scholarly journals Specificity of the Immune Response to a Modified Group B Meningococcal Polysaccharide Conjugate Vaccine

2006 ◽  
Vol 14 (1) ◽  
pp. 106-109 ◽  
Author(s):  
Samuel Moore ◽  
Esmé K. Farley ◽  
Peter C. Fusco ◽  
Francis Michon

ABSTRACT Antibodies to a modified group B meningococcal polysaccharide vaccine were examined for antigenic and functional specificities. Bactericidal determinants were investigated by using immunoaffinity columns and competitive inhibition of bactericidal activity in an in vitro killing assay. We conclude that nearly all of the vaccine-induced bactericidal activity is specific for the native polysaccharide.

2002 ◽  
Vol 80 (8) ◽  
pp. 1055-1063 ◽  
Author(s):  
Robert A Pon ◽  
Nam Huan Khieu ◽  
Qing-Ling Yang ◽  
Jean-Robert Brisson ◽  
Harold J Jennings

The capsular polysaccharide of E. coli K92 (K92P) contains elements in common with the capsular polysaccharides of both groups B and C N. meningitidis, and may therefore form the basis of a bivalent vaccine. In an attempt to augment the cross-protective immune response to group B meningococci, the N-acetyl groups of the K92P were replaced by N-propionyl groups (NPrK92P) and conjugated to protein. This strategy had previously been applied with success to the poorly immunogenic capsular polysaccharide of group B meningococcus (GBMP), and the bactericidal epitope was found to be exclusively mimicked by extended helical segments of the NPrGBMP. The NPrK92P-conjugate, in relation to a K92P-conjugate, failed to enhance the response to GBMP but did generate a measurable response to NPrGBMP, but only at the expense of a greatly reduced GCMP response. Despite the presence of an immune response to NPrGBMP, the anti-NPrK92 serum was not bactericidal. Competitive inhibition studies with NPrGBMP oligosaccharides suggested the NPrK92 antibodies could not cross-react with the protective epitope on group B meningococci, as defined by extended helical segments of the NPrGBMP, but only recognized short non-bactericidal NPrGBMP epitopes. This hypothesis was supported from the conformational and molecular dynamics studies of the K92P, which demonstrated a lack of extended conformations that resemble the GBMP extended epitope. Indeed, the conformational properties of the K92P more closely resembled those of the GCMP, thereby explaining the observed moderate cross-protection of the K92P antiserum towards group C meningococci. Thus, on the basis of these results, it can be concluded that K92P, regardless of N-propionyl modification, will not serve as an effective single vaccine component against both groups B and C meningococci.Key words: conjugate vaccine, Neisseria meningitidis, polysialic acid, NMR, molecular dynamics.


Vaccine ◽  
2008 ◽  
Vol 26 (35) ◽  
pp. 4557-4562 ◽  
Author(s):  
Siggeir F. Brynjolfsson ◽  
Stefania P. Bjarnarson ◽  
Elena Mori ◽  
Giuseppe Del Giudice ◽  
Ingileif Jonsdottir

1967 ◽  
Vol 126 (5) ◽  
pp. 795-818 ◽  
Author(s):  
Richard B. Roberts

The interaction in vitro between group B meningococci and rabbit polymorphonuclear leukocytes has been described. Phagocytosis did not occur in the presence of normal rabbit serum. Antiserum collected 12–21 days following one subcutaneous inoculation of living log phase meningococci exhibited opsonic activity with type specificity; this opsonic action depended on both heat-labile and heat-stable factors. Following ingestion by granulocytes, meningococci were rapidly killed. These studies suggest that group B meningococcal strains contain specific antiphagocytic surface factors of an as yet unknown chemical nature. Antisera obtained 4 or more wk after immunization showed bactericidal activity with the same type specificity as opsonic activity. This bactericidal activity was also lost after heating and restored by the addition of normal serum. Further studies on opsonins and bactericidins for meningococci may shed light on virulence factors in these microorganisms, and may prove useful for a more precise classification of meningococci according to type rather than group specificity.


Glycobiology ◽  
2020 ◽  
Author(s):  
Minhal Abidi ◽  
Abdul Rouf Mir ◽  
Farzana Khan ◽  
Asif Ali ◽  
Moin Uddin

Abstract This study elucidates the immunological implications of methylglyoxal (MGO) modified LDL in diabetes type 2 patients (T2DM). Under in-vitro modifications, MGO altered the tertiary structure of LDL. TNBS and phenanthrenequinone assays confirmed lysine and arginine residues as main targets of MGO in LDL. HPLC and LCMS studies confirmed the generation of Nϵ-(carboxymethyl) lysine in the modified protein. Comet assay showing increased tail length of DNA in lymphocytes inferred the cytotoxicity of MGO-LDL. The easy penetration of MGO-LDL into the nucleus is possibly a consequence of its reduced size, post-modification, as observed from the studies on hydrodynamic radii studies in DLS experiments. MGO-LDL was found to be more immunogenic, as compared to native LDL, in immunological studies conducted on experimental rabbits. Our results reflect the presence of neo-antigenic determinants on modified LDL. Competitive inhibition ELISA suggested the presence of neo-epitopes with marked immunogenicity eliciting specific immune response. Binding studies on purified IgG confirmed the enhanced and specific immunogenicity of MGO-LDL. Studies on interaction of MGO-LDL with the circulating auto-antibodies from T2DM patients showed high affinity of serum-antibodies towards MGO-LDL. This study suggests a potent role of glycoxidatively modified LDL in the generation of auto-immune response in T2DM patients.


Vaccine ◽  
2014 ◽  
Vol 32 (3) ◽  
pp. 417-424 ◽  
Author(s):  
Sigurveig Th. Sigurdardottir ◽  
Kimberly J. Center ◽  
Katrin Davidsdottir ◽  
Vilhjalmur A. Arason ◽  
Bjorn Hjalmarsson ◽  
...  

1988 ◽  
Vol 65 (1) ◽  
pp. 137-145 ◽  
Author(s):  
M. P. Sherman ◽  
J. B. D'Ambola ◽  
E. E. Aeberhard ◽  
C. T. Barrett

Because in vitro studies indicate that pulmonary alveolar macrophages (PAM's) filled with phospholipid vesicles have depressed microbicidal capacity, we tested the intrapulmonary bactericidal activity of newborn PAM's after surfactant treatment. Term newborn rabbits received intratracheally either homologous surfactant or one of two artificial phospholipid vesicle preparations followed by pulmonary aerosol infection with group B streptococci (GBS). Four hours after lung infection, phagocytic killing of GBS was reduced by 70-90% in animals treated with the homologous and one of the artificial surfactants compared with untreated animals or animals that received intrapulmonary injections of the surfactant vehicle (P less than 0.02). The other artificial phospholipid preparation decreased intrapulmonary inactivation of GBS by 30-40% compared with the controls. The phospholipid vesicles in the three preparations were avidly ingested and processed by newborn PAM's. The diminished in vivo killing of GBS was not attributed to decreased viability or phagocytic behavior of the PAM's toward GBS. The bactericidal defect that was evident in the newborn PAM's appeared related to the uptake of large phospholipid vesicles in the preparations rather than to the phospholipid content of the surfactants themselves. When in vitro conditions that stimulated the alveolar environment were used, the natural surfactant preparation promoted GBS proliferation, whereas the artificial preparations did not. Our findings indicate that surfactant administration reduces the bactericidal activity of neonatal PAM's. We conclude that additional investigations are needed to ascertain the effect of surfactant replacement therapy on lost defenses of the lung.


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