Immunization with meningococcal class 1 outer membrane protein produced in Bacillus subtilis and reconstituted in the presence of Zwittergent or Triton X-100.
Vaccines against group B meningococcal infection tested in several field trials have all been extracts of the outer membrane of the bacteria. We have developed a single component vaccine based on the class 1 outer membrane protein P1 produced in a heterologous host Bacillus subtilis, and describe here its immunizing properties. The purified and denatured protein BacP1 was solubilized in SDS, followed by addition of an excess of a second detergent (Zwittergent 3-14 or Triton X-100). Immunization of mice showed that this process led to at least partial reconstitution of the native epitopes of the P1 protein. The immunogenicity of these BacP1 detergent preparations was further improved when administered together with adjuvants (aluminium hydroxide or monophosphoryl lipid A); high titers of antibodies were thus obtained with vaccine doses as low as 2 micrograms of protein. The antibodies elicited were essentially of IgG and reactive with protective epitopes present on the surface of meningococci. The bactericidal activity of the sera showed a good correlation to antibodies of the IgG1 and IgG2 isotypes, concomitantly increased in most sera.
Idänpään-Heikkilä
I
I
Department of Bacterial Vaccine Research and Molecular Bacteriology, National Public Health Institute, Helsinki, Finland.
Wahlström
E
E
Muttilainen
S
S
Nurminen
M
M
Käyhty
H
H
Sarvas
M
M
Mäkelä
P H
PH
D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D001412:Bacillus subtilis / Q000235:genetics* / Q000378:metabolism; D001425:Bacterial Outer Membrane Proteins / Q000096:biosynthesis* / Q000276:immunology*; D001428:Bacterial Vaccines / Q000276:immunology; D003902:Detergents / Q000737:chemistry*; D005822:Genetic Vectors; D051379:Mice; D009345:Neisseria meningitidis / Q000276:immunology*; D017830:Octoxynol / Q000737:chemistry*; D000644:Quaternary Ammonium Compounds / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology*
D000907:Antibodies, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D003902:Detergents; D000644:Quaternary Ammonium Compounds; D014614:Vaccines, Synthetic; C034730:zwittergent 3-12; D017830:Octoxynol