Human immune response to immunization with a structurally defined polypeptide fragment of streptococcal M protein.
We tested the ability of pepsin-extracted, highly purified M protein to induce type-specific immunity in experimental animals and humans. M protein was prepared from limited peptic digests of whole group A type 24 streptococci and was purified to chemical homogeneity as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, quantitative amino acid analysis, and Edman degradation. For vaccination, the lyophilized M24 protein preparation (pep M24) was precipitated in aluminum hydroxide. When injected into laboratory animals, alum-precipitated pep M24 produced type-specific protective antibodies and was free of non-type-specific immunoreactivity. In man, skin tests with 1-microgram doses of pep M24 were negative in all 37 adults tested. 12 adult human volunteers received two-four subcutaneous injections of 100-200 micrograms of alum-precipitated pep M24 at intervals of at least 2 wk. The immune response to pep M24 was measured by a variety of assays designed to detect (a) type-specific humoral antibodies (opsonophagocytic, long chain, and mouse protection tests); (b) total humoral antibodies (complement fixation and enzyme-linked immunosorbent assay); (c) cellular immunity (skin tests); and (d) heart cross-reactive antibodies (immunofluorescence). Type-specific opsonic antibodies developed in 10 of the 12 vaccinees, and positive delayed-type skin tests developed in 11. Immune sera from two of the vaccinees were effective in mouse-protection tests against challenge with M24 but not M6 streptococci. None of the volunteers developed heart-reactive antibodies or antibodies to non-type-specific M protein antigens. Alum-precipitated pep M24 was well-tolerated in man, and no serious local or systemic reactions were observed. Thus, pep M24 induces type-specific, protective antibodies in doses that are well-tolerated in man.
D000328:Adult; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis*; D000942:Antigens, Bacterial / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology* / Q000302:isolation & purification; D001428:Bacterial Vaccines / Q000276:immunology*; D005260:Female; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology; D008297:Male; D051379:Mice; D009206:Myocardium / Q000276:immunology; D009895:Opsonin Proteins / Q000096:biosynthesis; D010455:Peptides / Q000276:immunology* / Q000302:isolation & purification; D011817:Rabbits; D012882:Skin Tests; D013290:Streptococcal Infections / Q000517:prevention & control; D013297:Streptococcus pyogenes / Q000032:analysis / Q000276:immunology*
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D009895:Opsonin Proteins; D010455:Peptides