Posts Tagged “vaccinology”

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Aetiology and epidemiology

Meninigococcal meninigits and septicemia are devastating diseases caused by Neissieria meningitidis. Although infants and young children are the most susceptible to the disease, adults are also affected but with less incidence. N.meningitidis is a gram negative capsulated bacterium that has been classified into five serogroups (A, B, C, Y, W135)  based on their polysaccharide capsule.

The challenge

Over forty years, developing a vaccine against this dangerous bacterium proceeded with little success. In 1960, the purified polysaccharide antigens were used to develop a vaccine against four groups (A, C, Y, W135) . Unfortunately, this vaccine was highly effective in adults but didn’t give protection to young infants and children who represent the age group most susceptible to the disease. Another challenge is that this vaccine didn’t show success against serogroup B (known as:MenB).

More attempts to overcome the new challenge

Using capsular polysaccharide antigen, as a vaccine against MenB, wasn’t a very good idea. This is due to the fact that MenB capsular polysaccharide is highly similar (nearly identical) to N-acetyl neuraminic acid which is widely distributed in human tissue and that means it is a self antigen. The new vaccine was poorly immunogenic (and thus provide poor protection) and also it might elicit auto-antibodies.

As scientists never give up, they switched into the new trend in vaccinology: Reverse vaccinology. Due to the formerly mentioned, N.meningitidis was expected to be a very promising candidate for reverse vaccinology.

RV provides help

Using in silico technique (computational biology), the genome sequence was fed into a computer, 570 proteins of the bacterium surface were predicted. Going for more refinement, only 350 of these proteins were successfully expressed in E.coli and and used to immunise mice. The sera assays allowed the identification of certain proteins that elicit bactericidal antibodies and surprisingly, were conservative among different strains and this meets the criteria for a good vaccine.

Going forward

As research is proceeding to deprive our pathogen from enjoying its life inside our bodies, this work suggested further research of other pathogens such as: Streptococcus pneumoniae, Chlamydia pneumoniae, Bascillus anthracis, T.B and group B Streptococcus. 


A universal vaccine against serogroup B meningococcus.

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A shematic diagram comparing conventional vaccinology to reverse vaccinologyFor many decades, conventional vaccinology has faced many obstacles. One major problem is that among several antigens of the microbe, you have to identify the most immunogenic (and thus protective) antigens (such as virulent factors, toxins, surface-associated proteins, etc.) suitable for vaccine development. This process is very fastidious and costs a lot as it relies mainly on traditional biochemical and microbiological methods. As a summary, it is carried out as following:

  • Firstly, you have to cultivate the microbe and harvest proteins.
  • Then you have to identify the antigens one by one.
  • After that you can pass to vaccine development stage.

Introducing genomics has greatly contributed to providing a new impulse to vaccinology field. The major role it plays is in the antigen discovery stage. As the genome sequence of many microbes has been identified, the integration between the sequence, proteomics and microarray has introduced what is called “reverse vaccinology” . Reverse vaccinology (RV) means to identify and characterise the antigen using bioinformatics. In RV, you start from the genome and not from the pathogen itself i.e.  you start from the opposite direction, that’s why it is called “reverse”.

RV will provide solutions to some problems that usually come up during vaccine development as:

  • It will provide fast access to almost all antigens including:less common antigens and antigens not expressed in vitro.
  • It represents a new approach for non culturable microorganisms.

On the other hand, the major disadvantage of RV is that it cannot be applied to non-proteinaceous antigens such as lipopolysaccharides and glycolipids.

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To be frank, I was really underestimating these bacteria. Streptococcus iniae, bacteria bothering fish, what’s the big deal? But when I read that it cause them meningoencephalitis due to systemic dissemination resulting in death, it made me sad. They’re fish, you know, they don’t deserve such destiny. (We can’t say that about eating them, right?) Back to scientific details, S. iniae was isolated from Amazon dolphins (Inia) but it has a very wide host range, it can infect fresh & saltwater species like salmon, yellowtail & hybrid striped bass (HSB). It also can infect immunocompromised as well as elders from humans.Fish - Cartoon

S. iniae are beta-hemolytic streptococci, they have M protein (present in cell membrane) then the capsular polysaccharide which interfere with phagocytosis. They also have phosphoglucomutase which make their cell wall rigid & resistant to peptide antimicrobials, besides their streptolysin S. I’ve to tell you this, this iniae is a walking disaster, just like the human version S. pyogenes.

So what scientists tell us this time? Thanks to 454 pyrosequencing & bioinformatics, they identified extra virulence factors of S. iniae. Regulations in S. iniae are done through a Mga-like Mgx loci (multiple gene regulator of group A streptococci). It regulates the virulence factors. It’s used to be known that M-protein is a component of that Mga. This time, discovery of extra components takes place, the M-like surface protein (simA) & C5a peptidase (scpI). A word about scpI, its role is to inactivate C5a (the complement component) to hinder the complement reaction & also has a role in adhesion to epithelial cells.

Actually they’re looking forward to using the mutant delta-simA as a live attenuated vaccine against S. iniae. (Vaccine for fish?) They made mutations in both C5a-like peptidase & simA, apparently simA had the leading role in the virulence of the studied strain of S. iniae. So a new approach of vaccination will be developed instead of the old M protein vaccination strategy which requires multimeric vaccination (to provide protection against several serotypes) & showes autoimmune response. Unlike the ordinary M protein vaccination, vaccination with the mutant delta-simA will result in development of humoral as well as cell-mediated immunity.

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Fish – Cartoon:

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