This exam is due in class on March 14.  This project needs to be your own work.  I am looking for originality. You can consult me anytime. You may talk to classmates about your design, but I expect each student to present their own ideas. Use the concepts discussed in the papers presented in class plus any additional resources necessary. Don't forget to properly cite your work. When a lab procedure is discussed, briefly tell me the name of the procedure, the objective of the procedure and the results. This paper should be typed and written in an orderly way.

Your goal is to create a DNA vaccine against a virus of your choice. Research your virus to see what work has previously been done.  You need some immunological references regarding previous studies about the antigens that you’ll be displaying from your virus. Be sure to include an introduction to your virus and previous studies in your paper. Create your vaccine to get the maximum immunity possible (similar to specific immunity derived from normal exposure and recovery).  Decide what type or response you will need for maximum protection (humoral, cellular, or both).

Once you have made this determination, design your DNA vaccine to include the gene or genes that will maximize your protection.  Limit your viral gene choice to two genes. If desired, you can add two additional genes from other sources to stimulate a greater response. What plasmid will you place these genes into (keep in mind size restrictions)? Decide what modifications you need to add to your plasmid in order to get maximum transcription. Why did you choose the gene or genes you chose? How will you obtain your gene/genes?  How did you make enough copies for cloning? Where is/are the proteins naturally located in the mature virus particle? How will you obtain sufficient plasmid for vaccine use? Be sure to keep in mind your vector size and its limitation for gene insertion. What in-vitro test might you use to see if your genes are producing complete proteins that are correctly folded?

How will you deliver the DNA vaccine?  What is the target? What happens to the DNA once it enters the test subject?  What in vitro tests can be done to assure the plasmids are taken-up by the targeted cells? List the in vivo sequence of test subjects (assume there are appropriate animal models available) prior to human testing. How many doses and at what intervals will the vaccine be administered?  Why?

Assume you have successfully vaccinated a primate against your virus. How will you challenge your test subject? Did you have cellular proliferation? Do you have memory?  Did you produce neutralizing antibodies?  Did you add any cytokine? If so, did it increase or suppress your desired outcome?  What cytokine activation might have occurred after each vaccination of your test subject?  What effect did each of these cytokines have throughout the test period?  Do you expect long-term protection or do you recommend boosters?

If you were to do further research with this same virus, what are some of the different approaches you would try?