Streptococcus pneumoniae lives harmlessly in our nose and throat, but when immunity dips after viral fever, it invades lungs, brain and blood - causing pneumonia, meningitis and sepsis. These pneumococcal diseases are vaccine-preventable, yet our vaccines protect only against a fraction.
The bug has at least 100 serotypes, each with unique sugary capsule polysaccharide. Current vaccines - Pneumovax 23 is pure polysaccharide mix, weak and short-lived; Prevnar PCV10 and PCV13 link polysaccharides to carrier proteins for stronger immunity - target only a subset. When they kill those serotypes, non-vaccine serotypes fill the gap, multiplying and replacing targets, rendering vaccines obsolete. Some also acquire antibiotic resistance, creating dual threat.
Scientists now want a universal vaccine that targets all serotypes and blocks these undesirable outcomes. A British team took first step using reverse vaccinology - starting from genome, not germ. S. pneumoniae has over 2,000 genes, 1,300 common across 20,000+ isolates. They computationally screened for proteins that are surface-located, low similarity to human proteins, not attacking body tissue, and capable of robust durable immunity.
They shortlisted zinc metalloprotease B (Z), pneumococcal adherence factor A (P), and a YOP-like protein (Y). They made proteins Z, P, Y in lab, mixed them into experimental vaccine ZPY, added two boosters - synthetic CpG DNA and sugary chitosan - formulation ZPY-CpG-Ch.
Lab mice results were promising. ZPY-CpG-Ch elicited potent antibodies, protected 80-100% mice from lethal serotype 1, comparable to PCV13. Antibodies killed bacteria in test tube and protected unvaccinated mice when injected. It fully protected against lethal doses of non-vaccine serotypes 11A and 33F, and 50% against serotype 8.
Caveat: vaccinated mice still carried bacteria in upper respiratory tract and could spread infection to unvaccinated mice. Also tested on only 4 serotypes.
Still, this is baby step toward worthy goal - a universal pneumococcal vaccine that ends serotype replacement and antibiotic resistance trap.