Ospa

OspA (Outer Surface Protein A) is a major surface-expressed lipoprotein of the spirochete Borrelia burgdorferi, the causative agent of Lyme disease. The ospA gene encodes a 27 kDa protein that anchors to the bacterial outer membrane via a covalently attached lipid moiety at its N‑terminal cysteine residue. Structurally, OspA consists of a series of alpha‑helical segments that form a dimeric assembly, presenting antigenic loops accessible to host antibodies.

In the tick midgut, OspA expression is highly up‑regulated during larval feeding, facilitating bacterial adhesion to epithelial cells and preventing premature transmission to a mammalian host. When the tick molts and the spirochete is transferred to a vertebrate, ospA expression is sharply down‑regulated while other outer surface proteins such as OspC are induced, promoting colonization of host tissues. This phase‑variable regulation is controlled by a stringent response system and epigenetic mechanisms.

The immunogenicity of OspA has been exploited for vaccine development. One of the first licensed Lyme disease vaccines, LYMErix, consisted of recombinant OspA conjugated to a carrier protein and linked to alum adjuvant. The vaccine elicited high titers of anti‑OspA IgG, which could neutralize spirochetes in the tick midgut, thereby reducing transmission. However, concerns about autoimmune cross‑reactivity, low efficacy in high‑endemic areas, and declines in public acceptance led to its withdrawal in the United States. Novel subunit and adjuvant formulations are currently under investigation to improve safety and robustness of the immune response.

Detection of OspA or anti‑OspA antibodies is also employed in diagnostic assays to infer recent exposure to tick‑borne B. burgdorferi. In murine models, the presence of OspA mRNA in infected tissues correlates with early infection, whereas persistent expression has been noted during chronic phases in some hosts. Overall, OspA remains a key molecular marker for both the biology of Lyme disease transmission and the development of targeted interventions.