This mRNA vaccine successfully prevented the development of Lyme disease in guinea pigs after tick bite and removal.
Caused by the bacterium B. burgdorferi and more rarely, B. mayonii, Lyme disease is transmitted through the bite of infected black-legged ticks and is known to cause fatigue, fever, joint pain, and skin rashes, among other serious joint and nervous system complications.
In the United States, Lyme is considered to be the most common vector-borne disease, affecting around 30,000 people annually. In 2019, nearly 40,000 cases of Lyme disease were reported to the Centers for Disease Control and Prevention. However, the number of actual illnesses is likely to be greater than what is reported as recent studies have estimated that there are about 476,000 new annual cases of Lyme in the US. Given its widespread prevalence, scientists have sought to design a vaccine to minimise infections.
Leveraging the mRNA technology that has been proven to be effective against SARS-CoV-2, researchers at Yale University, in collaboration with a team led by Drew Weissman at the University of Pennsylvania, have recently designed a novel vaccine for Lyme disease. The vaccine reportedly offers protection against the bacterium when tested in guinea pigs and can potentially be applied to combat other tick-borne diseases. Unlike traditional approaches that focus on triggering an immune response against a pathogen, this latest innovation works by initiating a quick response in the skin to components of tick saliva to limit the amount of time that ticks have to feed upon and infect the host.
“There are multiple tick-borne diseases, and this approach potentially offers more broad-based protection than a vaccine that targets a specific pathogen,” said senior author Erol Fikrig, the Waldemar Von Zedtwitz Professor of Medicine (infectious diseases) at Yale and professor of epidemiology (microbial diseases) and microbial pathogenesis. “It could also be used in conjunction with more traditional, pathogen-based vaccines to increase their efficacy.”
The saliva of black-legged tick I. scapularis, which transmits B. burgdorferi, is composed of many proteins. In the study, the team analysed bits of mRNA that is responsible for producing 19 different saliva proteins to develop the vaccine. The scientists then tested the vaccine on guinea pigs, which have been used as a model to study Lyme disease and tick resistance.
Their findings showed that the vaccinated group that was exposed to infected ticks quickly developed redness at the bite site. However, as long as the ticks were removed when redness appeared, none of the immunised subjects contracted Lyme disease. In contrast, around half of the non-immunised guinea pigs were infected with B. burgdorferi even after the ticks were removed.
To test the extent of their vaccine’s protective effect, the scientists attached a single infected tick to the guinea pigs and did not remove it. It was observed that none of the immunised guinea pigs was infected whilst 60 per cent of the non-immunised group became infected. Furthermore, the ticks that were attached to the immunised group could not feed aggressively and dislodged more quickly than those in the control group.
“The vaccine enhances the ability to recognise a tick bite, partially turning a tick bite into a mosquito bite,” explained Fikrig. “When you feel a mosquito bite, you swat it. With the vaccine, there is redness and likely an itch so you can recognise that you have been bitten and can pull the tick off quickly before it has the ability to transmit B. burgdorferi.”
While these findings may be positive, the scientists noted that when three ticks remained attached to the guinea pigs, protection waned in both the vaccinated and non-vaccinated animals. They also cautioned that the vaccine may not be as effective on other organisms. During similar experiments with mice, the team found that vaccinated mice remained unprotected against Lyme disease and failed to acquire natural tick resistance post-infection. According to the team, this may be because mice are a natural reservoir for I. scapularis, causing the ticks to evolve and develop ways to specifically feed repeatedly on mice. Furthermore, the vaccine may have been more potent in guinea pigs because their skin, like human skin, is more layered than that of mice.
In future, human trials will be needed to assess the vaccine’s efficacy in people. But for now, further investigations are expected to examine how proteins in saliva can be manipulated to prevent infection and maximise the vaccine’s efficacy. [APBN]
Source: Sajid et al. (2021). mRNA vaccination induces tick resistance and prevents transmission of the Lyme disease agent. Science Translational Medicine, 13(620).