Prevention of Meningococcal Serogroup B Infections in Children: A Protein‐Based Vaccine Induces Immunologic Memory

Kleijn, Ester D. de; Groot, Ronald de; Lafeber, Arianne B.; Labadie, Jerry; Limpt, Cees J. P. van; Visser, John; Berbers, Guy A. M.; Alphen, Loek van; Rümke, H. C.

doi:10.1086/320993

Cited by 26 publications

(19 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Available sera from three different clinical phase II trials in children were used. These trials have been described earlier and are summarized in Table 1 (3)(4)(5). Only the prevaccination serum samples and the samples drawn postbooster were used for analysis.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Cross-Reactivity of Antibodies against PorA after Vaccination with a Meningococcal B Outer Membrane Vesicle Vaccine

et al. 2003

View full text Add to dashboard Cite

The cross-reactivity of PorA-specific antibodies induced by a monovalent P1.7-2,4 (MonoMen) and/or a hexavalent (HexaMen) meningococcal B outer membrane vesicle vaccine (OMV) in toddlers and school children was studied by serum bactericidal assays (SBA). First, isogenic vaccine strains and PorA-identical patient isolates were compared as a target in SBA, to ensure that the vaccine strains are representative for patient isolates. Geometric mean titers (GMTs) in SBA against patient isolates with subtypes P1.5-2,10 and P1.5-1,2-2 after vaccination with HexaMen were generally lower than those against vaccine strains with the same subtype, although the percentage of vaccine responders (>4-fold increase in SBA after vaccination) was not affected. Using various P1.7-2,4 patient isolates, GMTs as well as the number of vaccine responders were higher than for the P1.7-2,4 vaccine strain, indicating that the use of the P1.7-2,4 vaccine strain may have underestimated the immunogenicity of this subtype in HexaMen. Secondly, the cross-reactivity of antibodies induced by MonoMen and HexaMen was studied using several patient isolates that differed from the vaccine subtypes by having minor antigenic variants of one variable region (VR), by having a completely different VR or by having a different combination of VRs. MonoMen induced P1.4-specific antibodies that were crossreactive with P1.4 variants P1.4-1 and P1.4-3. HexaMen induced a broader cross-reactive antibody response against various patient isolates with one VR identical to a vaccine subtype or a combination of VRs included in HexaMen. Cross-reactivity, measured by a fourfold increase in SBA after vaccination, against these strains ranged from 23 to 92% depending on the subtype of the tested strain and was directed against both VR1 and VR2. The extended cross-reactivity of vaccinee sera induced by HexaMen against antigenic variants has important favorable implications for meningococcal B OMV vaccine coverage.

show abstract

Section: Methodsmentioning

confidence: 99%

“…A second OMV vaccine was constructed expressing only the P1.7-2,4 subtype (MonoMen). This vaccine was highly immunogenic in toddlers and induced a booster response in children previously vaccinated with HexaMen (4,5). The booster response was not only observed for the P1.7-2,4 subtype but to a lesser extent also for other subtypes included in HexaMen.…”

mentioning

confidence: 95%

Cross-Reactivity of Antibodies against PorA after Vaccination with a Meningococcal B Outer Membrane Vesicle Vaccine

et al. 2003

View full text Add to dashboard Cite

show abstract

“…One uses detergent-treated OMV vaccines prepared from mutant strains engineered to express more than one PorA (9). A second combines a detergent-treated OMV vaccine with three recombinant proteins containing five novel antigens that were identified as vaccine candidates by "reverse vaccinology" (14).…”

mentioning

confidence: 99%

Meningococcal Outer Membrane Vesicle Vaccines Derived from Mutant Strains Engineered To Express Factor H Binding Proteins from Antigenic Variant Groups 1 and 2

Koeberling

Giuntini

Seubert

et al. 2009

Clin Vaccine Immunol

View full text Add to dashboard Cite

Meningococcal outer membrane vesicle (OMV) vaccines, which are treated with detergents to decrease endotoxin activity, are safe and effective in humans. However, the vaccines elicit serum bactericidal antibody responses largely directed against PorA, which is antigenically variable. We previously prepared a native (non-detergent-treated) OMV vaccine from a mutant of group B strain H44/76 in which the lpxL1 gene was inactivated, which resulted in penta-acylated lipid A with attenuated endotoxin activity. To enhance protection, we overexpressed factor H binding protein (fHbp) from the antigenic variant 1 group. The vaccine elicited broad serum bactericidal antibody responses in mice against strains with fHbp variant 1 (ϳ70% of group B isolates) but not against strains with variant 2 or 3. In the present study, we constructed a mutant of group B strain NZ98/254 with attenuated endotoxin that expressed both endogenous variant 1 and heterologous fHbp variant 2. A mixture of the two native OMV vaccines from the H44/76 and NZ98/254 mutants stimulated proinflammatory cytokine responses by human peripheral blood mononuclear cells similar to those stimulated by control, detergent-treated OMV vaccines from the wild-type strains. In mice, the mixture of the two native OMV vaccines elicited broad serum bactericidal antibody responses against strains with heterologous PorA and fHbp in the variant 1, 2, or 3 group. By adsorption studies, the principal bactericidal antibody target was determined to be fHbp. Thus, native OMV vaccines from mutants expressing fHbp variants have the potential to be safe for humans and to confer broad protection against meningococcal disease from strains expressing fHbp from each of the antigenic variant groups.

show abstract

“…Moreover, immunization of volunteers with experimental vaccines based on outer-membrane vesicles demonstrated that bactericidal polyclonal antibodies are mainly directed against this protein, and the presence of these antibodies has been accepted as a marker for protection against infection caused by strains with the same serosubtype(s) as those of the vaccine strain (Rosenqvist et al, 1995;van der Voort et al, 1997;Longworth et al, 2002). During the past decade, single and multivalent vaccines composed of different PorA epitopes have been developed according to the most prevalent circulating serosubtypes in different geographical areas (Peeters et al, 1996;Cartwright et al, 1999;de Kleijn et al, 2000;Martin et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Antigenic and/or phase variation of PorA protein in non-subtypable Neisseria meningitidis strains isolated in Spain

Alcalá

Salcedo

Arreaza

et al. 2004

Journal of Medical Microbiology

View full text Add to dashboard Cite

Prevention of Meningococcal Serogroup B Infections in Children: A Protein‐Based Vaccine Induces Immunologic Memory

Cited by 26 publications

References 15 publications

Cross-Reactivity of Antibodies against PorA after Vaccination with a Meningococcal B Outer Membrane Vesicle Vaccine

Cross-Reactivity of Antibodies against PorA after Vaccination with a Meningococcal B Outer Membrane Vesicle Vaccine

Meningococcal Outer Membrane Vesicle Vaccines Derived from Mutant Strains Engineered To Express Factor H Binding Proteins from Antigenic Variant Groups 1 and 2

Antigenic and/or phase variation of PorA protein in non-subtypable Neisseria meningitidis strains isolated in Spain

Contact Info

Product

Resources

About