Vaccination against Neisseria meningitidis using three variants of the lipoprotein GNA1870.
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.
Masignani
Vega
V
IRIS, Chiron Srl, via Fiorentina 1, 53100 Siena, Italy.
Comanducci
Maurizio
M
Giuliani
Marzia Monica
MM
Bambini
Stefania
S
Adu-Bobie
Jeannette
J
Arico
Beatrice
B
Brunelli
Brunella
B
Pieri
Alessandro
A
Santini
Laura
L
Savino
Silvana
S
Serruto
Davide
D
Litt
David
D
Kroll
Simon
S
Welsch
Jo Anne
JA
Granoff
Dan M
DM
Rappuoli
Rino
R
Pizza
Mariagrazia
M
D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D000942:Antigens, Bacterial / Q000145:classification / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001483:Base Sequence; D005260:Female; D005798:Genes, Bacterial; D006801:Humans; D007223:Infant; D008074:Lipoproteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009345:Neisseria meningitidis / Q000276:immunology* / Q000378:metabolism; D010802:Phylogeny; D020033:Protein Isoforms / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016415:Sequence Alignment; D014611:Vaccination
D000942:Antigens, Bacterial; D008074:Lipoproteins; D020033:Protein Isoforms; D011994:Recombinant Proteins