Spore Vaccine for Rotavirus

Heat-stable, injection-free vaccine platform

The invention is a novel vaccine platform utilizing the non-pathogenic bacterium Bacillus subtilis as the antigen-producer.  A desired antigen can be engineered to be under the control of a pro-vegetative state or a pro-sporulation promoter.  Cells are induced to express the desired antigen on the cell surface in the appropriate growth condition, and the cells are subsequently harvested and lyophilized.  The resultant vaccine is heat-stable at 45◦C for at least 17 months.

Features • Flexible production • Heat Stable • Safe

Applications • Vaccines for animal and human fields

Patent Status • US 9,610,333, Issued April 4, 2017 - Methods, compositions and kits for vegetative cell-based vaccines and spore-based vaccines

It is arguable that the impact of vaccines on human health is unequaled.  There is no other discovery that has led to the successful treatment of so many diseases, and has indeed eradicated two pathogens, namely smallpox and rinderpest virus.  Nearly all currently available vaccines require refrigeration, a factor that greatly limits their effectiveness in third world countries. For instance, rinderpest virus was the cause of a cattle disease endemic to Africa, causing widespread death of herds and resulting in regional famine.  A vaccine for rinderpest had been in existence since the 1960s, but attempted control of the disease was ineffective, largely due to poor vaccine stability and infrastructure.  However, in the early 1990s, a more heat-stable vaccine was created that allowed use of the vaccine in remote locations.  Within a decade, the rinderpest epidemic was under control and, in 2011, the United Nations declared the virus eradicated.  There are many diseases for which effective vaccines have been created but they are ineffective worldwide because of lack of stability in many environments.  Thus, there is a major need for a flexible platform that can be used to create diverse heat-stable vaccines.

A team at Tufts University has produced heat-stable vaccines, using tetanus and rotavirus as model targets, by engineering B. subtilis, a bacterium capable of entering into a vegetative or spore state.  Potential antigens were engineered to be expressed on the cell surface under the control of vegetative state or sporulation promoters.  The antigen-producing bacterial cultures were harvested and, after lyophilization, were stable for at least 17 months at 45◦C.  The lyophilized vaccines can be reconstituted in phosphate-buffered saline and delivered either by intranasal or sublingual routes to elicit a protective immune response.

Protective immunogenicity of lyophilized B. subtilis for tetanus (or control) after 17 month incubation at 45◦C dosed either via intranasal (IN) or sublingual (SL). 

Competitive Advantages
B. subtilis is a non-pathogenic bacterium found in a number of commonly ingested foods (e.g., rice), is amenable to engineering approaches to produce proteins of interest, and can be collected in the vegetative or spore states. The combination of safety, ease of production, and stability characteristics make this platform ideal for vaccine development, particularly for diseases affecting the developing world.

Tufts University Invention T001491

Licensing Contact

Emma Anderson