Measuring antigen-specific bactericidal responses to a multicomponent vaccine against serogroup B meningococcus

Giuliani, Marzia M.; Biolchi, Alessia; Serruto, Davide; Ferlicca, Francesca; Vienken, Kay; Oster, Philipp; Rappuoli, Rino; Pizza, Mariagrazia; Donnelly, John

doi:10.1016/j.vaccine.2010.05.014

Cited by 83 publications

(85 citation statements)

References 34 publications

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“…We anticipated that NHba (36)(37)(38), which was abundantly expressed by the isolates from both outbreaks, would elicit serum bactericidal antibodies (5). However, the isolates from both outbreaks were resistant to the bactericidal activity of mouse antiNHba antiserum.…”

Section: Discussionmentioning

confidence: 99%

Susceptibility of Meningococcal Strains Responsible for Two Serogroup B Outbreaks on U.S. University Campuses to Serum Bactericidal Activity Elicited by the MenB-4C Vaccine

Rossi

Beernink

Giuntini

et al. 2015

Clin. Vaccine Immunol.

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M eningococcal serogroup B outbreaks involving a total of 14 cases occurred on two university campuses in the United States in 2013 and 2014 (1). The outbreak at university A, which is located in New Jersey, started in March 2013 with a total of 9 cases documented in the campus population or in close contacts of the students (2). The outbreak at university B, which is located in California, started in November 2013 with a cluster of four cases (1). These cases were later connected to a fifth case in a student enrolled at university B, which had occurred 7 months earlier. The strains from the two outbreaks were from different clonal complexes and therefore were not epidemiologically related.In response to these campus outbreaks, the U.S. Food and Drug Administration approved the immunization of the students with a serogroup B meningococcal vaccine (Bexsero; Novartis Vaccines and Diagnostics) (2), which at the time was licensed in Europe, Canada, and Australia. The vaccine contains four primary components, each capable of eliciting complement-mediated serum bactericidal activity (3, 4), and is referred to here as MenB-4C. The four antigens are factor H binding protein (FHbp), neisserial heparin binding antigen (NHba), neisserial adhesin A (NadA), and a porin protein (PorA) with variable region (VR) sequence type P1.7-2,4 contained in outer membrane vesicles (OMV) (3, 4). Since most of the anti-PorA bactericidal activity is directed to VR2, a match between the vaccine PorA and strain PorA is usually described as sharing the P1.4 VR2 antigen (5).The purpose of the present study was to investigate the expression of MenB-4C vaccine antigens in representative isolates from each of the outbreaks and the susceptibility of the isolates to serum bactericidal activity induced by MenB-4C vaccination. We also assessed the contribution of anti-FHbp antibodies in eliciting serum bactericidal activity. MATERIALS AND METHODSMeningococcal outbreak strains. We received 15 case isolates from the Meningitis Laboratory, Meningitis and Vaccine Preventable Diseases Branch, Centers for Disease Control and Prevention (CDC), Atlanta, GA. Of these, 10 isolates were from the university A outbreak, and 5 were from the university B outbreak. The CDC provided data on the date of isolation, source (blood or cerebrospinal fluid [CSF] sample), multilocus sequence type (MLST), PorB amino acid sequence type, and amino acid sequence variants of the FHbp, NadA, NHba, and PorA vaccine antigens. The isolates from university A were from sequence type 409 (ST-409), which is uncommon in the United States but part of the more common ST-41/44 clonal complex. The isolates from university B were all from ST-32, which is a common ST/clonal complex among invasive serogroup B case isolates from the west coast of the United States (6).Control strains. The strains used as controls are summarized in Table 1 and were previously described. Neisseria meningitidis strain NZ98/254 is a relatively low expresser of FHbp identification (ID) 14 (subfamily B) (7) and was use...

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Section: Discussionmentioning

confidence: 99%

Susceptibility of Meningococcal Strains Responsible for Two Serogroup B Outbreaks on U.S. University Campuses to Serum Bactericidal Activity Elicited by the MenB-4C Vaccine

Rossi

Beernink

Giuntini

et al. 2015

Clin. Vaccine Immunol.

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“…A competitive inhibition SBA assay was performed as previously described (37). Briefly, rPorA P1.7-2,4 or P1.7,16 was added to a final concentration of 500 g/ml to the decomplemented pooled serum of mice.…”

Section: Methodsmentioning

confidence: 99%

Neisseria meningitidis Native Outer Membrane Vesicles Containing Different Lipopolysaccharide Glycoforms as Adjuvants for Meningococcal and Nonmeningococcal Antigens

Nagaputra

Rollier

Sadarangani

et al. 2013

Clin. Vaccine Immunol.

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“…NHBA is presented in 4CMenB as a fusion protein with the protein GNA1030 (the function of which has not been determined) (13,14). The potential to elicit relatively broad cross-protective responses has been demonstrated for NHBA (16), which, unlike fHbp, does not fall into discrete immunologically distinct groups. The NadA component belongs to variant group 3 (of five) and may provide protection against subvariants of variant groups 1, 2, and 3 (17)(18)(19).…”

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confidence: 99%

Genetic Distribution of Noncapsular Meningococcal Group B Vaccine Antigens in Neisseria lactamica

Lucidarme

Gilchrist

Newbold

et al. 2013

Clin Vaccine Immunol

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bThe poor immunogenicity of the meningococcal serogroup B (MenB) capsule has led to the development of vaccines targeting subcapsular antigens, in particular the immunodominant and diverse outer membrane porin, PorA. These vaccines are largely strain specific; however, they offer limited protection against the diverse MenB-associated diseases observed in many industrialized nations. To broaden the scope of its protection, the multicomponent vaccine (4CMenB) incorporates a PorA-containing outer membrane vesicle (OMV) alongside relatively conserved recombinant protein components, including factor H-binding protein (fHbp), Neisseria adhesin A (NadA), and neisserial heparin-binding antigen (NHBA). The expression of PorA is unique to meningococci (Neisseria meningitidis); however, many subcapsular antigens are shared with nonpathogenic members of the genus Neisseria that also inhabit the nasopharynx. These organisms may elicit cross-protective immunity against meningococci and/or occupy a niche that might otherwise accommodate pathogens. The potential for 4CMenB responses to impact such species (and vice versa) was investigated by determining the genetic distribution of the primary 4CMenB antigens among diverse members of the common childhood commensal, Neisseria lactamica. All the isolates possessed nhba but were devoid of fhbp and nadA. The nhba alleles were mainly distinct from but closely related to those observed among a representative panel of invasive MenB isolates from the same broad geographic region. We made similar findings for the immunogenic typing antigen, FetA, which constitutes a major part of the 4CMenB OMV. Thus, 4CMenB vaccine responses may impact or be impacted by nasopharyngeal carriage of commensal neisseriae. This highlights an area for further research and surveillance should the vaccine be routinely implemented.

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Measuring antigen-specific bactericidal responses to a multicomponent vaccine against serogroup B meningococcus

Cited by 83 publications

References 34 publications

Susceptibility of Meningococcal Strains Responsible for Two Serogroup B Outbreaks on U.S. University Campuses to Serum Bactericidal Activity Elicited by the MenB-4C Vaccine

Susceptibility of Meningococcal Strains Responsible for Two Serogroup B Outbreaks on U.S. University Campuses to Serum Bactericidal Activity Elicited by the MenB-4C Vaccine

Neisseria meningitidis Native Outer Membrane Vesicles Containing Different Lipopolysaccharide Glycoforms as Adjuvants for Meningococcal and Nonmeningococcal Antigens

Genetic Distribution of Noncapsular Meningococcal Group B Vaccine Antigens in Neisseria lactamica

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