Using deliberate infection to study deadly diseases
Infectious diseases like meningitis and whooping cough cause severe – often fatal – illness. We are one of very few centres worldwide able to safely infect healthy volunteers to study them.
We’ve used this to find new ways of preventing infection and advance vaccination efforts.
We are one of very few centres worldwide able to safely infect healthy volunteers to study fatal disease like meningitis and whooping cough.
This has allowed us to study how people ‘carry’ the bacteria which cause these diseases in their nose, and develop pioneering new nose drops to treat them.
Curbing ‘silent’ infections
It’s normal for disease-causing bacteria to spread between our noses and throats without any symptoms. Some vaccines work by curbing this silent infection and spread (inducing herd immunity).
Our 2014 study of new vaccines showed this effect on Neisseria meningitidis bacteria, which causes meningitis. The Joint Committee for Vaccination and Immunisation (JCVI) used this as evidence to deploy these vaccines for herd immunity.
Developing nose drops against meningitis
Herd immunity can occur naturally. N.meningitidis is commonly displaced in infants by its harmless cousin Neisseria lactamica.
We pioneered controlled infection of adults with N.lactamica, and found it reduced the amount of N.meningitidis in their nose and throat. We went on to show it also boosted the immune system, so they were better prepared against future infection.
We analysed changes N.meningitidis’ DNA over the course of 6 months inside the nose (published here). That gave insights into its adaptations and evasion of the immune system. It also opened our eyes to the potential of N.lactamica nasal drops in preventing outbreaks.
We inserted a gene from N.meningitidis into N.lactamica to make them more `sticky’ to nose cells, and resemble N.meningitidis.
In a world-first controlled infection with genetically modified bacteria, we showed stronger resulting immunity against N.meningitidis (published here).
We’re now refining this, and trialling freeze-dried N.lactamica in Africa, where major outbreaks occur.
Fighting whooping cough
We have also applied this to whooping cough. Caused by Bordetella pertussis bacteria, sporadic outbreaks drive severe – sometimes fatal – breathing distress. It hits infants especially hard.
Scientists came up with a theory that outbreaks stem from silent nasal carriage of B.pertussis. Our controlled infection studies were key to confirming this and advancing prevention.
We proved adults carry B.pertussis without symptoms. We also detailed immune and antibiotic effects, and the value of different tests (published here).
We are now developing new infection measures, enabling vaccine trials for herd immunity.
Our future work will engineer N.lactamica to fight more diseases, like COVID-19 and influenza. This ground-breaking approach promises to reduce their impact on our communities.