Analysis of the genetic variability and immunological properties of the NlpB antigen, a novel protein identified in Neisseria meningitidis

Introduction Bacterial meningitis is still a pressing public health problem worldwide. Infections with Neisseria meningitidis, in particular, are a major contributor in the incidence of bacterial meningitis and septicemia, two devastating diseases that can claim the lives of children and young adults in a matter of hours. Both the developed and developing countries are equally affected by meningococcal infections, and examples of endemic or epidemic states can be found in both cases regardless of their geographical location [1]. Meningococcal disease, if left untreated, has a mortality rate of 60 to 80%. Although this figure can be reduced to 10% through the use of antibiotics, the antibiotic therapy does not eliminate or decrease the incidence of meningococcal colonization at the nasopharynx within the general population, while at the same time being expensive, and providing only shortterm benefits; additionally, meningococcal disease often leaves permanent sequelae among survivors. The use of immunoprophylactic treatment is generally regarded, therefore, as the only effective means for the successful control of this infection [1]. Most cases of meningococcal disease are caused by serogroups A, B or C meningococci. Although efficacious polysaccharide-based vaccines have been available for a long time against serogroups such as A, C, W135 and Y [2], the capsular polysaccharide from serogroup B is poorly immunogenic due to its structural similarity with polysialic acid polymers present on the surface of human embryonic nervous tissue [3], and serogroup B vaccine research has therefore focused instead on subcapsular antigens such as the outer membrane proteins (OMP). Several different OMPs have been evaluated as vaccine candidates, either as individual subunits or as components of outer membrane vesicle (OMV) preparations. Although some of these formulations have shown promising results, their protective spectrum has so far been restricted to a relatively small number of antigenically related strains, and in general they fail to provide cross-protection against representative collections of epidemiologically relevant heterologous meningococcal strains. The publication in the year 2000 of the genome sequence of a N. meningitidis serogroup B strain spurred a renewed interest in the search for new protein antigens that could induce protective immunity against this serogroup [4], using bioinformatic tools to process genomic and proteomic data. In this context, the present report summarizes the results obtained with these techniques at the Meningococcal Disease Department of the Center for Genetic Engineering and Biotechnology, which resulted in the identification of lipoprotein NlpB (annotated as NMB0928 in the genome sequence) as a component of the OMV from N. meningitidis, used as the active ingredient of the VA-MENGOC-BC vaccine. Additionally, this report presents our results in regard to obtaining and characterizing NlpB as a new vaccine candidate against meningococcal disease.