Yale researchers develop mRNA-based lyme disease vaccine

Yale researchers have developed an mRNA vaccine that targets the antigens found in tick saliva in order to alert individuals to tick bites as well as prevent the tick from feeding correctly, thereby reducing its ability to transmit pathogens.

Yale researchers have developed an mRNA vaccine against lyme disease that triggers an immune response at the site of a tick bite and provides partial protection against the disease-causing bacteria.

In a paper published on Nov. 17 in the Science Translational Medicine journal, scientists studied specific ticks called “Ixodes scapulari” that carry a lyme-disease-causing bacteria called “Borrelia burgdorferi.” According to Gunjan Arora, one of the co-first authors of the paper and an associate research scientist at the Yale School of Medicine, lyme disease is the fastest-growing vector-borne illness in the United States, with close to half a million people affected every year. Currently, there are no commercially available vaccines for lyme disease. This novel vaccine is unique in that it targets the vector of transmission, the tick, rather than the actual pathogen itself.

“Lyme disease is the most common Tick–borne human illness in the United States, leaving an urgent need for either therapies or preventative strategies, such as a vaccine,” Jacqueline Mathias dos Santos, a co-first author on the paper and a postdoctoral associate at the School of Medicine, wrote in an email to the News. “Our vaccine is unique in that we don’t actually target the pathogen, we target the vector … instead. This strategy can work for Borrelia because it takes around 24 hours of tick feeding for the pathogen to be transmitted. This offers a unique opportunity to disrupt transmission. Additionally, by targeting the vector, we don’t expect this to drive resistance by the pathogen.”

Traditionally, vaccines are developed to target specific viruses or bacteria that can cause disease. However, this new lyme disease vaccine is designed to target tick salivary proteins, according to Matias dos Santos.

According to Matias dos Santos, when the tick bites an animal, it releases salivary proteins through the open wound. The mRNA vaccines are designed so that the immune system recognizes these proteins, sees them as an antigen and triggers a strong immune response at the site of the bite.

“Ticks don’t feed well on vaccinated animals and fall off quickly,” Arora wrote. “The animals develop redness within 24 hours where the tick is feeding. This will give the opportunity for hosts to remove ticks before the pathogen is transmitted. The vaccine also provides partial protection from Lyme disease to the subject even if ticks are not removed.”

Ticks can be difficult to detect due to their small size. By eliciting an immune response at the site of the bite, hosts can more easily and quickly identify the bite and remove the tick before it has a chance to transmit the pathogen. Ticks need to stay attached for 24 hours in order to transmit the bacteria, according to Matias dos Santos. According to Matias dos Santos, their preliminary findings in vaccinated guinea pigs during the study showed that none of the animals that were bitten by infected ticks tested positive for the bacteria.

“[Vaccinated] Guinea pigs … developed erythema at the site of tick attachment, a feature of acquired tick resistance,” the paper states.

According to both Arora and Matias dos Santos, the technology behind this vaccine has been decades in the making. They both credited the project as a group effort led by Erol Fikrig’s laboratory at the Yale School of Medicine and Drew Weissman’s laboratory at the Perelman School of Medicine at the University of Pennsylvania.

Both researchers said that their vaccine, similarly to the COVID-19 mRNA vaccines, uses mRNA encapsulated in lipid nanoparticles. However, unlike the COVID-19 vaccines that target a single antigen — the spike protein on SARS-CoV-2 — the lyme disease vaccine targets 19 antigens — the different salivary proteins in tick bites.

“One of the differences that we can mention between the vaccines is that COVID-19 encodes a single viral glycoprotein called spike (S) of SARS-CoV-2, whereas our vaccine encod[es] 19 salivary proteins from I. scapularis,” Matias dos Santos wrote. “ It is noteworthy that tick saliva is a complex blend of several proteins that are dynamically expressed depending on tick feeding and resulting changes in host responses. We used 19 salivary proteins that have a spectrum of functions in tick feeding, interaction with the pathogen, or host responses, reflecting a portion of what is expressed in [a tick’s] salivary gland.”

The vaccine has been tested on guinea pigs but has not yet undergone clinical trials, according to Arora. Fikrig explained that the vaccine will need to undergo human trials in order to determine whether it is effective in humans.

Ticks are classified as arachnids and are closely related to spiders and scorpions.