O, Winter VT, Coalson JJ, Giavedoni LD, Dela Cruz CS, Waterer GW, Witzenrath M, Suttorp N, Dube PH, Orihuela CJ. Severe Pneumococcal Pneumonia Causes Acute Cardiac Toxicity and Subsequent Cardiac Remodeling. Am J Respir Crit Care Med. 2017 Jun 14. doi: 10.1164/rccm.201701-0104OC. [Epub ahead of print] PubMed PMID: 28614669.
Gilley RP, González-Juarbe N, Shenoy AT, Reyes LF, Dube PH, Restrepo MI, Orihuela CJ. Infiltrated Macrophages Die of Pneumolysin-Mediated Necroptosis following Pneumococcal Myocardial Invasion. Infect Immun. 2016 Apr 22;84(5):1457-69. doi: 10.1128/IAI.00007-16. Print 2016 May. PubMed PMID: 26930705; PubMed Central PMCID: PMC4862731.
Brown AO, Mann B, Gao G, Hankins JS, Humann J, Giardina J, Faverio P, Restrepo MI, Halade GV, Mortensen EM, Lindsey ML, Hanes M, Happel KI, Nelson S, Bagby GJ, Lorent JA, Cardinal P, Granados R, Esteban A, LeSaux CJ, Tuomanen EI, Orihuela CJ. Streptococcus pneumoniae translocates into the myocardium and forms unique microlesions that disrupt cardiac function. PLoS Pathog. 2014 Sep 18;10(9):e1004383. doi: 10.1371/journal.ppat.1004383. eCollection 2014 Sep. PubMed PMID: 25232870; PubMed Central PMCID: PMC4169480.
Chen A, Mann B, Gao G, Heath R, King J, Maissoneuve J, Alderson M, Tate A, Hollingshead SK, Tweten RK, Briles DE, Tuomanen EI, Paton JC. 2015. Multivalent pneumococcal protein vaccines comprising pneumolysoid with epitopes/fragments of CbpA and/or PspA elicit strong and broad protection. Clin Vaccine Immunol 22:1079 –1089. doi:10.1128/CVI.00293-15.
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