For 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.

Many drugs can’t do it, but GBS can!

Bacterial meningitis is one of the leading causes of death and disability among childrens.  Meningits occurs when bacteria cross blood brain barrier  (BBB) after interacting with human Brain microvascular endothelial cells (hBMECs) . Although these cells are exhibiting tight junctions and lacking pinocytosis, some bacteria could cross it and this demonstrates an interplay between host cells and some bacterial factors.

Scientists at USCD school of medicine used a process involving generating and screening of many group B streptococcus (GBS)  in tissue culture model of human BBB (consisting of immortalised hBMECs) . This culture maintained the normal function of human BBB.

 They identified a gene called iagA gene encoding for a glycosyltransferase. A predicted product of the iagA glycosyltransferase is the glycolipid  diglycosyldiacylglycerol involved in anchoring lipoteichoic acid (LTA) and consequently, enhances BBB invasion.

Allelic replacement of the iagA gene,so that the resulting mutants are lacking the gene, shed LTA into the media. As a result, mice infected with mutant gene exhibited less mortality rate -up to 90 percent- compared to wild-type infected mice. Mutant-type infected mice developed bacteremia  as WT which proves the fact that iagA gene plays the central role in BBB invasion without significantly affecting adhesion or blood survival.

Since bacterial meningitis may cause infected children death or many complications as permanent cognitive deficits, blindness, deafness or seizures, an early treatment may help reduce high rates of death and disability.

This early treatment may be much more easily designed after these findings by blocking LTA anchoring on bacterial cell surface.This will help preventing meningitis even though bacteriemia has taken place.

The journal of clinical investigation has the full story.