Bacillus Spores as Vaccine Delivery Systems

Project Director
Tzipori, S.

Recipient Organization
TUFTS UNIVERSITY
200 WESTBORO ROAD
N. GRAFTON,MA 01536

Performing Department
Infectious Disease and Global Health

Non Technical Summary
The efficacy of vaccines diminishes when exposed to heat and desiccation. It is necessary to make oral vaccines available throughout the world by overcoming the problem of maintenance of the cold chain so that the vaccine will resist the environmental conditions and stay stable. The purpose of this research is to construct spore-forming bacterial strains that present vaccine antigens to the mammalian immune system in a way that will induce immunity to important childhood diseases (diphtheria-pertussis-tetanus and rotaviral diarrhea).

Animal Health Component

100%

Research Effort Categories

Basic

50%

Applied

25%

Developmental

25%

Classification

Knowledge Area (KA)	Subject of Investigation (SOI)	Field of Science (FOS)	Percent
722	3840	1090	100%

Knowledge Area
722 - Zoonotic Diseases and Parasites Affecting Humans;

Subject Of Investigation
3840 - Laboratory animals;

Field Of Science
1090 - Immunology;

Keywords

oral vaccine

oral immunization

childhood diseases

spore-forming bacterium

protective immune response

mice

macaque monkey;

Goals / Objectives
To make oral vaccines available throughout the world by overcoming the problem of maintenance of the cold chain by engineering the spore-forming bacterium Bacillus subtilis to be a vaccine delivery system that displays vaccine antigens for major childhood diseases (diphtheria-pertussis-tetanus and rotaviral diarrhea) on the surface of the spore or the vegetative cell. The advantages of using spores as the vaccine delivery system are 4-fold: (1) Bacterial spores are among the most resistant biological entities known with respect to extreme variations in temperature and hydration; (2) spores of Bacillus subtilis, the bacterium of choice, are known to be harmless when ingested; (3) industrial-scale production of spores is a well-characterized, inexpensive and safe method that can be easily applied in the developing world; (4) a spore-based vaccine can be used for oral immunization The goals of this research are: (a) To test rigorously the hypothesis that genetically engineered spores of B. subtilis can be used to vaccinate against major childhood diseases; (b) To compare the abilities of several B. subtilis surface proteins to display antigens in ways that induce a protective immune response; (c) To compare immune response induction by spores that display vaccine antigens directly on their surfaces and spores that need to germinate in the intestinal tract in order to express vaccine antigens on the surface of the vegetative cell.

Project Methods
Spores of each constructed strain will be fed to mice to assess safety and to measure the extent to which an appropriate immune response is induced. Promising candidate vaccine strains will then be tested in humans to assess safety. The major activities of this project are 1) the construction of strains of B. subtilis that display desired antigens on their cell surface, 2) testing these strains for their safety and effectiveness in inducing a protective immune response after ingestion by mice and macaque monkeys, and 3) assessing whether such spores are safe for human consumption and elicit appropriate immune responses.