Maternal intranasal vaccination using novel Pneumolysin conjugated vaccines to protect offspring from pneumococcal infection

Summary

Streptococcus pneumoniae (pneumococcus) is a leading cause of bacterial pneumonia and sepsis in children, particularly in LMIC countries. The most effective public intervention to reduce pneumococcal diseases is vaccination. Despite the use of effective polysaccharide-based vaccines, pneumococcal disease still affects significant numbers of children worldwide. Underlying this continuing prevalence are increasing cases of disease caused by serotypes not protected by existing vaccines. 

As pneumococcus initially colonises the nasopharynx, local immunisation here via nasal spray is an appropriate and feasible vaccination strategy to control the nasal carriage which gives rise to subsequent invasive disease. New protein antigen based mucosal vaccines delivered to the nasal mucosa can provide strong protection and can protect against serotypes not currently protected by existing vaccines. 

Effectively vaccinating mothers can provide protection from birth and has been demonstrated to be effective against other streptococcal diseases (e.g. Group B Streptococcus). Moreover, mucosal vaccine delivery in mothers can also provide effective protection to offspring from bacterial infection.  

In this project, we will use preclinical models to demonstrate that mucosal maternal vaccination with novel pneumococcal vaccines can protect offspring from the establishment of pathogenic pneumococcal infections.

Project outcomes

Protecting offspring from susceptibility to infection by vaccinating their mothers can be an effective way to provide protection from infection from very early in life. This is due to the fact that mothers can transfer immune molecules to offspring while pregnant and while breastfeeding. If maternal vaccination can protect against Streptococcus pneumonia infection is unknown. Here we test how maternal vaccination against Streptococcus pneumonia can influence offspring immunity.

In this project we found that mothers vaccinated with two very different vaccines against pneumococcal bacterial infections transferred a striking immune effect to their offspring. Offspring acquired maternal antibody when very young, as expected. However, we found that offspring still had raised antibody levels against Streptococcus pneumonia when they had grown up. This suggests that offspring are acquiring a complex immune education from their mothers. This was supported by our detection CD4 T cells having a raised ability to launch anti-pneumococcal associated responses in offspring born to vaccinated mothers. Moreover, we also detected raised B cell populations in offspring born to vaccinated mothers. These cells maybe the source of long term anti- Streptococcus pneumonia antibody responses.

These findings therefore identify maternal vaccination as potentially a very effective way to induce long lasting immunity in offspring against Streptococcus pneumonia infections.