Genomic Identification of vaccine candidates for streptococcus pneu...

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Streptococcus pneumonia, gram positive pathgen that cause community-acquired pneumonia, sepsis, meningitis, otitis media and some noninvasive diseases such as ear infections and bronchitis.. Like other respiratory pathogens, the pneumococcus is primarily a commensal, colonizing the nasopharynx in 5 to 10% of healthy adults and 20 to 40% of healthy children. Sometimes, however, the bacteria invade the lungs (where they cause pneumonia), the bloodstream (where they cause bacteremia), or the covering of the brain (where they cause meningitis).Invasive pneumococcal diseases (INDs) primarily occurs at the extremes of age, in young infants, elderly peoples and patients with chronic conditions such as diabetes and alcoholism. IPD is marked by progression of the bacteria from the nasopharynx to sterile sites, such as the lungs, blood, and brain. Worldwide, it is estimated that S. pneumoniae is responsible for 15 cases of IPD per 100,000 persons per year and over a million deaths annually.

For over a century, vaccines were developed according to Pasteur's principles of isolating, inactivating and injecting the causative agent of an infectious disease. The availability of a complete microbial genome sequence in 1995 marked the beginning of a genomic era that has allowed to change the paradigm and approach vaccine development starting from genomic information, a process named "reverse vaccinology". This can be considered as one of the most powerful examples of how genomic information can be used to develop therapeutic interventions, which were difficult or impossible to tackle with conventional approaches.

The hundreds of bacterial genome sequences available together with advances in bioinformatics and the development of new experimental proteomic tools are revolutionizing the vaccinology field. The merge of stringent in silico criteria and different experimental approaches is allowing a more targeted strategy to obtain a restricted and prioritized list of potential antigens for testing in immunogenicity assays, reducing the time and the cost of novel protein vaccine formulations.

The 2,160,837-base pair genome sequence of Streptococcus pneumonia are isolated that contains 2236 predicted coding regions; of these, 1440 (64%) were assigned a biological role. Approximately 5% of the genome is composed of insertion sequences that may contribute to genome rearrangements through uptake of foreign DNA.

In this the entire genome sequence of a virulent strain were used to identify vaccine candidates. A total of 350 candidate antigens were expressed in Escherichia coli, purified, and used to immunize mice. The sera allowed the identification of proteins that are surface exposed, that are conserved in sequence across a range of strains, and that induce a bactericidal antibody response, a property known to correlate with vaccine efficacy in humans.

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Streptococcus pneumonia, gram positive pathgen that cause community-acquired pneumonia, sepsis, meningitis, otitis media and some noninvasive diseases such as ear infections and bronchitis.. Like other respiratory pathogens, the pneumococcus is primarily a commensal, colonizing the nasopharynx in 5 to 10% of healthy adults and 20 to 40% of healthy children. Sometimes, however, the bacteria invade the lungs (where they cause pneumonia), the bloodstream (where they cause bacteremia), or the covering of the brain (where they cause meningitis).Invasive pneumococcal diseases (INDs) primarily occurs at the extremes of age, in young infants, elderly peoples and patients with chronic conditions such as diabetes and alcoholism. IPD is marked by progression of the bacteria from the nasopharynx to sterile sites, such as the lungs, blood, and brain. Worldwide, it is estimated that S. pneumoniae is responsible for 15 cases of IPD per 100,000 persons per year and over a million deaths annually.

The 2,160,837-base pair genome sequence of Streptococcus pneumonia are isolated that contains 2236 predicted coding regions; of these, 1440 (64%) were assigned a biological role. Approximately 5% of the genome is composed of insertion sequences that may contribute to genome rearrangements through uptake of foreign DNA.

Introduction:-

Different Biochemical, serological and microbiological methods have been used to dissect pathogens and identify the components useful for vaccine development. Although successful in many cases, this approach is time-consuming and fails when the pathogens cannot be cultivated in vitro, or when the most abundant antigens are variable in sequence. Now genomic approaches allow for the design of vaccines starting from the prediction of all antigens in silico, independently of their abundance and without the need to grow the microorganism in vitro. This allows vaccine development using non-conventional antigens and exploiting non-conventional arms of the immune system. Many vaccines impossible to develop so far will become a reality. Since the process of vaccine discovery starts in silico using the genetic information rather than the pathogen itself, this novel process named "reverse vaccinology".

Reverse vaccinology is an improvement on vaccinology, pioneered by Rino Rappuoli and first used against meningococcus. Since then, it has been used on several other organisms[Which has been successfully applied in the last few years, has revolutionized the approach to vaccine research. The Neisseria meningitidis serogroup B project, the first example of Reverse Vaccinology, as well as the application of this strategy to develop novel vaccines against other human pathogens are discussed.

Genomic sequencing has provided a tremendous amount of information that can be useful in vaccine target identification. The sheer volume of information available necessitates the use of new research disciplines and techniques. Using bioinformatics, researchers sift through available data to identify appropriate candidates for biological analysis.

Although vaccines against Streptococcus pneumoniae are available, they cover only a restricted number of the more than 90 known serotypes and it is essential to pursue new vaccines for distribution in countries with the highest medical need for an effective vaccine against the pathogen. Intercell's novel vaccine candidate is composed of highly conserved proteins of Streptococcus pneumoniae that have the potential to protect against all serotypes.

Streptococcus pneumoniae, or Pneumococcus, is a very common bacterial infection in both industrialized and developing countries. In particular, young children and the elderly represent high-risk populations of developing pneumococcal infections. According to the WHO, the bacterium kills up to one million children under the age of five years each year worldwide.

State of the art:-

Genes and protein data for human and for the sequenced Streptococcus pneumoniae can be download from NCBI. P-CLASSIFIER apply to predict the subcellular locations of proteins in Streptococcus pneumoniae strain. Signal peptide prediction can carry out using SignalP 3.0. α-Helix transmembrane topology prediction will carried out using TMHMM. BOMP will use to predict β-barrel outer membrane proteins. Putative lipoproteins can be predict by SpLiP.

Objectsives-

Identification of T-Cell epitopes.

Identification of B-Cell epitopes.

Review of Literature:-

Streptococcus pneumoniae is a causative agent for community acquired pneumonia, bacteremia, acute otitis media, and meningitis of which 90 serotypes are known. Two types of pneumococcal polysaccharide vaccine and pneumococcal conjugate vaccine are commonly using vaccines against Streptococcus pneumoniae. These vaccines elicit protective antibodies against the infection of serotypes that are included in the vaccine. Capsular polysaccharides (CPSs) induce production of protective antibodies; however, it is not feasible to develop CPS-based vaccines that cover all of the 90 disease-causing serotypes.

Recent emergence of multi-drug resistant clinical isolates prompts the need of effective vaccine for the prevention of disease. To broaden the protection, the use of pneumococcal proteins will be a feasible and preferable alternative.

State of the art:-

Genes and protein data for human and for the sequenced Streptococcus pneumoniae can be download from NCBI.

P-CLASSIFIER apply to predict the subcellular locations of proteins in Streptococcus pneumoniae strain.

Signal peptide prediction can carry out using SignalP 3.0.

α-Helix transmembrane topology prediction will carried out using TMHMM.

BOMP will use to predict β-barrel outer membrane proteins.

Putative lipoproteins can be predict by SpLiP.

Methodology:-

Significance:-

The basic idea behind Reverse Vaccinology is that an entire pathogenic genome can be screened using bioinformatics approaches to find genes. Next, those genes are filtered for desirable attributes that would make good vaccine targets such as outer membrane proteins. Those proteins then undergo normal wet lab testing for immune responses.

The major advantage for Reverse Vaccinology is finding vaccine targets quickly and efficiently. The downside is that only proteins can be targeted using this process. Normal vaccinology approaches can find other biomolecular targets such as polysaccharides.

This reduces the time required for the identification of candidate vaccines and provides new solutions for those vaccines which have been difficult or impossible to develop and also demonstrate how new types of information obtained from genetic typing and antigen-based serological typing can support the vaccine development phase as well as the continued clinical surveillance needed upon the introduction of a new vaccine into the field.

Reverse vaccinology offers the ability to undertake a rapid and comprehensive assessment of a micro-organism's surface protein repertoire, and has advantages over conventional approaches to identifying candidate antigens. Despite the advantages of the approach, development in conventional areas of vaccinology remains important to support the process of producing vaccines from genome-derived antigens.

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