RESUMO
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.
Assuntos
Formação de Anticorpos/efeitos dos fármacos , Antígenos/farmacologia , Proteínas da Membrana Bacteriana Externa , Proteínas de Transporte , Proteínas de Protozoários , Vacinas Sintéticas/farmacologia , Acetilmuramil-Alanil-Isoglutamina/análogos & derivados , Acetilmuramil-Alanil-Isoglutamina/farmacologia , Anticorpos/análise , Anticorpos Antibacterianos/análise , Anticorpos Antivirais/análise , Antígenos de Bactérias/imunologia , Antígenos de Protozoários/imunologia , Antígenos de Superfície/imunologia , Proteínas de Bactérias/imunologia , Cromatografia Líquida de Alta Pressão , Feminino , Adjuvante de Freund/farmacologia , Antígenos de Superfície da Hepatite B/imunologia , Plasmodium/imunologia , Streptococcus pyogenes/imunologia , Vacinas Sintéticas/imunologia , Vacinas Sintéticas/isolamento & purificaçãoRESUMO
The influence of the presence of a terminal COOH or CONH2 on the antigenic characters of synthetic immunogenic peptides has been studied on a streptococcal synthetic vaccine model. The obtained results show that when a peptide amide is used, the antibodies raised specifically against the amide group recognize neither free COOH nor the parent protein. The carboxamide group is thus unsuitable as was postulated for raising antibodies which recognize the peptide bond.
Assuntos
Amidas/imunologia , Antígenos de Bactérias/imunologia , Dióxido de Carbono/imunologia , Fragmentos de Peptídeos/imunologia , Streptococcus pyogenes/imunologia , Animais , Anticorpos Antibacterianos/biossíntese , Ligação Competitiva , Epitopos/análise , Feminino , Camundongos , Camundongos Endogâmicos BALB CRESUMO
Adjuvant-active murabutide (N-acetylmuramyl-L-alanyl-D-glutamine-alpha-n-butyl ester), devoid of the side effects of muramyl dipeptide (N-acetylmuramyl-L-alanyl-D-isoglutamine), was administered in saline with natural and synthetic hepatitis B surface antigens (HBsAgs). This derivative enhanced the antibody responses against natural HBsAg. The persistence of high antibody titers was the same in the murabutide-treated group as in the alum-treated group. A synergistic enhancement of the antibody was obtained when both adjuvants were administered together. Cell-mediated immunity to HBsAg, tested by the proliferative response of lymph node cells to the antigen, was also shown to be induced in mice treated with alum-associated murabutide. When administered with natural HBsAg, murabutide produced titers of total antibodies as high as did alum but lower titers of specific immunoglobulin E. High levels of antipeptide antibodies were obtained when a synthetic fragment [HBsAg(99-121)] conjugated to a toxoid carrier was administered with murabutide in saline.
