Background

This Year, We Redefined Vaccine

In our world, billions of people are suffering from contagions. However, only a fraction of contagions can be prevented by the existing vaccines. The disadvantages of traditional vaccines, which are bothered to produced and purified and has strict requirements about temperature, limit their usage especially in developing countries.

the Comparison of Different Vaccine Delivery Ways

The key to the problems is to make a change in drug delivery methods 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 serious of fusion proteins(antigen, 2 kinds of adjuvants) which could penetrating the skin and work as traditional vaccine molecule. The fourth type of them 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.

The Way We Realize T-vaccine

1. Transdermal Peptide 1:

When this idea first stroke us, it seemed amazing that our dream is so naïve and unpractical. Above all, how can we make antigen get through the skin barrier? We refer to various transdermal methods, like Iontophoresis, Sonophoresis, Microneedles. They require special equipment and deal damage to 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 through intact skin. It creates a transient opening in the skin barrier to enable macromolecule 
to reach systemic circulation.

Phage Library Screening

With the use of eGFP, we could visualize whether the TD1-eGFP has transmited through 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.