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Synthetic peptide fragments of streptococcal M proteins
Abstract:
The surface M proteins of group A streptococci prevent phagocytosis by the non-immune host but antibodies subsequently developed against these M proteins opsonize the organism to allow phagocytosis and killing. In some cases, antibodies developed against M proteins are cross-reactive with host tissue and have been implicated in rheumatic fever. Peptide fragments of several serotypes, namely type 24, 5 and 6 M proteins were chemically synthesized and tested for their ability to induce protective and tissue cross-reactive antibodies in rabbits. Two synthetic 35 residue peptides of type 24 M protein, S-CB3 and S-CB7 had previously been shown to evoke high ELISA titers as well as opsonic antibody titers in each of three rabbits. Neither contained host tissue cross-reactive antibodies when examined with human heart tissue. Subpeptides of CB7 were synthesized to identify the smallest protective epitope. Three synthetic subpeptides (S-CB7-(13-35), - (18-35) and - (23-35) C were covalently linked to tetanus toxoid and evoked opsonic antibodies in rabbits and thus protective immunity with no tissue cross-reactive epitopes. Synthetic peptides of the NH2-terminal region of peptide M 5, which is known to contain cardiac tissue cross-reactive epitopes, were also tested. When covalently linked to tetanus toxoid, the synthetic peptide S-M 5 (1-20), but not S-M5 (20-40), evoked antibodies which were protective against type 5 streptococci; no heart cross-reactive antibodies were evoked even when large excesses of the synthetic peptides were injected.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Researchers developed synthetic peptides from M proteins of Group A Streptococcus to induce protective antibodies. These peptides offer immunity against infection without causing harmful cross-reactions with host tissues like the heart.
Area of Science:
- Immunology
- Microbiology
- Molecular Biology
Background:
- Group A Streptococcus (GAS) surface M proteins evade host immune responses.
- Antibodies against M proteins can provide protection but may cross-react with host tissues, potentially causing rheumatic fever.
- Identifying specific M protein epitopes is crucial for developing safe and effective vaccines.
Purpose of the Study:
- To synthesize and test peptide fragments of GAS M proteins for their ability to induce protective and non-tissue-cross-reactive antibodies.
- To identify the smallest protective epitope within M protein type 24.
- To investigate the immunogenicity and cross-reactivity of synthetic peptides from M protein type 5.
Main Methods:
- Chemical synthesis of M protein peptide fragments from serotypes 24, 5, and 6.
- Testing synthesized peptides in rabbits for antibody induction (ELISA, opsonic assays).
- Assessing antibody cross-reactivity with human heart tissue.
- Covalent linkage of peptides to tetanus toxoid to enhance immunogenicity.
Main Results:
- Synthetic peptides S-CB3 and S-CB7 from M protein type 24 induced high ELISA and opsonic antibody titers in rabbits without heart cross-reactivity.
- Subpeptides of S-CB7, when linked to tetanus toxoid, evoked protective immunity with no observed tissue cross-reactivity.
- A synthetic peptide from the NH2-terminal region of M protein type 5 (S-M5 (1-20)) induced protective antibodies against type 5 GAS without heart cross-reactivity.
Conclusions:
- Synthetic M protein peptides can elicit protective immunity against GAS.
- Specific peptide fragments can induce protective antibodies without causing autoimmune reactions targeting host tissues.
- This approach holds promise for developing safer vaccines against GAS infections.