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mRNA Enters the New Frontier: A Tick-Borne Bacteria-Targeting mRNA Vaccine to Prevent Lyme Disease

Lyme disease, a natural epidemic caused by Borrelia burgdorferi infection, is usually transmitted to humans by the bite of a blacklegged tick and can cause fever, headache, fatigue, and rash. If left untreated, the infection can spread to the joints, heart, and nervous system.

Most people with Lyme disease can be successfully treated with a few weeks of antibiotics, but some will develop Post-Treatment Lyme Disease Syndrome (PTLDS), which can lead to long-term symptoms such as severe joint pain and neurocognitive problems. There is currently no Lyme disease vaccine approved for routine human use.

The COVID-19 pandemic has led to the rapid approval and mass adoption of the mRNA COVID-19 vaccine. As a result, some researchers have begun to study the preventive potential of mRNA vaccines in the prevention of tick-borne diseases.

Recently, Norbert Pardi's team at the University of Pennsylvania, in collaboration with mRNA vaccine pioneer Prof. Drew Weissman, published a research paper entitled Development of an mRNA-lipid nanoparticle vaccine against Lyme disease in Molecular Therapy.

The study used a lipid nanoparticle-encapsulated modified mRNA (mRNA-LNP) platform to create a vaccine against Lyme disease. LNP was used to deliver mRNA for OspA, which is an antigen produced by Borrelia burgdorferi, the pathogen that causes Lyme disease. Mice that were given a single dose of the OspA mRNA-LNP vaccine had positive humoral and cellular immune responses.

These robust immune responses led to protection against Burkholderia sp. infection, and this study suggests that highly effective mRNA vaccines can be developed against bacteria in addition to viruses.

Back in November 2021, Erol Fikrig's team at Yale University School of Medicine joined forces with mRNA vaccine pioneer Professor Drew Weissman to publish a cover paper in Science Translational Medicine.

The study created an mRNA vaccine against blacklegged ticks that uses lipid nanoparticles (LNPs) to deliver mRNAs for 19 proteins (19ISPs) found in blacklegged tick saliva. These proteins cause a rapid skin response to tick bites, which limits the time it takes for the ticks to feed on the host's blood and infect them and also lets the host quickly detect the tick bite, stopping the ticks from spreading Lyme disease.

It is worth noting that the mRNA vaccine developed in this study is targeted at the black-legged tick, not the specific pathogen transmitted by the black-legged tick. Tick bites are often not felt by us because the ticks secrete substances that anesthetize the skin. The mRNA vaccine developed in this study would allow the immune system to recognize the tick and prevent infection with Lyme disease. Moreover, the vaccine would make the tick bite quickly red and itchy, making tick bites as quickly detected as mosquito bites, thus further helping to remove the pathogen before it is transmitted.

In this latest study, published in Molecular Therapy, Norbert Pardi's team at the University of Pennsylvania, in collaboration with Professors Drew Weissman and Erol Fikrig, developed an mRNA vaccine that directly targets Burkholderia cepacia, the causative agent of Lyme disease.

B. burgdorferi are more complex bacteria than viruses, making it more challenging to develop effective vaccines against them. Norbert Pardi's team identified a protein in B. burgdorferi, outer surface protein A (OspA), that elicits an effective immune response and is an ideal target for preventing B. burgdorferi infection and the development of Lyme disease.

The team used the mRNA-LNP vaccine technology, which was proven to work in the COVID-19 vaccine, to wrap and send mRNA that expresses OspA using LNP. Preclinical animal model experiments demonstrated that the mRNA-LNP vaccine, which targets OspA, induced a strong antigen-specific antibody and T-cell response after a single dose, thereby preventing Burkholderia sp. infection. More importantly, the vaccine elicited a strong memory B-cell response that can be activated long afterward to help prevent subsequent Burkholderia sp. infections.

The experimental mRNA vaccine developed in this study provided effective protection against Burkholderia sp. infection in a preclinical animal model, the team said. This study suggests that mRNA vaccines can prevent Lyme disease and may be a powerful tool to reduce the number of Lyme disease cases and post-treatment Lyme disease syndrome (PTLDS).