scholarly journals Serum Antibody Responses in Ethiopian Meningitis Patients Infected with Neisseria meningitidis Serogroup A Sequence Type 7

2007 ◽  
Vol 14 (4) ◽  
pp. 451-463 ◽  
Author(s):  
Gunnstein Norheim ◽  
Abraham Aseffa ◽  
Mohammed Ahmed Yassin ◽  
Getahun Mengistu ◽  
Afework Kassu ◽  
...  
Keyword(s):  
Membrane Proteins ◽  
Outer Membrane ◽  
Acute Phase ◽  
Outer Membrane Proteins ◽  
Serum Antibody ◽  
Outer Membrane Vesicles ◽  
Sequence Type ◽  
Enzyme Linked Immunosorbent Assay ◽  
Human Complement ◽  
Convalescent Phase

ABSTRACT To elucidate critical components of protective immune responses induced during the natural course of serogroup A meningococcal disease, we studied acute-, early-convalescent-, and late-convalescent-phase sera from Ethiopian patients during outbreaks in 2002 to 2003. Sera were obtained from laboratory-confirmed patients positive for serogroup A sequence type 7 (ST-7) meningococci (A:4/21:P1.20,9) (n = 71) and from Ethiopian controls (n = 113). The sera were analyzed using an enzyme-linked immunosorbent assay to measure levels of immunoglobulin G (IgG) against serogroup A polysaccharide (APS) and outer membrane vesicles (OMVs) and for serum bactericidal activity (SBA) using both rabbit and human complement sources. Despite relatively high SBA titers and high levels of IgG against APS and OMVs in acute-phase patient sera, significant increases were seen in the early convalescent phase. Antibody concentrations returned to acute-phase levels in the late convalescent phase. Considering all patients' sera, a significant but low correlation (r = 0.46) was observed between SBA with rabbit complement (rSBA) using an ST-5 reference strain and SBA with human complement (hSBA) using an ST-7 strain from Ethiopia. While rSBA demonstrated a significant linear relation with IgG against APS, hSBA demonstrated significant linear relationships with IgG against both APS and OMV. This study indicates that antibodies against both outer membrane proteins and APS may be important in providing the protection induced during disease, as measured by hSBA. Therefore, outer membrane proteins could also have a role as components of future meningococcal vaccines for the African meningitis belt.

scholarly journals Immunization withSalmonella entericaSerovar Typhimurium-Derived Outer Membrane Vesicles Delivering the Pneumococcal Protein PspA Confers Protection against Challenge withStreptococcus pneumoniae

2010 ◽  
Vol 79 (2) ◽  
pp. 887-894 ◽  
Author(s):  
Maneesha Muralinath ◽  
Meta J. Kuehn ◽  
Kenneth L. Roland ◽  
Roy Curtiss
Keyword(s):  
Membrane Proteins ◽  
Outer Membrane ◽  
Outer Membrane Proteins ◽  
Lethal Dose ◽  
Serum Antibody ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Gram Negative Bacteria ◽  
Vesicle Preparation ◽  
Serovar Typhimurium

ABSTRACTGram-negative bacteria produce outer membrane vesicles (OMVs) that serve a variety of functions related to survival and pathogenicity. Periplasmic and outer membrane proteins are naturally captured during vesicle formation. This property has been exploited as a method to derive immunogenic vesicle preparations for use as vaccines. In this work, we constructed aSalmonella entericaserovar Typhimurium strain that synthesized a derivative of the pneumococcal protein PspA engineered to be secreted into the periplasmic space. Vesicles isolated from this strain contained PspA in the lumen. Mice intranasally immunized with the vesicle preparation developed serum antibody responses against vesicle components that included PspA andSalmonella-derived lipopolysaccharide and outer membrane proteins, while no detectable responses developed in mice immunized with an equivalent dose of purified PspA. Mucosal IgA responses developed against theSalmonellacomponents, while the response to PspA was less apparent in most mice. Mice immunized with the vesicle preparation were completely protected against a 10× 50% lethal dose (LD50) challenge ofStreptococcus pneumoniaeand significantly protected against a 200× LD50challenge, while control mice immunized with purified PspA or empty vesicles were not protected. These results establish that vesicles can be used to mucosally deliver an antigen from a Gram-positive organism and induce a protective immune response.

scholarly journals Human Opsonins Induced during Meningococcal Disease Recognize Outer Membrane Proteins PorA and PorB

1999 ◽  
Vol 67 (5) ◽  
pp. 2552-2560 ◽  
Author(s):  
A. K. Lehmann ◽  
A. Halstensen ◽  
I. S. Aaberge ◽  
J. Holst ◽  
T. E. Michaelsen ◽  
...  
Keyword(s):  
Outer Membrane ◽  
Meningococcal Disease ◽  
Oxidative Burst ◽  
Outer Membrane Proteins ◽  
Outer Membrane Vesicles ◽  
Enzyme Linked Immunosorbent Assay ◽  
Membrane Structures ◽  
Human Patient ◽  
Convalescent Phase

ABSTRACT Human opsonins directed against specific meningococcal outer membrane structures in sera obtained during meningococcal disease were quantified with a recently developed antigen-specific, opsonin-dependent phagocytosis and oxidative burst assay. Outer membrane vesicles (OMVs) and PorA (class 1) and PorB (class 3) proteins purified from mutants of the same strain (44/76; B:15:P1.7.16) were adsorbed to fluorescent beads, opsonized with acute- and convalescent-phase sera from 40 patients with meningococcal disease, and exposed to human leukocytes. Flow cytometric quantitation of the resulting leukocyte phagocytosis products (PPs) demonstrated that disease-induced serum opsonins recognized meningococcal OMV components and both porins. The PPPorA and PPPorB values induced by convalescent-phase sera correlated positively with the PPOMV values. However, the PPPorB values were higher than the PPPorA values in convalescent-phase sera (medians [ranges] of 754 [17 to 1,057] and 107 [4 to 458], respectively) (P < 0.0001) and correlated positively with higher levels of immunoglobulin G against PorB than against PorA as evaluated by enzyme-linked immunosorbent assay. Extensive individual variations in the anti-OMV and antiporin serum opsonic activities between patients infected by serotypes and serosubtypes homologous and heterologous to the target antigens were observed. Simultaneously measured oxidative burst activity correlated with the opsonophagocytosis, an indication that both of these important steps in the in vitro phagocytic elimination of meningococci are initiated by opsonins directed against OMV components, including PorA and PorB. In conclusion, human patient opsonins against meningococcal OMV components and in particular PorB epitopes were identified by this new method, which might facilitate selection of opsonin-inducing meningococcal antigens for inclusion in future vaccines.

The search forBrachyspiraouter membrane proteins that interact with the host

2001 ◽  
Vol 2 (1) ◽  
pp. 19-30 ◽  
Author(s):  
Darren J. Trott ◽  
David P. Alt ◽  
Richard L. Zuerner ◽  
Michael J. Wannemuehler ◽  
Thaddeus B. Stanton
Keyword(s):  
Membrane Proteins ◽  
Outer Membrane ◽  
Membrane Vesicle ◽  
Outer Membrane Proteins ◽  
Indirect Evidence ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Surface Proteins ◽  
Brachyspira Pilosicoli ◽  
Variable Surface

AbstractLittle is known about the outer membrane structure ofBrachyspira hyodysenteriae and Brachyspira pilosicolior the role of outer membrane proteins (OMPs) in host colonization and the development of disease. The isolation of outer membrane vesicles fromB. hyodysenteriaehas confirmed that cholesterol is a significant outer membrane constituent and that it may impart unique characteristics to the lipid bilayer structure, including a reduced density. Unique proteins that have been identified in theB. hyodysenteriaeouter membrane include the variable surface proteins (Vsp) and lipoproteins such as SmpA and BmpB. While the function of these proteins remains to be determined, there is indirect evidence to suggest that they may be involved in immune evasion. These data may explain the ability of the organism to initiate chronic infection. OMPs may be responsible for the unique attachment ofB. pilosicolito colonic epithelial cells; however, the onlyB. pilosicoliOMPs that have been identified to date are involved in metabolism. In order to identify furtherB. pilosicoliOMPs we have isolated membrane vesicle fractions from porcine strain 95–1000 by osmotic lysis and isopycnic centrifugation. The fractions were free of contamination by cytoplasm and fla-gella and contained outer membrane. Inner membrane contamination was minimal but could not be completely excluded. An abundant 45-kDa, heat-modifiable protein was shown to have significant homology withB. hyodysenteriaeVsp, and monoclonal antibodies were produced that reacted with fiveB. pilosicoli-specificmembrane protein epitopes. The first of these proteins to be characterized is a unique surface-exposed lipoprotein.

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