Immunologic Response of Man to Group B Meningococcal Polysaccharide Vaccines

Wyle, Frederic A.; Artenstein, Malcolm S.; Brandt, Brenda L.; Tramont, Edmund C.; Kasper, Dennis L.; Altieri, Patricia L.; Berman, Sanford; Lowenthal, Joseph P.

doi:10.1093/infdis/126.5.514

Cited by 421 publications

(189 citation statements)

References 14 publications

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“…Four of the serogroups (A, C, Y, W) can be controlled with capsular polysaccharidebased vaccines. A capsular polysaccharide-based vaccine approach was not feasible for protection against N. meningitidis serogroup B (NmB) (2) due to the low immunogenicity of the serogroup B capsular polysaccharide (3), which is similar to structures found on human neuronal cells (4). In regions where the A, C, Y, W vaccines are routinely used, endemic NmB disease is often the most common cause of meningococcal disease in infants, children, and young adults (1).…”

Section: Introductionmentioning

confidence: 99%

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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Section: Introductionmentioning

confidence: 99%

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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“…In the late 1960s and early 1970s, it was found that purified group-A and group-C meningococcal capsular polysaccharides could induce bactericidal antibodies when used for immunisation (Wyle et al, 1972). Protection against meningococcal diseases was thereafter proven in several field trials with these polysaccharide vaccines.…”

Section: Department Of Laboratory Medicine Ruchill Hospital Glasgowmentioning

confidence: 99%

“…(ii) A major problem in the development of vaccines against meningococcal diseases is the group-B capsular polysacc haride, a homopolymer of a(2+8)-sialic acid, that is poorly immunogenic (Wyle et al, 1972). The linear sugar epitopes of this polysaccharide do not seem to be immunogenic at all and the low-affinity antibodies, when induced, appear to be directed against conformational epitopes (Jennings et al, 1985).…”

Section: Department Of Laboratory Medicine Ruchill Hospital Glasgowmentioning

confidence: 99%

Meningococcal infection: --a review based upon papers presented at the 155th Meeting of the Pathological Society of Great Britain and Ireland at Southampton; 8 July, 1987

Bannister¹

1988

Journal of Medical Microbiology

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“…1 blue) (3). PSA is atypical because it induces a weak or null immune response when administered to adults (4). Some attribute this effect to the presence of similar carbohydrates in humans (5-7).…”

mentioning

confidence: 99%

Extracellular structure of polysialic acid explored by on cell solution NMR

Azurmendi

Vionnet

Wrightson

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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The capsular polysaccharide of the pathogens Neisseria meningitidis serogroup B and of Escherichia coli K1, ␣(2 3 8) polysialic acid (PSA), is unusual, because when injected into adult humans, it generates little or no antibody. In contrast, people infected with these pathogens generate specific serum antibodies. A structural study on cells is used to address this anomaly by characterizing antigen structures in vivo. We introduce on cell multidimensional solution NMR spectroscopy for direct observation of PSA on E. coli bacteria. Using 13 C, 15 N-labeled PSA, we applied a combination of heteronuclear NMR methods, such as heteronuclear single quantum coherence, HNCA, and HNCO, in vivo. Analysis reveals that free and cell-bound PSA are structurally similar, indicating that the poor immunogenicity of PSA is not due to major structural differences between cells and purified PSA. The 13 C linewidths of PSA on cells are 2 to 3 times larger than the corresponding ones in free PSA. The possible implications of the differences between free and on cell PSA are discussed. In addition, we demonstrate the suitability of the method for in vivo kinetic studies.carbohydrate structure ͉ isotopically labeled carbohydrates ͉ in vivo kinetics ͉ triple resonance NMR

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Immunologic Response of Man to Group B Meningococcal Polysaccharide Vaccines

Cited by 421 publications

References 14 publications

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

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

Meningococcal infection: --a review based upon papers presented at the 155th Meeting of the Pathological Society of Great Britain and Ireland at Southampton; 8 July, 1987

Extracellular structure of polysialic acid explored by on cell solution NMR

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