After walking through a forest or field of tall grass, public health agencies in many countries advise people to check their clothes, pets, and bodies for unwanted hitchhikers—ticks. These arthropods feed on the blood of mammals, such as mice, deer, livestock, and humans, as well as lizards and birds.1 Additionally, Ixodes ticks act as vectors, where they transfer disease-causing bacteria, viruses, or protozoa to their host during feeding.2
Scientists are particularly concerned about ticks transmitting bacteria from the Borrelia burgdorferi sensu lato complex–a group of spirochetes that includes the originally discovered species, B. burgdorferi. Researchers have determined that some of this complex’s genospecies cause Lyme disease in humans. During the disease’s early stages, patients often experience a bullseye-patterned skin rash emanating from the bite site, as well as fever, headache, and fatigue.3 Although clinicians treat diagnosed patients with antibiotics, undetected Lyme disease leads to more severe symptoms including meningitis, carditis, arthritis, and facial paralysis.3 Consequently, researchers are seeking approaches that prevent new infections. In a recently published Molecular Therapy paper, scientists produced an mRNA-based vaccine against Lyme disease.4
“It is the most common vector-borne disease in the United States,” said Matthew Pine, the lead author of this study and a former doctoral student in the laboratories of Norbert Pardi and Drew Weissman at the University of Pennsylvania. Because of climate change and habitat fragmentation, Lyme disease prevalence and distribution are rapidly increasing in North America and Europe.5 “When I started graduate school, the figure that I used was there are about 300,000 cases every year [in the United States]. But four years into my research, the standard number had changed to almost 500,000.”
Pine and his colleagues, including Weissman who along with Katalin Karikó was awarded the 2023 Nobel Prize in Physiology or Medicine for their work on mRNA vaccines, developed a lipid nanoparticle (LNP)-encapsulated, nucleoside-modified mRNA vaccine that encodes the outer surface protein A (OspA) from B. burgdorferi. OspA is widely conserved among the bacteria in the B. burgdorferi sensu lato complex, which makes it a great target. But this was not the first prophylactic vaccine targeting OspA. In 1998, the Food and Drug Administration (FDA) approved an OspA-based recombinant protein vaccine for human use, called LYMErix, produced by GlaxoSmithKline (GSK).6 However, some researchers became concerned that the vaccine could cause arthritis. Although scientists could not find evidence supporting these claims, the efficacious vaccine was voluntarily removed from the market by GSK. Currently, a new recombinant OspA protein vaccine is going through phase III clinical trials, but as of right now, there are no prophylactic vaccines approved by the FDA to prevent Lyme disease in humans.
The researchers first tested how their OspA mRNA vaccine affected cells of the adaptive immune system by isolating immune cells from mice immunized with OspA mRNA, OspA protein, or control mRNA, and quantifying them using flow cytometry. Compared to the OspA protein and control vaccines, their OspA mRNA vaccine induced a greater proportion of memory B cells in the spleen, where these cells enhance the adaptive immune response after antigen re-exposure. Moreover, mice vaccinated with OspA mRNA had an increased abundance of antibody-producing, long-lived plasma cells within their bone marrow in contrast to mice immunized with control mRNA, but not those immunized with OspA protein.
To see if these differences in immune cell frequency affected antibody production, the researchers collected serum samples from mice vaccinated and boosted with one of the three vaccines. Through enzyme-linked immunosorbent assays, they determined that OspA mRNA augmented the anti-OspA IgG titer compared to the other vaccines. This suggested that their mRNA vaccine produced greater immunogenicity than a protein-based vaccine.
Additionally, Pine and his colleagues examined the protective efficacies of the three vaccines against infection by immunizing the mice and challenging them with B. burgdorferi. Using quantitative PCR to detect the bacteria, the researchers found that 80 percent of mice vaccinated with OspA mRNA were protected from B. burgdorferi infection compared to 50 percent and 0 percent with the OspA protein and control mRNA, respectively. This indicated that their OspA mRNA vaccine also had greater efficacy than an OspA protein vaccine and suggested that clinicians could develop an mRNA-based vaccine to prevent Lyme disease in humans.
See Also “Nobel Prize for mRNA Vaccines”
I think [this study] just further demonstrates the power of mRNA and the potential that it holds.
-Matthew Pine, University of Pennsylvania
“I think that for Lyme disease vaccines, the more options, the better,” said Maria Gomes-Solecki, a microbiologist and immunologist from the University of Tennessee Health Science Center, who was not involved in the study. Her team recently developed an intranasal, viral vector-delivered vaccine based on OspA and summarized their results in a preprint posted on Research Square.7 However, she wonders if the authors’ results would be the same if they examined the immunogenicity and efficacy of the mRNA and protein vaccines at later time points. “Within the six-month period that they have done in this paper … I do not think that there is going to be many differences between these two [vaccines],” Gomes-Solecki stated. “Now, if you do a long term study, past one year, … then you may start seeing [more] differences between the delivery methods.”
Pine attributes his success in this project to the researchers who advised him along the way. “It was just really helpful to have that mentorship from other scientists who were experts in their field and to take me under their wing and help me grow as a scientist,” Pine recalled. After finishing his graduate degree, he is now working as a scientist at InVitro Cell Research, where he is investigating RNA therapeutics, including those based on mRNA. “I think [this study] just further demonstrates the power of mRNA and the potential that it holds.”
- Eisen L, Eisen RJ. Changes in the geographic distribution of the blacklegged tick, Ixodes scapularis, in the United States. Ticks Tick-Borne Dis. 2023;14(6):102233.
- Narasimhan S, et al. A ticking time bomb hidden in plain sight. Sci Transl Med. 2023;15(718):eadi7829.
- Murray TS, Shapiro ED. Lyme disease. Clin Lab Med. 2010;30(1):311-328.
- Pine M, et al. Development of an mRNA-lipid nanoparticle vaccine against Lyme disease. Mol Ther. 2023;31(9):2702-2714.
- Goren A, et al. Demographic patterns in Lyme borreliosis seasonality over 25 years. Zoonoses Public Health. 2023;70(7):647-655.
- Dattwyler RJ, Gomes-Solecki M. The year that shaped the outcome of the OspA vaccine for human Lyme disease. Npj Vaccines. 2022;7(1):1-5.
- Gingerich MC, et al. A parainfluenza virus 5 (PIV5)-vectored intranasal vaccine for Lyme disease provides long-lasting protection against tick transmitted Borrelia burgdorferi in mice. Preprint. Res Sq. 2023:rs.3.rs-3143132.