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

Yero, Daniel; Pajón, F. Rolando; Caballero, M. Evelin; Cobas, A. Karem; Lopéz, Horacio; Fariñas, Mildrey; Gonzáles, B. Sonia; Acosta, Armando

doi:10.1016/j.vaccine.2004.07.032

Cited by 18 publications

(7 citation statements)

References 41 publications

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“…The ability of the sera from immunized mice to confer protection against N. meningitidis bacteraemia in infant rats was performed as previously described (Yero et al, 2005). In brief, 5-6-day-old infant rats (outbred Wistar; CENPALAB) were randomly distributed in groups of six animals per pool of sera.…”

Section: G Sardiñ As and Others 198mentioning

confidence: 99%

Neisseria meningitidis antigen NMB0088: sequence variability, protein topology and vaccine potential

Sardiñas

Yero

Climent

et al. 2009

Journal of Medical Microbiology

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The significance of Neisseria meningitidis serogroup B membrane proteins as vaccine candidates is continually growing. Here, we studied different aspects of antigen NMB0088, a protein that is abundant in outer-membrane vesicle preparations and is thought to be a surface protein. The gene encoding protein NMB0088 was sequenced in a panel of 34 different meningococcal strains with clinical and epidemiological relevance. After this analysis, four variants of NMB0088 were identified; the variability was confined to three specific segments, designated VR1, VR2 and VR3. Secondary structure predictions, refined with alignment analysis and homology modelling using FadL of Escherichia coli, revealed that almost all the variable regions were located in extracellular loop domains. In addition, the NMB0088 antigen was expressed in E. coli and a procedure for obtaining purified recombinant NMB0088 is described. The humoral immune response elicited in BALB/c mice was measured by ELISA and Western blotting, while the functional activity of these antibodies was determined in a serum bactericidal assay and an animal protection model. After immunization in mice, the recombinant protein was capable of inducing a protective response when it was administered inserted into liposomes. According to our results, the recombinant NMB0088 protein may represent a novel antigen for a vaccine against meningococcal disease. However, results from the variability study should be considered for designing a cross-protective formulation in future studies.

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Section: G Sardiñ As and Others 198mentioning

confidence: 99%

Neisseria meningitidis antigen NMB0088: sequence variability, protein topology and vaccine potential

Sardiñas

Yero

Climent

et al. 2009

Journal of Medical Microbiology

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“…We have previously obtained an expression library of Neisseria meningitidis serogroup B (MenB) constructed into a plasmid suitable for DNA vaccination (Yero et al , 2005). The total library was composed of c .…”

Section: Characterization Of the Antibody Response Elicited After Mementioning

confidence: 99%

“…6000 individual plasmids arrayed into 96‐well microtiter plates. Library fractionation and plasmid pool purification have also been described (Yero et al , 2005). In the present study, we performed a first immunization schedule with the MenB total library in order to evaluate the activation of lymphocytes after immunization.…”

Section: Characterization Of the Antibody Response Elicited After Mementioning

confidence: 99%

“…Both assays are considered laboratory correlates of protection to evaluate MenB vaccine candidates (Vermont & van den Dobbelsteen, 2002). The bactericidal assay was carried out as described by Frasch & Robbins (1978) and the infant rat protection experiments were performed as previously reported for strain CU385 (Yero et al , 2005). After the OMV boost, all the DNA‐primed mice developed bactericidal antibodies, and the titer was higher (more than a twofold dilution) in such groups primed with sublibraries L1–L9 compared with the group primed with the empty vector (Table 1).…”

Section: Characterization Of the Antibody Response Elicited After Mementioning

confidence: 99%

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A novel method to screen genomic libraries that combines genomic immunization with the prime-boost strategy

Yero

Pajón

Caballero

et al. 2007

FEMS Immunol Med Microbiol

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We employed a prime-boost regimen in combination with the expression library immunization protocol to improve the protective effectiveness of a genomic library used as immunogen. To demonstrate the feasibility of this novel strategy, we used as a prime a serogroup B Neisseria meningitidis random genomic library constructed in a eukaryotic expression vector. Mice immunized with different fractions of this library and boosted with a single dose of meningococcal outer membrane vesicles elicited higher bactericidal antibody titers compared with mice primed with the empty vector. After the boost, passive administration of sera from mice primed with two of these fractions significantly reduced the number of viable bacteria in the blood of infant rats challenged with live N. meningitidis. The method proposed could be applied to the identification of subimmunogenic antigens during vaccine candidate screening by employing expression library immunization.

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“…In other cases, no negative effects are seen (74); the difference will always be pathogen and model specific. Nonetheless, in an attempt to boost the immune responses generated by genomic libraries of ELI, a live attenuated strain of Neisseria meningitidis was inoculated after DNA immunization (95). In this experiment, 9 out of 10 sublibraries induced bactericidal activity against a challenge with Neisseria, reflecting the ability of DNA genomic libraries to prime the immune system.…”

Section: Main Approaches For Elimentioning

confidence: 99%

Expression Library Immunization: a Road Map for Discovery of Vaccines against Infectious Diseases

Talaat

Stemke-Hale

2005

Infect Immun

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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

Cited by 18 publications

References 41 publications

Neisseria meningitidis antigen NMB0088: sequence variability, protein topology and vaccine potential

Neisseria meningitidis antigen NMB0088: sequence variability, protein topology and vaccine potential

A novel method to screen genomic libraries that combines genomic immunization with the prime-boost strategy

Expression Library Immunization: a Road Map for Discovery of Vaccines against Infectious Diseases

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