There is a bacterium called Streptococcus pneumoniae . It comes in at least a hundred different forms, or serotypes, and lives in the tissue lining our nose and throat. S. pneumoniae is normally harmless . But when your body’s immune system becomes weaker, for example when you have a viral fever, these bacteria may invade your lungs and cause pneumonia, your brain and spinal cord to cause meningitis, and your bloodstream to cause sepsis.
Recently, a team of British scientists reported an important first step in this direction. To increase coverage, scientists need to include additional serotype-specific capsular polysaccharides in the vaccine. And covering all the serotypes in a single shot would be extremely challenging, not to mention extremely expensive as well. They did two things: first, they switched the polysaccharide with proteins and, second, they adopted an approach called reverse vaccinology. To help boost the effects as well as the durability of the immune response, scientists have linked the polysaccharides to a carrier protein. Such vaccines are known as pneumococcal conjugate vaccines (PCVs). Typical examples include PCV10 and PCV14; the numerals denote the number of serotypes included. When these vaccines target and eliminate some serotypes of S. pneumoniae , it also opens the door for other serotypes to mount an infection. These non-vaccine serotypes also face less biological competition for space and resources, so they multiply and eventually replace the vaccine-targeted serotypes, rendering the vaccines obsolete. Thus, scientists are looking for a universal pneumococcal vaccine that can target all serotypes and prevent these outcomes, which keep the threat of pneumonia, meningitis, and other pneumococcal diseases alive in the population. Reverse vaccinology starts from the germ’s genome to identify proteins that can be included in vaccines. The approach completely bypassed the need to culture the germs in large bioreactors and purify molecular components from them to make the vaccine. The scientists deployed extensive computational analysis using an arsenal of bioinformatic tools to analyse these sequences. The team shortlisted some candidates and further whittled the list down based on their predicted shapes and stability. From this, the team picked three candidate genes.
They were: zinc metalloprotease B (Z), pneumococcal adherence virulence factor A (P), and a protein which the scientists designated YfhO-like (Y) due to its similarity to another bacterial protein. And the current crop of pneumococcal vaccines protect against only a subset of the 100-odd serotypes. Scientists demonstrated an example of this in the recent COVID-19 pandemic: once the virus’s genome was sequenced in early 2020, scientists around the world could analyse it and zero in on the spike-protein gene to make COVID-19 vaccines. The S. pneumoniae genome encodes more than 2,000 genes. Of them, around 1,300 are common across serotypes. The genomic data of more than 20,000 S. pneumoniae isolates across nearly a hundred serotypes are also available in the public domain.
