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State of Play in Lyme Disease Vaccine Research: Public Health Watch

OCT 23, 2019 | BRIAN P. DUNLEAVY
In general, it's a good news-bad news scenario for Lyme disease. 

The most recent estimates from the US Centers for Disease Control and Prevention (CDC) suggest that more than 300,000 Americans are diagnosed with the tick-borne disease annually, and that these numbers are increasing. Lyme disease is already the most common tick-borne illness in North America, and the CDC describes it as a “major US public health problem that causes substantial use of health care resources.” In addition, more than 100,000 cases are diagnosed in Europe each year.

Yet, even with these sobering statistics, there is no effective vaccine currently available to prevent Lyme disease in humans. Worse, efforts to develop a Lyme vaccine have been progressing in fits and starts over the past 2 decades, since GSK withdrew its LYMErix product from the market in 2002 due to declining sales amid reports of adverse reactions (not supported in subsequent analyses by the US Food and Drug Administration). Thankfully, though, the alleged weaknesses of the former vaccine has driven the field into new areas of research and allowed for development of new prevention strategies.
 
Indeed, experts in Lyme disease from industry, academia, and government gathered recently at the Cold Spring Harbor Laboratory Banbury Center to assess existing research and map out the “best pathways forward” in the development of an effective vaccine. Although the participants were quick to note that no votes were taken, nor consensuses reached, they generally agreed that “an effective vaccine is an important individual and public health tool to use in the United States and Europe.” Their discussions were summarized in an article published on October 17th in Clinical Infectious Diseases (CID), and effectively lay out the current state of vaccine research—both in terms of targets and progress.

“We felt that this is a topic that should be addressed,” said co-author Steven E. Schutzer, MD, professor, Department Medicine, Rutgers-New Jersey Medical School. “We decided to look at what is in front of us now or right on the horizon that can help solve this public health problem. We are aware that one can get Lyme disease more than once and I know a lot of people living in an endemic area want a vaccine.”

Ultimately, co-author Maria Gomes-Solecki, DVM, associate professor, Department of Microbiology, Immunology, and Biochemistry, University of Tennessee Health Science Center, said, “envision the development of hybrid vaccine strategies” designed to target both the offending microbe in Lyme disease— Borrelia burgdorferi—and its tick carrier.

As they note in CID, there are ongoing research efforts assessing the potential value of lipid immunogens, outer surface proteins, and live-mutant vaccines in inducing “protective immune responses” to B burgdorferi infection. For example, outer surface protein C (OspC) of B burgdorferi has been long considered as a vaccine candidate in Lyme disease because its synthesis is required by the bacteria for host colonization. Recent research suggests that antibody-mediated immunity to OspC can prevent dissemination of homologous B burgdorferi to the host during early infection, although such protection is “strain specific,” the authors note. At present, a dual vaccine antigen composed of OspC (epitope chimeric protein—chimeritope) and OspA has been approved by the US Department of Agriculture for use in dogs, while research assessing the viability of a human vaccine composed of several types of OspA remains ongoing.

Live-mutant vaccines are not likely to be approved for human use. However, the approach may help investigators identify “individual targets with protective efficacy to develop new recombinant vaccine candidates” as well as “reservoir-targeted or other animal vaccines,” the authors note.

Research into vaccines aimed at animal reservoirs, meanwhile, has to date focused primarily on platforms using purified recombinant OspA “as part of integrated pest-management interventions.”

Studies suggest that OspA-based vaccines are “effective against most species and strains of B burgdorferi,” while other outer surface proteins of B burgdorferi (BB0405, BBA52, BBI39) and tick antigens (subolesin, salivary proteins, tick salivary lectin pathway inhibitor, tick histamine release factor) are also being evaluated as potential transmission-blocking vaccine candidates.

Notably, according to the CID authors, the European Commission has funded the Anti-tick Vaccines to Prevent Tick-borne Diseases in Europe to “identify and characterize tick proteins involved in feeding and pathogen transmission,” with several “transmission-blocking and anti-tick vaccine candidates… currently undergoing efficacy studies in experimental animal models of tick-borne Lyme disease.” Similarly, in the United States, the National Institute of Allergy and Infectious Diseases (NIAID) earlier this year announced a “funding opportunity” called “Targeted Prevention for Tickborne Diseases” to encourage vaccine development.

In addition to describing new scientific approaches, the authors consider the societal implications of a new vaccine. “Lyme disease vaccination is an individual’s personal choice,” they note. “The concept of personal immunization against a non-contagious disease versus widespread vaccination to prevent the spread of a contagious infection should be part of public education and discussion.”

Future directions for Lyme disease vaccine research, the authors suggest, may include the generation of novel adjuvant molecules with potent immunostimulatory properties, the application of contemporary molecular and genetic approaches, and/or the advancement in nucleic acid–based vaccines (eg, DNA and RNA). These approaches, they write, “could be applied to newly defined antigens, or to previously defined immunogens that failed to provide sufficient efficacy or safety profiles.”

“We encourage all researchers to work on their ideas,” Schutzer told Contagion®. “We’re not advocating one approach over another, as we think all show promise in different ways. We’re hoping that this paper  stimulates discussion, both at research institutions and at the community level about potential solutions to the challenge of Lyme disease."
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