scholarly journals Antiidiotypic DNA vaccination induces serum bactericidal activity and protection against group B meningococci

2006 ◽  
Vol 203 (1) ◽  
pp. 111-118 ◽  
Author(s):  
Concetta Beninati ◽  
Angelina Midiri ◽  
Giuseppe Mancuso ◽  
Carmelo Biondo ◽  
Milena Arigò ◽  
...  
Keyword(s):  
Bactericidal Activity ◽  
Capsular Polysaccharide ◽  
Signal Sequence ◽  
Developed Countries ◽  
Single Chain ◽  
Serum Bactericidal Activity ◽  
Scfv Gene ◽  
Genes Encoding ◽  
Encapsulated Bacteria ◽  
Group B

No vaccine is available for preventing infections by serogroup B Neisseria meningitidis (MenB), which accounts for a major portion of meningococcal cases in developed countries, because of the poor immunogenicity of the capsular polysaccharide (CP) even after protein conjugation. We have previously induced anticapsular antibodies by immunization with a single chain variable fragment (scFv), which mimics a protective CP epitope. This surrogate antigen, however, was ineffective at inducing serum bactericidal activity, an accepted marker of protection in humans. Serum bactericidal activity was consistently achieved by immunizing mice with the scFv-encoding gene. Immunization with vectors without a secretory signal sequence before the scFv resulted in markedly higher bactericidal activity relative to those with such a sequence. The induced antibodies were capsule specific, as shown by complete inhibition of bactericidal activity by purified MenB CP and by resistance to killing of MenA or MenC. Moreover, these antibodies were predominantly of the IgG2a isotype, reflecting a T helper type 1 response. Administration of sera from scFv gene–vaccinated animals protected infant rats against MenB bacteremia. These data illustrate the potential of vaccination with genes encoding capsular mimics in providing protection against MenB and other encapsulated bacteria.

scholarly journals Immunogenicity and Safety Testing of a Group B Intranasal Meningococcal Native Outer Membrane Vesicle Vaccine

2002 ◽  
Vol 70 (2) ◽  
pp. 702-707 ◽  
Author(s):  
Rohit K. Katial ◽  
Brenda L. Brandt ◽  
Ellen E. Moran ◽  
Stephen Marks ◽  
Victor Agnello ◽  
...  
Keyword(s):  
Outer Membrane ◽  
Bactericidal Activity ◽  
Capsular Polysaccharide ◽  
Membrane Vesicle ◽  
Vaccine Dose ◽  
The United States ◽  
Outer Membrane Vesicle ◽  
Nasal Cytology ◽  
Group B ◽  
Antibody Secreting Cells

ABSTRACT The presently licensed meningococcal vaccine is a tetravalent capsular polysaccharide vaccine that induces immunity to serogroups A, C, Y, and W-135 but not to group B, which causes nearly half of the meningitis cases in the United States. The purpose of this study was to evaluate the safety and immunogenicity of an intranasal native outer membrane vesicle (NOMV) vaccine prepared from a capsule negative strain of group B of Neisseria meningitidis. In this study all volunteers received the same dose of vaccine, but we evaluated two different immunization schedules and the oropharyngeal and intranasal routes of vaccine delivery, assessed nasal cytology for cellular infiltration, and measured antibody-secreting cells (enzyme-linked immunospot assay [ELISPOT]) as an early marker for systemic immune response. Additionally, both intranasal and serum vaccine-specific antibodies were measured as well as serum bactericidal activity. Four groups with a total of 42 subjects were immunized on days 0, 28, and 56. Group 3 received an additional dose on day 7. Group 2 subjects were immunized both intranasally and oropharyngeally. Group 4 received a different lot of vaccine. All groups received approximately 1,200 μg of vaccine per subject. Patients were evaluated for side effects. The vaccine was well tolerated without evidence of inflammation on nasal cytology. The group receiving the extra vaccine dose showed the maximum increase in bactericidal activity. Thirty of 42 subjects demonstrated an increase in meningococcus-specific intranasal immunoglobulin A (IgA) titers, while 23 of 42 demonstrated an increase in specific IgG titers. The group receiving vaccine intranasally and oropharyngeally showed the highest rise in intranasal titers for both IgA and IgG. Groups 1, 3, and 4 showed a significant increase in antibody-secreting cells on ELISPOT. Eighteen of 42 volunteers demonstrated a fourfold or greater rise in bactericidal titers, with 81% showing an increase over baseline. We have demonstrated the immunogenicity and safety of a group B lipopolysaccharide-containing, intranasal, NOMV vaccine.

scholarly journals DNA Damage-Induced Neurodegeneration in Accelerated Ageing and Alzheimer’s Disease

2021 ◽  
Vol 22 (13) ◽  
pp. 6748
Author(s):  
Heling Wang ◽  
Sofie Lautrup ◽  
Domenica Caponio ◽  
Jianying Zhang ◽  
Evandro F. Fang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dna Repair ◽  
Werner Syndrome ◽  
Accelerated Ageing ◽  
Genes Encoding ◽  
Group A ◽  
Group B ◽  
Novel Therapeutic Strategies ◽  
Energy Deprivation

DNA repair ensures genomic stability to achieve healthy ageing, including cognitive maintenance. Mutations on genes encoding key DNA repair proteins can lead to diseases with accelerated ageing phenotypes. Some of these diseases are xeroderma pigmentosum group A (XPA, caused by mutation of XPA), Cockayne syndrome group A and group B (CSA, CSB, and are caused by mutations of CSA and CSB, respectively), ataxia-telangiectasia (A-T, caused by mutation of ATM), and Werner syndrome (WS, with most cases caused by mutations in WRN). Except for WS, a common trait of the aforementioned progerias is neurodegeneration. Evidence from studies using animal models and patient tissues suggests that the associated DNA repair deficiencies lead to depletion of cellular nicotinamide adenine dinucleotide (NAD+), resulting in impaired mitophagy, accumulation of damaged mitochondria, metabolic derailment, energy deprivation, and finally leading to neuronal dysfunction and loss. Intriguingly, these features are also observed in Alzheimer’s disease (AD), the most common type of dementia affecting more than 50 million individuals worldwide. Further studies on the mechanisms of the DNA repair deficient premature ageing diseases will help to unveil the mystery of ageing and may provide novel therapeutic strategies for AD.

scholarly journals Kinetics of the Natural, Humoral Immune Response to Salmonella enterica Serovar Typhi in Kathmandu, Nepal

2009 ◽  
Vol 16 (10) ◽  
pp. 1413-1419 ◽  
Author(s):  
Anoop S. Pulickal ◽  
Samir Gautam ◽  
Elizabeth A. Clutterbuck ◽  
Stephen Thorson ◽  
Buddha Basynat ◽  
...  
Keyword(s):  
Bactericidal Activity ◽  
Salmonella Enterica ◽  
Capsular Polysaccharide ◽  
Geometric Mean ◽  
Public Health Problem ◽  
Major Public Health Problem ◽  
Natural Immunity ◽  
Humoral Immune ◽  
Bactericidal Antibody ◽  
Stratified Sample

ABSTRACT Typhoid fever is a major public health problem in developing countries, conservatively estimated to occur in 17 million cases and be responsible for 200,000 deaths annually. We investigated the acquisition of natural immunity to Salmonella enterica serovar Typhi in a region where typhoid is endemic by testing sera from an age-stratified sample of 210 healthy participants in Kathmandu, Nepal, for bactericidal activity toward S. Typhi and for anti-Vi capsular polysaccharide antibodies. Bactericidal titers in children were significantly lower than those in newborns and adults (P < 0.0001). Anti-S. Typhi bactericidal geometric mean titers were age dependent, increasing 10-fold during childhood. Anti-Vi polysaccharide antibody geometric mean concentrations were also lower in children than in adults. Data presented here indicate the possibility of a relationship between low levels of bactericidal activity toward S. Typhi in serum and susceptibility to disease, as observed for other polysaccharide-encapsulated bacteria. Bactericidal antibody may be a marker of protective immunity against S. Typhi.

scholarly journals The Yeast Signal Sequence Trap Identifies Secreted Proteins of the Hemibiotrophic Corn Pathogen Colletotrichum graminicola

2008 ◽  
Vol 21 (10) ◽  
pp. 1325-1336 ◽  
Author(s):  
Jorrit-Jan Krijger ◽  
Ralf Horbach ◽  
Michael Behr ◽  
Patrick Schweizer ◽  
Holger B. Deising ◽  
...  
Keyword(s):  
Cell Walls ◽  
Leaf Extract ◽  
Signal Sequence ◽  
Stem Rot ◽  
Colletotrichum Graminicola ◽  
In Planta ◽  
Chain Reaction ◽  
Genes Encoding ◽  
Polymerase Chain

The hemibiotroph Colletotrichum graminicola is the causal agent of stem rot and leaf anthracnose on Zea mays. Following penetration of epidermal cells, the fungus enters a short biotrophic phase, followed by a destructive necrotrophic phase of pathogenesis. During both phases, secreted fungal proteins are supposed to determine progress and success of the infection. To identify genes encoding such proteins, we constructed a yeast signal sequence trap (YSST) cDNA-library from RNA extracted from mycelium grown in vitro on corn cell walls and leaf extract. Of the 103 identified unigenes, 50 showed significant similarities to genes with a reported function, 25 sequences were similar to genes without a known function, and 28 sequences showed no similarity to entries in the databases. Macroarray hybridization and quantitative reverse-transcriptase polymerase chain reaction confirmed that most genes identified by the YSST screen are expressed in planta. Other than some genes that were constantly expressed, a larger set showed peaks of transcript abundances at specific phases of pathogenesis. Another set exhibited biphasic expression with peaks at the biotrophic and necrotrophic phase. Transcript analyses of in vitro-grown cultures revealed that several of the genes identified by the YSST screen were induced by the addition of corn leaf components, indicating that host-derived factors may have mimicked the host milieu.

Initial Studies of the Molecular Basis of Peptide Mimicry of Group B Streptococcal Type III Capsular Polysaccharide

2001 ◽  
Vol 20 (2) ◽  
pp. 221-227 ◽  
Author(s):  
Seth H. Pincus ◽  
Stephen R. Lepage ◽  
Robert F. Jung ◽  
Jennifer G. Massey ◽  
Mahesh Jaseja
Keyword(s):  
Molecular Basis ◽  
Capsular Polysaccharide ◽  
Type Iii ◽  
Peptide Mimicry ◽  
Group B
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