Properties and clinical performance of vaccines containing outer membrane vesicles from Neisseria meningitidis

Holst, Johan; Martin, Diana; Arnold, Richard; Huergo, Concepción Campa; Oster, Philipp; O’Hallahan, Jane; Rosenqvist, Einar

doi:10.1016/j.vaccine.2009.04.071

Cited by 349 publications

(296 citation statements)

References 61 publications

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“…32 In the present study, reactions to MenABCWY formulations including OMV were more frequent relative to the other groups. Lowering the dosage of the OMV components from a full dose to a one-quarter dose resulted in only small differences in the proportions of subjects with reactions.…”

Section: Discussionmentioning

confidence: 39%

Immunogenicity and safety of investigational vaccine formulations against meningococcal serogroups A, B, C, W, and Y in healthy adolescents

Sáez-Llorens

Vaca²,

Abarca

et al. 2015

Human Vaccines & Immunotherapeutics

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This phase 2 study assessed the immunogenicity, safety, and reactogenicity of investigational formulations of meningococcal ABCWY vaccines, consisting of recombinant proteins (rMenB) and outer membrane vesicle (OMV) components of a licensed serogroup B vaccine, combined with components of a licensed quadrivalent meningococcal glycoconjugate vaccine (MenACWY-CRM). A total of 495 healthy adolescents were randomized to 6 groups to receive 2 doses (Months 0, 2) of one of 4 formulations of rMenB antigens, with or without OMV, combined with MenACWY-CRM, or 2 doses of rMenB alone or one dose of MenACWY-CRM then a placebo. Immunogenicity was assessed by serum bactericidal assay with human complement (hSBA) against serogroups ACWY and serogroup B test strains; solicited reactions and any adverse events (AEs) were assessed. Two MenABCWY vaccinations elicited robust ACWY immune responses, with higher seroresponse rates than one dose of MenACWY-CRM. Bactericidal antibody responses against the rMenB antigens and OMV components were highest in subjects who received 2 doses of OMV-containing MenABCWY formulations, with 68% of subjects achieving hSBA titers 5 against each of the serogroup B test strains. After the first dose, solicited local reaction rates were higher in the MenABCWY or rMenB groups than the MenACWY-CRM group, but similar across groups after the second dose, consisting mainly of transient injection site pain. Fever ( 38.0 C) was rare and there were no vaccine-related serious AEs. In conclusion, investigational MenABCWY formulations containing OMV components elicited highly immunogenic responses against meningococcal serogroups ACWY, as well as serogroup B test strains, with an acceptable safety profile. [NCT01210885]

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Section: Discussionmentioning

confidence: 39%

Immunogenicity and safety of investigational vaccine formulations against meningococcal serogroups A, B, C, W, and Y in healthy adolescents

Sáez-Llorens

Vaca²,

Abarca

et al. 2015

Human Vaccines & Immunotherapeutics

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“…Proper OMV cargo selection could be critical for pathogenesis, and therefore our results identify new opportunities for intervention against pathogenic bacteria. In addition, understanding how proteins are selectively packed into OMV may be useful to improve current OMVbased vaccines, which have already been used in humans in different parts of the world (49).…”

Section: Discussionmentioning

confidence: 99%

Selective Sorting of Cargo Proteins into Bacterial Membrane Vesicles

Haurat¹,

Aduse‐Opoku

Rangarajan

et al. 2011

Journal of Biological Chemistry

272

290

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In contrast to the well established multiple cellular roles of membrane vesicles in eukaryotic cell biology, outer membrane vesicles (OMV) produced via blebbing of prokaryotic membranes have frequently been regarded as cell debris or microscopy artifacts. Increasingly, however, bacterial membrane vesicles are thought to play a role in microbial virulence, although it remains to be determined whether OMV result from a directed process or from passive disintegration of the outer membrane. Here we establish that the human oral pathogen Porphyromonas gingivalis has a mechanism to selectively sort proteins into OMV, resulting in the preferential packaging of virulence factors into OMV and the exclusion of abundant outer membrane proteins from the protein cargo. Furthermore, we show a critical role for lipopolysaccharide in directing this sorting mechanism. The existence of a process to package specific virulence factors into OMV may significantly alter our current understanding of host-pathogen interactions.

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“…To control these outbreaks, vaccines based on the highly variable porin A protein were used, but Electronic supplementary material The online version of this article (doi:10.1208/s12248-016-9979-x) contains supplementary material, which is available to authorized users. these vaccines were not broadly effective against other invasive NmB strains (5,6).…”

Section: Introductionmentioning

confidence: 91%

The Dual Role of Lipids of the Lipoproteins in Trumenba, a Self-Adjuvanting Vaccine Against Meningococcal Meningitis B Disease

Luo

Friese

Runnels

et al. 2016

AAPS J

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ABSTRACT.Trumenba (bivalent rLP2086) is a vaccine licensed for the prevention of meningococcal meningitis disease caused by Neisseria meningitidis serogroup B (NmB) in individuals 10-25 years of age in the USA. The vaccine is composed of two factor H binding protein (fHbp) variants that were recombinantly expressed in Escherichia coli as native lipoproteins: rLP2086-A05 and rLP2086-B01. The vaccine was shown to induce potent bactericidal antibodies against a broad range of NmB isolates expressing fHbp that were different in sequence from the fHbp vaccine antigens. Here, we describe the characterization of the vaccine antigens including the elucidation of their structure which is characterized by two distinct motifs, the polypeptide domain and the N-terminal lipid moiety. In the vaccine formulation, the lipoproteins self-associate to form micelles driven by the hydrophobicity of the lipids and limited by the size of the folded polypeptides. The micelles help to increase the structural stability of the lipoproteins in the absence of bacterial cell walls. Analysis of the lipoproteins in Toll-like receptor (TLR) activation assays revealed their TLR2 agonist activity. This activity was lost with removal of the O-linked fatty acids, similar to removal of all lipids, demonstrating that this moiety plays an adjuvant role in immune activation. The thorough understanding of the structure and function of each moiety of the lipoproteins, as well as their relationship, lays the foundation for identifying critical parameters to guide vaccine development and manufacture.

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Properties and clinical performance of vaccines containing outer membrane vesicles from Neisseria meningitidis

Cited by 349 publications

References 61 publications

Immunogenicity and safety of investigational vaccine formulations against meningococcal serogroups A, B, C, W, and Y in healthy adolescents

Immunogenicity and safety of investigational vaccine formulations against meningococcal serogroups A, B, C, W, and Y in healthy adolescents

Selective Sorting of Cargo Proteins into Bacterial Membrane Vesicles

The Dual Role of Lipids of the Lipoproteins in Trumenba, a Self-Adjuvanting Vaccine Against Meningococcal Meningitis B Disease

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