Nonimmunodominant regions are effective as building blocks in a streptococcal fusion protein vaccine.
Identification of antigens that elicit protective immunity is essential for effective vaccine development. We investigated the related surface proteins of group B Streptococcus, Rib and alpha, as potential vaccine candidates. Paradoxically, nonimmunodominant regions proved to be of particular interest as vaccine components. Mouse antibodies elicited by Rib and alpha were directed almost exclusively against the C-terminal repeats and not against the N-terminal regions. However, a fusion protein derived from the nonimmunodominant N-terminal regions of Rib and alpha was much more immunogenic than one derived from the repeats and was immunogenic even without adjuvant. Moreover, antibodies to the N-terminal fusion protein protected against infection and inhibited bacterial invasion of epithelial cells. Similarly, the N-terminal region of Streptococcus pyogenes M22 protein, which is targeted by opsonic antibodies, is nonimmunodominant. These data indicate that nonimmunodominant regions of bacterial antigens could be valuable for vaccine development.
Stålhammar-Carlemalm
Margaretha
M
Department of Laboratory Medicine, Division of Medical Microbiology, Lund University, Sölvegatan 23, SE-22362 Lund, Sweden.
Waldemarsson
Johan
J
Johnsson
Eskil
E
Areschoug
Thomas
T
Lindahl
Gunnar
G
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood*; D000942:Antigens, Bacterial / Q000276:immunology*; D000954:Antigens, Surface / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology*; D004847:Epithelial Cells / Q000382:microbiology; D000939:Epitopes / Q000276:immunology; D016882:ISCOMs / Q000276:immunology*; D007114:Immunization; D008565:Membrane Proteins / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D013290:Streptococcal Infections / Q000097:blood* / Q000517:prevention & control*; D022541:Streptococcal Vaccines / Q000276:immunology*; D013292:Streptococcus agalactiae / Q000276:immunology*; D013297:Streptococcus pyogenes / Q000276:immunology
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D000954:Antigens, Surface; D001426:Bacterial Proteins; D000939:Epitopes; D016882:ISCOMs; D008565:Membrane Proteins; C081277:Rib protein, Streptococcus agalactiae; D022541:Streptococcal Vaccines; C077961:alpha C protein, group B streptococci