DEVELOPMENT OF A NOVEL LYME VACCINE

A collaborative effort between Lyme MCW and Lochhead Scientific

Lochhead Scientific (LS) has recently synthesized a two-component conjugate vaccine candidate that combines OspA with a highly immunogenic T cell antigen that was identified through research conducted at the Medical College of Wisconsin (MCW) (Danner et al., 2024). This immunodominant T cell antigen is derived from the broadly conserved methyl-accepting transducer domain (MATD) from the Bb chemotaxis protein Mcp4. LS’s vaccine candidate consists of the Mcp4 MATD as the T-cell immunogen linked to OspA as the B-cell immunogen (patent pending). 

Significance

There is an urgent and unmet need for a safe and effective Lyme disease (LD) vaccine (Plotkin, 2016). The LD pandemic is expanding unabated, with an estimated global seroprevalence of Borrelia burgdorferi (Bb) infection of 14.5% (Dong et al., 2022). In the U.S., there are nearly 500,000 cases of LD annually (Kugeler et al., 2021). LD-related health care costs in the U.S. are as high as $1.3 billion each year (Adrion et al., 2015). Current vaccine candidates in development block transmission of Bb by targeting the outer surface protein A (OspA) as the B cell immunogen (Wormser, 2022) Although safe and modestly effective, OspA-based vaccines only provide short-term protection and require frequent boosts (Steere, 1998) (Schoen et al., 2003). Lochhead Scientific’s novel two-component conjugate vaccine candidate incorporates both T cell and B cell immunogens to boost long-term efficacy by generating high-affinity, long-lasting antibody responses to OspA.

Previous & Current Lyme Vaccine Candidates

LYMErix™, developed by GSK and FDA-approved in 1998, was safe and moderately effective (Steere et al., 1998). However, a two-dose series provided only ~50% protection, and a three-dose series provided ~75% protection in humans and mice. This vaccine was removed from the market shortly after FDA approval in 2002 due to lack of demand, the need for frequent boosters, weak recommendations by the CDC, and pending lawsuits by Lyme disease activists who believed that the OspA vaccine caused significant adverse reactions, these claims of which were later proven false

VLA15, developed by Valneva/Pfizeris a hexavalent OspA-based vaccine candidate that incorporates North American and European Lyme OspA serotypes, requires a 3-shot regimen and annual boosters to maintain efficacy. OspA is rapidly downregulated during tick-to-human transmission, and OspA and other surface lipoproteins used as vaccine targets are expressed on highly genetically variable plasmids. Furthermore, OspA is a weak T cell antigen and only a subset of infected patients develop T cell responses to OspA. Together, these data indicate that vaccines targeting OspA alone may be sub-optimal.

Methyl-Accepting Chemotaxis Proteins (Mcps) are highly important in Borrelia chemotaxis and motility. Located at the poles of Borrelia in trimers of dimers, Mcps bind chemoeffectors, such as sugars or tick salivary proteins, and drive chemotaxis through signaling proteins which themselves drive chemotaxis by signaling to the flagellar motor. They show high conservation between North American and European Lyme disease spirochetes, and are essential for immune invasion.