Antibody responses elicited by a polyvalent vaccine containing synthetic diphtheric, streptococcal and hepatitis peptides coupled to the same carrier

Chedid, L; Jolivet, Michel; Audibert, F.; Przewlocki, Grzegorz; Beachey, Edwin H.; Gras-Masse, Hélène; Tartar, André

doi:10.1016/0006-291x(83)91682-0

Cited by 17 publications

(9 citation statements)

References 11 publications

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“…Although previous studies (7)(8)(9)(10)(11)(12)(13) have shown the feasibility of using chemically synthesized copies of M protein peptides as immunogens, the protective immunity evoked by these peptides has been restricted to the single M serotypes from which they were copied. It is true that one may produce multivalent vaccines by conjugating more than one synthetic peptide to the same carrier (21) or by polymerizing them to each other (22), but these approaches raise the problems associated with possible immunosuppression induced by repeated injections of the same carrier, or the potential toxicity of the polymerizing agent. Moreover, the orientation of the protective epitopes is more difficult to predict in such polymers.…”

Section: Discussionmentioning

confidence: 99%

“…They are designated S-CB7(23-35)C and S-M5 (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20), respectively. In addition, two hybrid peptides, S-M5(1-20)-S-CB7(23-35)C and S-M5(1-20)-S-CB7 (19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34) were synthesized by the solid-phase method of Merrifield (18) as previously described (10). The synthetic peptides were purified by gel filtration on columns of Sephadex G50, and further purified as needed by reverse-phase HPLC on Ultrasphere ODS (Whatman Inc., Clifton, NJ) (10).…”

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confidence: 99%

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Opsonic antibodies evoked by hybrid peptide copies of types 5 and 24 streptococcal M proteins synthesized in tandem.

Beachey¹,

Gras-Masse²,

Tarter³

et al. 1986

The Journal of Experimental Medicine

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M proteins project as a-helical coiled-coil fibrils from the cell surface of Streptococcus pyogenes (1,2). These surface fibrils render the organisms resistant to ingestion and killing by blood phagocytes (3). The antiphagocytic effect is neutralized by type-specific antibodies directed against the M protein. In addition to the type-specific antibodies, certain M proteins evoke crossreactive immune responses against sarcolemmal membranes of cardiac tissue (4, 5) and muscle myosin (6). The latter findings have hampered efforts to develop M protein vaccines against rheumatogenic strains of S. pyogenes because of the fear that the vaccines may trigger rather than prevent acute rheumatic fever and rheumatic heart disease. In an attempt to avoid heart crossreactive epitopes, we prepared vaccines from native and chemically synthesized subpeptide fragments of M protein. We found that selected synthetic peptides copying known amino acid sequences of different M proteins evoked type-specific protective immunity against the related streptococci without stimulating heart crossreactive immune responses (7-13). In this paper, we report that hybrid peptides containing copies of selected regions of two different serotypes of M protein synthesized in tandem evoke protective but not heart crossreactive immune'responses against both serotypes of S. pyogenes. Our findings may have bearing not only on the development of safe, multivalent M protein vaccines to protect against the many M serotypes of streptococci giving rise to acute rheumatic fever and rheumatic heart disease, but also on the development of multivalent hybrid vaccines against a variety of other infectious agents. Materials and MethodsNatural and Synthetic Peptides of Streptococcal M Protein. Natural polypeptide fragments of M protein were isolated and purified from limited digests of types 5 and 24 M proteins

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Opsonic antibodies evoked by hybrid peptide copies of types 5 and 24 streptococcal M proteins synthesized in tandem.

Beachey¹,

Gras-Masse²,

Tarter³

et al. 1986

The Journal of Experimental Medicine

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“…In addition, attempts to separate heterologous protein contaminants from the type-specific determinants were disappointing. Except for one investigation (22), all vaccine development since the 1970s has been based on animal studies and on an analysis of the immune response to a variety of M-protein preparations with and without adjuvants (10,26,27,37,78,104,216) and in combination with other antigens (37). In 1979, Beachey et al (22) used pepsin-extracted M24 protein (the N-terminal half of the native M molecule) to immunize human volunteers.…”

Section: M-protein Vaccinesmentioning

confidence: 99%

Streptococcal M protein: molecular design and biological behavior.

Fischetti¹

1989

Clinical Microbiology Reviews

158

249

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“…The times of elution of poly-S-34 and poly-PK 26 were shorter and longer, respectively. The peak of the polyvalent vaccine was collected in five different fractions and studied for the antigenic composition by ELISA with antisera that were monovalent for each peptide (8). All five fractions were shown to contain the four antigens in approximately the same proportions.…”

Section: Resultsmentioning

confidence: 99%

“…We have demonstrated previously that peptides of different specificities conjugated to tetanus toxoid produced non-cross-reactive antibodies of each specificity when administered with Freund complete adjuvant (FCA) (8). Moreover, these antibodies were shown to be biologically active.…”

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confidence: 99%

Induction of biologically active antibodies by a polyvalent synthetic vaccine constructed without carrier

Jolivet¹,

Audibert²,

Gras-Masse³

et al. 1987

Infect Immun

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Four synthetic peptides that copy fragments of two bacterial antigens (Streptococcus pyogenes M protein and diphtheria toxin), one viral antigen (hepatitis B surface antigen), and one parasitic antigen (circumsporozoite protein of Plasmodium knowlesi) were covalently bound within the same construct. This totally synthetic polyvalent administered to mice with Freund complete adjuvant or in saline with murabutide (an adjuvant-active muramyl peptide) elicited high levels of antibodies which, in certain cases, were shown to be biologically active. The results indicated that these antibodies recognized specifically the four peptides. None of the epitopes were immunodominant. It was also demonstrated that the association of several peptides enhanced their respective immunogenicities as compared with those of their homopolymers. Finally, this study shows that a totally synthetic vaccine administered in saline with a synthetic adjuvant can be immunogenic in the absence of a protein carrier.

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Antibody responses elicited by a polyvalent vaccine containing synthetic diphtheric, streptococcal and hepatitis peptides coupled to the same carrier

Cited by 17 publications

References 11 publications

Opsonic antibodies evoked by hybrid peptide copies of types 5 and 24 streptococcal M proteins synthesized in tandem.

Opsonic antibodies evoked by hybrid peptide copies of types 5 and 24 streptococcal M proteins synthesized in tandem.

Streptococcal M protein: molecular design and biological behavior.

Induction of biologically active antibodies by a polyvalent synthetic vaccine constructed without carrier

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