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Glutamyl trna synthetase (GTS) fragments

A technology of glutamyl and synthetase, applied in the directions of DNA/RNA fragments, recombinant DNA technology, enzymes, etc., can solve the problem of not providing operation examples, etc., and achieve the effect of high sequence identity

Inactive Publication Date: 2011-11-09
PROTEA VACCINE TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The use of a subgroup of 432 of these protein sequences as immunization antigens has also been proposed, but no working examples of using proteins as antigens to produce vaccines have been provided

Method used

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  • Glutamyl trna synthetase (GTS) fragments
  • Glutamyl trna synthetase (GTS) fragments
  • Glutamyl trna synthetase (GTS) fragments

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0133] Embodiment 1.GtS fragment

[0134] The amino acid sequence of Streptococcus pneumoniae GtS from serotype 4TIGR4 strain (Accession No. NP_346492) is represented by SEQ ID NO: 1:

[0135] 1MSKDIRVRYA PSPTGLLHIG NARTALFNYL YARHHGGTFL IRIEDTDRKR HVEDGERSQL

[0136] 61ENLRWLGMDW DESPESHENY RQSERLDLYQ KYIDQLLAEG KAYKSYVTEE ELAAERERQE

[0137] 121 VAGETPRYIN EYLGMSEEEK AAYIAEREAA GIIPTVRLAV NESGIYKWHD MVKGDIEFEG

[0138] 181GNIGGDWVIQ KKDGYPTYNF AVVIDDHDMQ ISHVIRGDDH IANTPKQLMV YEALGWEAPE

[0139] 241 FGHMTLIINS ETGKKLSKRD TNTLQFIEDY RKKGYLPEAV FNFALLGWN PGGEDEIFSR

[0140] 301EEFIKLFDEN RLSKSPAAFD QKKLDWMSND YIKNADLETI FEMAKPFLEE AGRLTDKAEK

[0141] 361 LVELYKPQMK SVDEIIPLTD LFFSDFPELT EAEREVMTGE TVPTVLEAFK AKLEAMTDDE

[0142] 421 FVTENIFPQI KAVQKETGIK GKNLFMPIRI AVSGEMHGPE LPDTIFLLGR EKSIQHIENM

[0143] 481LKEISK

[0144] A fragment of the above protein lacking the N-terminal amino acid 1-332 amino acids was generated. This fragment, called GtS(333-486), comprises 15...

Embodiment 2

[0162] Example 2. Homology to humans

[0163] The homology test comparing the amino acid sequence of the GtS (333-486) ​​fragment of SEQ ID NO: 3 with the human genome sequence was performed using http: / / blast.ncbi.nlm.nih.gov / Blast.cgi.

[0164] The highest homology was found between the S. pneumoniae GtS fragment and the human protein glutamyl-tRNA synthetase 2 (Human GtS-2, Gene ID: 124454EARS2, SEQ ID NO: 12). The sequence identity between the complete S. pneumoniae GtS protein sequence (SEQ ID NO: 1 ) and the human GtS-2 protein (SEQ ID NO: 12) is 29%. The sequence identity between S. pneumoniae GtS fragment 333-486 and human complete GtS-2 (compare SEQ ID NO: 2 with SEQ ID NO: 12) is 7.66%, while GtS fragment 333-486 (SEQ ID NO: 2 ) with the corresponding amino acid residues of the human GtS-2 sequence (residues 361-521 of SEQ ID NO: 12) was 18%. The N-terminal fragment of S. pneumoniae GtS (residues 5-332 of SEQ ID NO: 1) shares 37% sequence identity with the correspo...

Embodiment 3

[0166] Example 3. Homology to different S. pneumoniae strains

[0167] The homology between the GtS (333-486) ​​fragment of SEQ ID NO: 3 and other S. pneumoniae strains was checked using the NCBI-Blast tool. As shown in Table 1, all S. pneumoniae strains examined had at least 98% identity to SEQ ID NO: 3 and 100% identity (in the relevant regions) to SEQ ID NO: 2.

[0168] Table 1.

[0169]

[0170]

[0171] The sequence mutations (up to two differences per two strains) found between the strains were: L / F 382, ​​G / D 400, K / E 421, I / V 466 and M / I 481 (according to SEQ ID NO: 1 number).

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Abstract

The present invention relates to polypeptide fragments, including variants and analogs, of Streptococcus pneumonia (S. pneumoniae) glutamyl tRNA synthetase (GtS) protein and to vaccines comprising such polypeptide fragments. In particular, the present invention relates to the use of such vaccines for eliciting protective immunity to S. pneumoniae.

Description

field of invention [0001] The present invention relates to the protein glutamyl tRNA synthetase (GtS) derived from the cell wall of Streptococcus pneumoniae (S. pneumoniae). In particular, the present invention relates to immunogenic fragments of GtS and their use as polypeptide-based vaccines to elicit protective immunity against S. pneumoniae. Background of the invention [0002] Streptococcus pneumoniae belongs to the commensal flora of the human respiratory tract but can also cause invasive infections such as meningitis and sepsis. Most children in the developing world become nasopharyngeal carriers of S. pneumoniae. Many develop pneumococcal disease, which can be an invasive infection (eg, bacteremia, sepsis, or meningitis), or a mucosal infection (eg, pneumonia and otitis media). Streptococcus pneumoniae is the leading cause of non-epidemic childhood meningitis in Africa and other parts of the developing world. Approximately 1 to 2 million children die each year fro...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12N9/00A61K39/09A61K38/53A61K38/16A61P31/04
CPCA61K38/00C12N9/93A61K39/092A61P31/04A61P37/00A61K39/09C07K14/315C12N15/11
Inventor 亚法·米兹拉西-内本兹霍尔迈克尔·塔尔罗恩·达冈
Owner PROTEA VACCINE TECH
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