Lyme disease, caused by the pathogenic spirochete Borrelia burgdorferi (Bb) is a major public health problem which warrants further efforts towards the development of improved vaccines and new diagnostics. The investigators have discovered a new family of lipoproteins (termed """"""""2.9"""""""" lipoproteins) that appear to be """"""""differentially expressed"""""""" by Bb; i.e., some of these lipoproteins are expressed as Bb replicates in vitro (analogous to the arthropod phase of Bb's life cycle) whereas others are expressed as Bb replicates """"""""in vivo"""""""" (i.e., during the mammalian phase of infection). Compelling preliminary data already support the expectation that those 2.9 lipoproteins expressed """"""""in vivo"""""""" may serve as effective vaccines and serodiagnostic reagents.
The Specific Aims of this proposal are: (1) To determine and compare the """"""""in vitro"""""""" versus """"""""in vivo"""""""" expression patterns for the 2.9 lipoproteins of Bb strain 297; (2) To assess whether the 2.9 lipoproteins (particularly those express by Bb under """"""""in vivo"""""""" conditions) are surface-exposed in Bb and thus targets for protective antibodies (i.e., vaccine candidates); (3) To investigate the 2.9 lipoproteins as new antigens for the serodiagnosis of Lyme disease; and (4) To examine the presence of homologous 2.9 lipoproteins (particularly those with vaccinogenic and diagnostic importance ) in all three sensu lato genospecies of B. burgdorferi. A particularly novel aspect of this proposal is its reliance upon a new animal model system in which virulent, """"""""mammalian host-adapted"""""""" Bb can be obtained from rat or rabbit peritoneal chambers in quantities sufficient to identify 2.9 lipoproteins of Bb expressed """"""""in vivo."""""""" The power of utilizing these new animal model systems for sorting out the """"""""in vitro"""""""" versus """"""""in vivo"""""""" expression patterns for 2.9 lipoproteins lies in the fact that antigens expressed during each or both phases of the zoonotic life cycle of Bb can be selectively chosen to address contemporary issues in Lyme disease vaccine development and serodiagnosis.
