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Lyme Disease Test – The Promise of VOVO LIPS

lyme disease test heat map vovo lips antibody responses

VOVO proved to be the most effective indicator of Lyme disease infection in patients.

In 2010 the National Institutes of Health revealed that they had developed a more sensitive Lyme disease test, the VOVO LIPS test, than those currently available. This test could offer earlier detection of Lyme disease infection and was likely to have lower costs associated with it than the ELISA and Western Blot tests often criticised for lack of sensitivity and specificity in diagnosing Lyme disease. Two years later and it appears that the test is not yet in common use, so what happened to the promise of better Lyme disease testing?

VOVO LIPS Lyme Test Accuracy

The details of the studies on the VOVO LIPS test for Lyme disease were published in the journal Clinical and Vaccine Immunology. This luciferase immunoprecipitation system (LIPS) test appeared promising for detection not only of Lyme disease but a number of other infectious agents and fungal pathogens. Using the LIPS test in conjunction with the synthetic protein VOVO, the researchers reported diagnostic levels of 98-100% when analyzing the blood of healthy volunteers and patients with known Lyme disease infection.

New Lyme Test Better than ELISA

The current testing method recommended by the Centers for Disease Control (CDC) for Lyme disease involves a two-step process of an ELISA test followed by a Western Blot to confirm a positive ELISA where it occurs. Unfortunately, both tests have issues with sensitivity, particularly in early stages of infection, and both take considerable time at significant expense to carry out. Neither test is able to accurately discern an active or a prior infection and residual antibodies to the Lyme disease bacteria, Borrelia burgdorferi.

Lyme Disease Test for Europe and US

The VOVO LIPS test, therefore, looked set to become standard practice for Lyme disease diagnosis, offering an efficient, cost-effective, and accurate method of detection of infection. The inventors of the testing process also noted that it could be adapted for the various Borrelia strains active around the world, making the market for the test much larger than simply the US. The three researchers working on the invention were Peter D. Burbelo, Adriana Marques, and Michael J. Iadarola, working at the National Institute of Dental and Craniofacial Research (NIDCR) and the National Institute of Allergy and Infectious Diseases (NIAID).

LIPS Lyme Test to Monitor Treatment Effects

The researchers also noted the benefit of not having to perform the cumbersome dilutions and calculations required in Western Blot or ELISA testing as LIPS allows the technicians to genetically tag the antigens with luciferase and see if these antigens then bind to antibodies present in the patients’ samples. There is a considerable gap between positive and negative reactions in such testing, leaving it far less ambiguous and open to interpretation when deciding if a patient is positive or negative for Lyme disease (as can occur in other Lyme disease tests). The test may also be able to help monitor patients’ responses to treatment as it can detect changes in antibody titers over time with considerable accuracy; on other tests any drop may simply go unnoticed. Such testing could help identify patients with Chronic Lyme disease who have been misdiagnosed and remain untreated and may also go some way to explaining the differences in symptoms experienced by patients.

How VOVO LIPS Test Works


The current CDC-recommended two-tier testing for Lyme disease is so entrenched that labs have not taken up the VOVO LIPS test.

The VOVO LIPS test for Lyme disease is based on the fusion of protein antigens to a light-emitting enzyme reporter, Renilla luciferase (Ruc). These fused antigens are then able to be used in immunoprecipitation assays with serum samples and, afterwards, the level of light production is measured to give a highly sensitive titer for Lyme disease diagnosis. The synthetic protein antigen used in the test (VOVO) has been created by combining two alternating copies of immunoreactive peptides from the IR6 region of the bacterium and outer-surface protein C (OspC). Importantly, the synthetic recombinant protein used both Borrelia burgdorfer B31, the predominant US strain of Lyme disease bacteria, and B. garinii IP 90, common in Europe. Using this test the researchers found that there was more than a thousand-fold difference between the average antibody titer in those patients’ samples with Lyme disease and the controls. Such applications could also help in diagnosing Australian Lyme disease patients.

Why Is the Lyme Disease LIPS Test Unavailable?

In light of all of this positive news about the VOVO LIPS test for Lyme disease, why is it not replacing ELISA and Western Blot testing around the country and in Europe? The simple fact is that to adopt the new testing system the major laboratories running Lyme disease tests for physicians would have to incur considerable expense. Although this new test has been found to be better in terms of specificity and sensitivity than even C6 ELISA tests, the advantages do not appear to outweigh the time, effort, and money required to alter current practice. However, those labs that still use whole Borrelia ELISA tests are, perhaps, more likely to update their practice to include the newer tests as it is widely acknowledged that peptide-based assays give far more accurate results.

The Future of LIPS Lyme Tests

The researchers at the center of VOVO LIPS design are undertaking yet more studies to validate the diagnostic method, with a larger number of Lyme disease patients and development of a point-of-care LIPS application. More than twenty-five studies detailing LIPS findings have been published to date and interested Lyme disease doctors can access an online protocol and technical video of the LIPS assay via the Journal of Visualized Experiments. In the meantime, patients will simply have to wait for results of the ongoing validation studies before VOVO LIPS Lyme disease tests become commercially available.


PD Burbelo, et al. Rapid, Simple, Quantitative, and Highly Sensitive Antibody Detection for Lyme Disease. Clin Vaccine Immunol. 2010 Jun;17(6):904-9. Epub 2010 Apr 14.

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