To maintain stability and viability, most childhood vaccines must be kept cool – both heat and freezing can ruin them. That means they must be refrigerated at the correct temperature throughout transportation, storage, and delivery. This cold chain is difficult and costly to maintain, especially in developing countries. 
 
Dr. Sonenshein and his team are working to create childhood vaccines for diphtheria, tetanus, and pertussis (the DTP combination vaccine), and rotavirus-related diarrhea that can withstand a wide range of temperatures without refrigeration by encapsulating them in harmless bacterial spores that are naturally heat-resistant.  

The project team has created strains of B. subtilis that are engineered to express antigens for diphtheria, tetanus, pertussis, and rotavirus. Investigators have tested several of these strains in mice and have assessed these variables:

• Sites of antigen localization in B. subtilis, whether in the cell surface, spore surface, or cell cytoplasm.
  
• Route of inoculation, either oral or nasal.
  
• Need for adjuvant. 

Investigators are involved in ongoing experiments to answer two questions:

• To what extent does germination of spores contribute to an improved immune response?
• Is the ability to elicit a protective immune response stable in storage at temperatures common in the developing world?

Investigators also plan to test in monkeys the engineered strains of B. subtilis that have been effective in mice. In addition, they are collaborating with a Grand Challenges team led by Dr. David Lo to test whether the display of certain proteins on the surface of the spore can target these spores to M cells in the mucosal immune system.