Background

2013, We Redefined Vaccine

In our world, billions of people are suffering from contagions while only parts of contagions can be effectively prevented by existing vaccines. The disadvantages of traditional vaccines, like being produced and purified with strict requirements on temperature, have limited their application, especially in developing countries.

the Comparison of Different Vaccine Delivery Ways

One solution to the problems is making change in drug delivery and create an in situ expression system based on synthetic biology.

Design of Project

This year, our project focused on a revolutionary vaccine delivery. We chose bacillus subtilis as chassis to establish a transdermal vaccine fresh secreting band-aid which consists of four engineering b.subtilis, each of them carries a gene circuit independently. By using an excellent transdermal peptide TD1, three of them could express a series of fusion proteins(antigen, 2 kinds of adjuvants), which could penetrate the skin and work as traditional vaccine molecules. The fourth type is our "reporter" , which could notify users whether the band-aid works well and when they could stick or tear off the patch. Moreover, we designed a reliable suicide system in Bacillus subtilis for the very first time in iGEM. Innovative and incredible, we plan to create a world without needles.

How do we realize T-vaccine

1. Transdermal Peptide 1:

When this idea first stroke us, it seemed that our dream is too naive and unpractical. The most obvious problem is to make antigen get across the skin barrier, and we looked up various transdermal methods, like Iontophoresis, Sonophoresis, Microneedles,all of which require special equipment and can harm skin. Our idea remained unrealistic until we find Transdermal peptide 1.

TD-1 is an eleven amino acid peptide, which can greatly facilitate macromolecule transdermal delivery through intact skin. This was first discovered by professor Wen Longping in our university and the results were published on Nature biotechnology.

TD1 Sequence
Title of Nature Letter About TD1

2. the Principle of TD1:

TD1 can greatly assist macromolecule transdermal delivery across intact skin. It creates a transient opening in the skin barrier, enabling macromolecule to reach systemic circulation.

Phage Library Screening

With eGFP, we could visualize whether the TD1-eGFP has transmitted across the skin. Besides, we can easily see the path of TD1-eGFP.

References

1.Chen, Y.P., et al., Transdermal protein delivery by a coadministered peptide identified via phage display. Nature biotechnology, 2006. 24(4): p. 455-460.
2.Scharton-Kersten, T., et al., Transcutaneous immunization with bacterial ADP-ribosylating exotoxins, subunits, and unrelated adjuvants. Infection and Immunity, 2000. 68(9): p. 5306-5313.
3.Glenn, G.M., et al., Transcutaneous immunization: A human vaccine delivery strategy using a patch. Nature Medicine, 2000. 6(12): p. 1403-1406.
4.Zhang, T., et al., Transmembrane Delivery and Biological Effect of Human Growth Hormone Via a Phage Displayed Peptide In Vivo and In Vitro. Journal of Pharmaceutical Sciences, 2010. 99(12): p. 4880-4891.
5.Prausnitz, M.R. and R. Langer, Transdermal drug delivery. Nature biotechnology, 2008. 26(11): p. 1261-1268.
6.van Dijl, J.M., et al., Functional genomic analysis of the Bacillus subtilis Tat pathway for protein secretion. Journal of Biotechnology, 2002. 98(2-3): p. 243-254.
7.Ogasawara, N., Systematic function analysis of Bacillus subtilis genes. Research in Microbiology, 2000. 151(2): p. 129-134.