Marjatta Nurminen

The class 1 outer membrane protein of Neisseria meningitidis produced in Bacillus subtilis can give rise to protective immunity

The class 1 outer membrane protein of Neisseria meningitidis B:15:P1.7, 16 was expressed in Bacillus subtilis in high yield as intracellular aggregates. These were easy to isolate and the protein (called BacP1) could be solubilized under denaturing conditions. Sera of mice immunized with thus‐solubilized BacP1 contained high titres of antibodies that reacted with the class 1 protein of the meningococcal envelope in immunoblots but did not react with native meningococcal envelope in enzyme immunoassays (EIA) or with intact meningococci in bactericidal assays. However, when the BacP1 protein was complexed with heterologous (Salmonella) lipopolysaccharide, the ensuing sera reacted with meningococcal envelope preparations in both EIA and immunoblots, showed subtype‐specific bactericidal activity, and were protective in an infant rat meningitis model.

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.

Salmonella as an Invasive Enteric Pathogen

Salmonella can infect a surprisingly wide variety of hosts ranging from reptiles to birds to mammals. Yet the bacteria isolated are so close to each other in DNA sequence that they must be considered as one species. The species name is at this moment still uncertain, because of the earlier separation of its many serovars as species, and the familiarity of their names to both microbiologists and clinicians. A new name. Salmonella enterica, has therefore been proposed to cover the whole species, but this name has not (yet) been accepted.[1] The use of the serovar names as trivial names is a practical compromise, also adopted in this paper.