Ticking Multiple Boxes
Preclinical data for a new multivalent Lyme disease vaccine looks promising
Michael Schubert |
Lyme borreliosis is the most common vector-borne infection in the northern hemisphere – and it is rapidly becoming more prevalent. Recent studies reported 300,000 Lyme disease cases in the US (1) and over 65,000 in Europe (2), despite known underreporting. And though a vaccine was developed for use in humans, it was voluntarily withdrawn from the market because of poor performance (3). There is currently no vaccine available for protection against Borrelia – the causative bacteria.
Previous generations of Lyme borreliosis vaccines have shown that the disease can be prevented by immune targeting of outer surface protein A (OspA), a dominant antigen of the Borrelia spirochete. When present in the gut of a tick, the spirochete abundantly expresses the OspA lipoprotein, which appears to act as an antibody shield for the tick while it feeds. Studies have already shown that antibodies targeting the C terminal domain of OspA are crucial for protection against Lyme borreliosis. Vaccines based only on that portion of the protein confer partial protection.
To address the ongoing need for Lyme borreliosis prevention, a research group from Valneva SE recently designed a multivalent vaccine based on the OspA protein (4). Because there are four Borrelia species in Europe expressing a total of six different OspA serotypes, the vaccine contains three separate proteins, each of which contains the C terminal halves of two OspA serotypes linked to form heterodimers. The researchers also introduced disulfide bonds to stabilize the protein fragments and a lipidation signal to increase immunogenicity.
The vaccine was tested in mice challenged with either infected ticks or in vitro grown spirochetes. Four to six weeks later, the researchers tested their blood using an ELISA assay against Borrelia garinii and extracted DNA from ear or urinary bladder tissue to attempt PCR or qPCR detection of spirochete DNA. In all cases, the vaccine introduced a significant degree of protection. Renowned vaccinologist Stanley A. Plotkin said, “These preclinical data are an encouraging step towards a vaccine that is badly needed” – and if the new vaccine performs as well in clinical trials as it has to date, the future of Lyme disease prevention looks promising.
- Centers for Disease Control and Prevention, “How many people get Lyme disease?”, (2013). Available at: 1.usa.gov/1s0Y9If. Accessed January 13, 2015.
- A Rizzoli et al., “Lyme borreliosis in Europe”, Euro Surveill, 16, 19906 (2011). PMID: 21794218.
- LE Nigrovic, KM Thompson, “The Lyme vaccine: a cautionary tale”, Epidemiol Infect, 135, 1–8 (2007). PMID: PMC2870557.
- P Comstedt et al., “Design and development of a novel vaccine for protection against Lyme borreliosis”, PLoS One, 9, e113294 (2014). PMID: PMC4237411.