1998 Fiscal Year Final Research Report Summary
Development of group A streptococcal vaccine using mucosal immune system.
| Project/Area Number |
08670900
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Kagoshima University |
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Principal Investigator |
YOSHINAGA Masao Faculty of Medicine, Kagoshima University, Associate Professor, 医学部, 助教授 (10145469)
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| Co-Investigator(Kenkyū-buntansha) |
NOMURA Yuichi University Hospital, Kagoshima University, Assistant Professor, 医学部・附属病院, 講師 (90237884)
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| Project Period (FY) |
1996 – 1998
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| Keywords | group A streptococci / M protein / peptide / vaccine / mucosal immunity / 鼻咽腔免疫 |
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| Research Abstract |
Recent studies by overlapping synthetic peptides have revealed that major epitopes for IgG antibodies existed in the sequences of the C region of the streptococcal M protein) and that some of them may be a combination of a single break (b-turn and b-sheet, called as the turn, hereafter) in conformation in each C repeal and an adjacent sequence (a-helix) before or after the turns. The sequence just after the turn shows the homology with mammalian myosin. Purpose of the present study is to clarify the role of the combination of the turn and the adjacent sequence to develop a streptococcal vaccine candidate that shows better immunogenicity, no cross-reactivity with myosin, and greater opsonophagocytic reactivity. Peptides were synthesized based on the M6 molecules The M6 M protein has 2 turns in the C region. Each peptide was made to have a combination of a turn and an adjacent sequence, before, after, or both of the turn, then 6 peptides were synthesized. Each peptide was administered to
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3 rabbits and the serum was purified to a peptide-specific antibody with affinity columns. The antibodies with the combination of the turn and the sequence after the turn showed the greatest immunogenicity, and the difference in one amino acid in the turn affected the immunogenicity of these peptides. On the other hand, the peptides with the sequence after the turn showed non-specific cross-reactivity with skeletal myosin, but not to cardiac myosin. The cross-reactivity was not due to the sequence homology between the C region and myosin. The peptides with a combination of the turn and the sequence before the turn did not induce any cross-reactivity with myosin. All anti peptide specific antibodies showed good opsonophagocytic activity when high antibody titers to the C region were obtained. These data suggest that the combination of the turn and the adjacent sequence before the turn will be a candidate of choice for a streptococcal vaccine, because we are concerned about the possibility of evoking non-specific cross-reactivity of anti C region antibody with myosin. Less
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