Lyme Disease and

The Lyme Disease Vaccine

Presentation By

Jason Hadrath

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

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.

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

ConnecticuConnecticutt

History

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

Ixodes scapularus (dammini )

Ixodes americanum

Ixodes pacificus

Ixodes riciaus Ixodes persulcatus

The Tick

More Ticks Ixodes americanum

Ixodes scapularusLarvae

Ixodes pacificus

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.

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.

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

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.

Outer Surface Protein A

Lipoprotein.

Single polypeptide chain of 257 amino acids.

Lipid is covalently bonded to the N terminus.

Interactive

Chain HChain L

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 $ 8500 per shot.

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

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 !

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.

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.

References BooksBiddle, 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.

ReferencesJournalsSteere, 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 siteshttp://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.

References

Web siteshttp: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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Any questions ?