Immunization of mice with Neisseria meningitidis serogroup B genomic expression libraries elicits functional antibodies and reduces the level of bacteremia in an infant rat infection model.
The feasibility of expression library immunization against the pathogenic bacterium Neisseria meningitidis was studied. A genomic library of N. meningitidis serogroup B strain CU385, containing 6000 individual clones, was constructed and divided into 10 sublibraries. Immunization of BALB/c mice with plasmid DNA from six sublibraries induced a humoral response, with recognition of several meningococcal proteins by Western blot. Three of these sublibraries elicited bactericidal antibodies against the homologous strain, and sera from mice immunized with one of these sublibraries reduced significantly the number of viable bacteria in blood of infant rats challenged with N. meningitidis. In addition, after DNA immunization, mice were boosted intraperitoneally with 5 x 10(2) colony forming units of strain CU385. Mice immunized with nine of the 10 libraries developed bactericidal antibodies 1 week after the boost and controls did not, demonstrating the priming capacity and specificity of our immunization strategy. Our study demonstrates, for the first time, that genomic immunization offers a novel approach for screening possible vaccine candidates against N. meningitidis.
Yero
C Daniel
CD
Division of Biotechnology, Department of Molecular Biology, Finlay Institute, Ave 27, La Lisa, Habana 11600, Cuba. dyero75@hotmail.com
Pajón
F Rolando
FR
Caballero
M Evelin
ME
Cobas
A Karem
AK
López
H Yamilé
HY
Fariñas
M Mildrey
MM
Gonzáles
B Sonia
BS
Acosta
D Armando
DA
D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis*; D016470:Bacteremia / Q000235:genetics / Q000276:immunology / Q000517:prevention & control*; D001428:Bacterial Vaccines / Q000276:immunology / Q000627:therapeutic use*; D001483:Base Sequence; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D015698:Genomic Library; D008297:Male; D008585:Meningitis, Meningococcal / Q000235:genetics / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D038541:Neisseria meningitidis, Serogroup B / Q000235:genetics* / Q000276:immunology*; D051381:Rats; D017208:Rats, Wistar; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*
D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D019444:Vaccines, DNA