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Vaccination against Neisseria meningitidis using three variants of the lipoprotein GNA1870.
- Source :
-
The Journal of experimental medicine [J Exp Med] 2003 Mar 17; Vol. 197 (6), pp. 789-99. - Publication Year :
- 2003
-
Abstract
- Sepsis and meningitis caused by serogroup B meningococcus are devastating diseases of infants and young adults, which cannot yet be prevented by vaccination. By genome mining, we discovered GNA1870, a new surface-exposed lipoprotein of Neisseria meningitidis that induces high levels of bactericidal antibodies. The antigen is expressed by all strains of N. meningitidis tested. Sequencing of the gene in 71 strains representative of the genetic and geographic diversity of the N. meningitidis population, showed that the protein can be divided into three variants. Conservation within each variant ranges between 91.6 to 100%, while between the variants the conservation can be as low as 62.8%. The level of expression varies between strains, which can be classified as high, intermediate, and low expressors. Antibodies against a recombinant form of the protein elicit complement-mediated killing of the strains that carry the same variant and induce passive protection in the infant rat model. Bactericidal titers are highest against those strains expressing high yields of the protein; however, even the very low expressors are efficiently killed. The novel antigen is a top candidate for the development of a new vaccine against meningococcus.
- Subjects :
- Adult
Amino Acid Sequence
Animals
Antigens, Bacterial classification
Antigens, Bacterial genetics
Antigens, Bacterial metabolism
Base Sequence
Female
Genes, Bacterial
Humans
Infant
Lipoproteins genetics
Lipoproteins metabolism
Mice
Molecular Sequence Data
Neisseria meningitidis metabolism
Phylogeny
Protein Isoforms genetics
Protein Isoforms metabolism
Recombinant Proteins genetics
Recombinant Proteins immunology
Recombinant Proteins metabolism
Sequence Alignment
Antigens, Bacterial immunology
Lipoproteins immunology
Neisseria meningitidis immunology
Protein Isoforms immunology
Vaccination
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1007
- Volume :
- 197
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- The Journal of experimental medicine
- Publication Type :
- Academic Journal
- Accession number :
- 12642606
- Full Text :
- https://doi.org/10.1084/jem.20021911