2. Lyme Disease and The Lyme Disease Vaccine Presentation By Jason Hadrath

3. What is Lyme Disease?  A multisystem inflammatory disease.  Characterized by inflammation of: 1. connective tissue (skin and joints) 2. nervous tissue 3. cardiac tissue  Resulting from an infection of Borrelia burgdorferi  Transmitted by Ixodes ticks

4. Symptoms and Stages  Early  Erythema migrans and flu-like symptoms. BEST POINT FOR TREATMENT !! 40 % of lyme cases are asymptomatic in the early stages.  Middle  Arthritis-like joint pain, heart arrhythmia, and fatigue.  Late  Chronic arthritis, memory loss, and dementia.

5.  100 years of lyme disease.  First classified in 1975 by Dr. Allen Steere.  Named after Old Lyme Connecticut. You are here. New Britain Old Lyme Connecticut History

6.  Lyme disease is the most common tick-transmitted illness in North America.  From 1980 to 1998 112,000 cases have been reported.  The true number of cases may be significantly higher.  Lyme disease costs about $1 billion per year. Statistics

7.  Ixodes scapularus (dammini )  Ixodes americanum  Ixodes pacificus  Ixodes riciaus  Ixodes persulcatus The Tick

8. More Ticks Ixodes americanum Ixodes scapularus Larvae Ixodes pacificus

9. Life Cycle Year 1  Early Spring  Female drops off deer and lays eggs on the ground.  Spring / Summer  Larvae hatch and attach to white- footed mice.  Late Summer / Fall / Winter  Larvae molt to nymphs which over winter in the soil without feeding.

10. Life Cycle Year 2  Spring / Summer  Nymphs emerge and attach to mice, deer, and people.  Fall  Nymphs molt to adults and attach to mice, deer, and people.  Late Fall / Winter  Adult ticks on deer making and carrying eggs.

12. Borrelia burgdorferi  Discovered by Willy Burgdorfer in 1984.  Gram negative spirochete bacteria.  Entire genome is 1 MB. Consisting of 1 linear chromosome and 19 circular plasmids

13. Borrelia burgdorferi cont..  One of the plasmids is most likely to code for virulence.  Is found in the mid gut of the tick.  Has an unusually large variety of surface proteins, which are both itís strengths and weaknesses.

14. Outer Surface Protein A  Lipoprotein.  Single polypeptide chain of 257 amino acids.  Lipid is covalently bonded to the N terminus.

15. Interactive Chain HChain L

16. The Vaccine  LYMErix.  Developed by SmithKline Beecham Biologicals.  Noninfectious vaccine.  Given in three doses. Two doses, one month apart and again in 12 months.  Consisting of the complete lipoprotein OspA and aluminum hydroxide (adjuvant).  Cost $ 85 00 per shot.

17. The Vaccine cont...  Expressed in E. coli strain AR58.  Transformed with plasmid pOA15.  With OspA (a plasmid gene) as its insert.  The lipid moiety was added post- translationaly

18. Mechanism of Action  An injection of OspA results in the formation of anti-OspA antibodies.  These antibodies possess bactericidal activity.  Antibodies taken in along with tickís bloodmeal.  B. burgdorferi destruction ensues. Here is the key !

19. Vaccine Efficacy  10,000 person study.  49% effective after two doses.  76% effective after all three doses.  After three doses 100% effective in preventing asymptomatic infection.

20. Reservations  Lack of long term testing.  Is a booster dose needed?  OspA contains a sequence that is similar to the human protein LFA-1.  This could lead to an autoimmune disease.

21. References Books Biddle, W. Afield Guide to Germs. New Jeresy: Doubleday Publishing Groupe,1995. Ginsberg, H.S. Ecology and Environmental Management of Lyme Disease. New Jersey: Rutgers University Press, 1993. Lang, D. Coping with Lyme Disease. New York: Henery Holt and Company, 1993. Silverstein, A. Lyme Disease the Great Imitator. New Jersey: Avstar Publishing Corp., 1990. Journals ìImmunization Against Lyme Disease - An Important First Step.î The New England Journal of Medicine July 23,1998: 263-264. Marwick, C. ìGuarded Endorsement for Lyme Disease Vaccine.î JAMA June 24, 1998: 1937-1938. Sigal, L.H. ìA vaccine consisting of Recombinant Bb OspA to Prevent Lyme disease.î The New England Journal of Medicine July 23,1998: 216-221.

22. References Journals Steere, A.C. ìVaccination Against LD with Recombinant Bb OspA with Adjuvant.î The New England Journal of Medicine July 23, 1998: 209-214. Telford S.R. ìEfficancy of LD Vaccine Formulations in a Mouse Model.î The Journal of Infectious Diseases May, 1995: 1368- 1370. Sanz C. ìSummer of Danger.î Discover May, 1999: 64-71. Web sites http://www.lymerix.com SmithKline Beecham Bio. http://www.aldf.com American Lyme Disease Foundation, Inc. http://www.uri.edu/ticklab The Tick Research Lab. hppt://www.ent.iastate.edu/imagega Iowa State Entomolgy Image Gallery.

23. References Web sites http:www.acponline.org/lyme American Academy of Physicians http://www.cdc.gov/ncidod/dvbid/lymeinfo.htm Centers for Disease Control and Prevention. http://thetick.powertie.org Brandons Tribute to the Tick.

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