Functional and Specific Antibody Responses in Adult Volunteers in New Zealand Who Were Given One of Two Different Meningococcal Serogroup B Outer Membrane Vesicle Vaccines

Wedege, Elisabeth; Bolstad, Karin; Aase, Audun; Herstad, Tove Karin; McCallum, Lisa; Rosenqvist, Einar; Oster, Philipp; Martin, Diana

doi:10.1128/cvi.00039-07

Cited by 50 publications

(45 citation statements)

References 65 publications

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“…Significant relationships between IB scores and SBA were observed for LOS and the conserved proteins Omp85, RmpM, and NspA. Such covariations have been described previously in some studies (53,55), whereas other studies did not confirm that antibodies to RmpM and NspA could exert bactericidal activity (23,46).…”

Section: Discussionmentioning

confidence: 65%

Specificity of Subcapsular Antibody Responses in Ethiopian Patients following Disease Caused by Serogroup A Meningococci

Norheim

Aseffa

Yassin

et al. 2008

Clin Vaccine Immunol

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Dissecting the specificities of human antibody responses following disease caused by serogroup A meningococci may be important for the development of improved vaccines. We performed a study of Ethiopian patients during outbreaks in 2002 and 2003. Sera were obtained from 71 patients with meningitis caused by bacteria of sequence type 7, as confirmed by PCR or culture, and from 113 Ethiopian controls. Antibody specificities were analyzed by immunoblotting (IB) against outer membrane antigen extracts of a reference strain and of the patients' own isolates and by enzyme-linked immunosorbent assay for immunoglobulin G (IgG) levels against lipooligosaccharide (LOS) L11 and the proteins NadA and NspA. IB revealed that the main antigens targeted were the proteins PorA, PorB, RmpM, and Opa/OpcA, as well as LOS. MenA disease induced significant increases in IgG against LOS L11 and NadA. The IgG levels against LOS remained elevated following disease, whereas the IgG anti-NadA levels returned to acute-phase levels in the late convalescent phase. Among adults, the anti-LOS IgG levels were similar in acute-phase patient sera as in control sera, whereas anti-NadA IgG levels were significantly higher in acute-phase sera than in controls. The IgG antibody levels against LOS and NadA correlated moderately but significantly with serum bactericidal activity against MenA strains. Future studies on immune response during MenA disease should take into account the high levels of anti-MenA polysaccharide IgG commonly found in the population and seek to clarify the role of antibodies against subcapsular antigens in protection against MenA disease.

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Section: Discussionmentioning

confidence: 65%

Specificity of Subcapsular Antibody Responses in Ethiopian Patients following Disease Caused by Serogroup A Meningococci

Norheim

Aseffa

Yassin

et al. 2008

Clin Vaccine Immunol

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“…As with nhba, however, the FetA VR repertoires of the two species appear to be mainly nonoverlapping. In addition, none of the isolates were found to possess the vaccine variant F1-5 (48), while a previous study of functional and specific antibody responses to the PorA P1.4 OMV failed to correlate elicited FetA IgG levels with serum bactericidal antibody (SBA) activity against the homologous vaccine strain (49). Therefore, immune responses to any meningococcal FetA component, against which immunogenicity tends to be variant specific (36), are unlikely to influence N. lactamica carriage and vice versa.…”

Section: Discussionmentioning

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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“…We tested the ability of human fH to regulate rat C3 deposition on two group B N. meningitidis strains, H44/76 and NZ98/254 (25,28,31,32,41,47) and to regulate rabbit C3 deposition on group A strain A2594, group B strain H44/76, and group C strain 4243. Strain H44/76 also was used to investigate the survival of organisms in the bloodstreams of infant rats upon administration of human fH.…”

Section: Methodsmentioning

confidence: 99%

Binding of Complement Factor H (fH) to Neisseria meningitidis Is Specific for Human fH and Inhibits Complement Activation by Rat and Rabbit Sera

Granoff¹,

Welsch²,

2009

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Complement factor H (fH), a molecule that downregulates complement activation, binds to Neisseria meningitidis and increases resistance to serum bactericidal activity. We investigated the species specificity of fH binding and the effect of human fH on downregulating rat (relevant for animal models) and rabbit (relevant for vaccine evaluation) complement activation. Binding to N. meningitidis was specific for human fH (low for chimpanzee fH and not detected with fH from lower primates). The addition of human fH decreased rat and rabbit C3 deposition on the bacterial surface and decreased group C bactericidal titers measured with rabbit complement 10-to 60-fold in heat-inactivated sera from human vaccinees. Administration of human fH to infant rats challenged with group B strain H44/76 resulted in an fH dose-dependent increase in CFU/ml of bacteria in blood 8 h later (P < 0.02). At the highest fH dose, 50 g/rat, the geometric mean number of CFU per ml was higher than that in control animals (1,050 versus 43 [P < 0.005]). The data underscore the importance of binding of human fH for survival of N. meningitidis in vitro and in vivo. The species specificity of binding of human fH adds another mechanism toward our understanding of why N. meningitidis is strictly a human pathogen.

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Functional and Specific Antibody Responses in Adult Volunteers in New Zealand Who Were Given One of Two Different Meningococcal Serogroup B Outer Membrane Vesicle Vaccines

Cited by 50 publications

References 65 publications

Specificity of Subcapsular Antibody Responses in Ethiopian Patients following Disease Caused by Serogroup A Meningococci

Specificity of Subcapsular Antibody Responses in Ethiopian Patients following Disease Caused by Serogroup A Meningococci

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

Binding of Complement Factor H (fH) to Neisseria meningitidis Is Specific for Human fH and Inhibits Complement Activation by Rat and Rabbit Sera

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