THE TEN STEPS OF VACCINE DEVELOPMENT

BI160: Development of Vaccines teaches us to use a ten step paradigm to evaluate the process of vaccine development. In order to be effective, a vaccine must address each of these considerations. Here we present the progress of Lyme disease vaccine research in the context of these ten steps:

1. DEFINE DISEASE

Since 1976, the etiology of Lyme disease has been understood. The history of the classification of the disease is discussed in HISTORY and the effects of the disease are described under DIAGNOSIS.

2. DEFINE PATHOGEN

Since the discovery of the Lyme disease pathogen, Borrelia burgdorferi, in 1982, many elements of the pathogenesis have been elucidated. See ORGANISM and PATHOGENESIS for a complete explanation of these concepts.

3. OBSERVED IMMUNITY

Immunity to Borrelia burgdorferi is mediated primarily by the humoral immune system. The major isotypes observed in the response are IgM and IgG. See DIAGNOSIS.

4. CORRELATES OF IMMUNITY

Natural antibodies to Borrelia burgdorferi are poorly protective. No clear correlates of immunity in humans have been found. See EXISTING.

5. CRITICAL ANTIGENS

Critical antigens in the pathogenesis of Borrelia burgdorferi include OspA, OspC, p93, p39, p35, p37, p41, and many Erp proteins. For a discussion of these antigens see DEVELOPMENT, ORGANISM, and EXISTING.

6. ANIMAL MODEL

No perfect animal model has yet been found. Hamsters have been found to exhibit immune responses most similar to those of humans. Research is typically performed in hamsters, mice, dogs, and non-human primates. See EXISTING.

7. PRE-CLINICAL PROOF

LYMErix and another OspA based vaccine demonstrated protective immunity in animal models. See EXISTING.

8. FDA IND APPROVAL

LYMErix and another OspA based vaccine both received FDA approval in 1999. No other potential vaccines have yet received an IND. See EXISTING.

9. SAFETY/TOXICITY STUDIES

LYMErix and another OspA based vaccine both passed safety and toxicity trials, though only LYMErix received FDA approval. See EXISTING.

10. CLINICAL TRIALS

Only one vaccine has received FDA approval at this time. LYMErix was subsequently pulled from the market in 2002. No new products have reached widespread distribution. See EXISTING and HISTORY.