A newly developed messenger RNA (mRNA) vaccine is the first such approach to elicit acquired resistance against the tick Ixodes scapularis and prevent it from transmitting the Lyme disease vector Borrelia burgdorferi in guinea pigs, according to a U.S. study led by researchers at Yale University School of Medicine in New Haven, Conn.
The study findings indicate that the new vaccine may either be used alone or in combination with traditional pathogen-based vaccines for preventing Lyme disease and potentially other tick-borne infections, the authors reported in the November 17, 2021, edition of Science Translational Medicine.
Given the general lack of success in developing single, pathogen-specific vaccines against Lyme disease and other tick-borne infections, the development of a broad-spectrum anti-tick vaccine strategy would be highly desirable.
"Vaccines that are both pathogen-specific and tick-resistant are not mutually exclusive," said lead researcher Erol Fikrig, a professor and chief of the Section of Infectious Diseases at Yale.
"Indeed, no vaccine is 100% effective and a combination of the two approaches might make a vaccine that is more effective than either one individually," Fikrig told BioWorld Science.
"The [newly developed] anti-tick mRNA vaccine has the additional potential advantage of perhaps being effective against more than one pathogen, although that remains to be demonstrated."
A possible approach to developing such a vaccine involves developing new methods to detect ticks early and prevent them from feeding.
Animals can develop acquired tick resistance or immunity, which is associated with the recruitment of histamine-secreting inflammatory cells such as basophils to the tick bite site.
Moreover, the dermal hypersensitivity seen after repeated tick bites in humans suggests an association with acquired resistance to I. scapularis, which has also been observed in animals, including guinea pigs.
In guinea pigs, tick immunity protects against I. scapularis-transmitted B. burgdorferi infection, thus an improved understanding of this process may lead to new vaccines against tick-borne infections.
Guinea pigs naturally acquire robust tick immunity after repeated infestations, which are thought to be associated with host immune responses to tick antigens secreted via saliva.
Specific I. scapularis salivary proteins have functional properties that can influence host immune responses, inflammation and coagulation, but it remains unclear whether these are directly involved in generating tick immunity.
Although several tick antigens have been shown to generate a host response, either after a bite or upon specific immunization, robust tick immunity has not been replicated.
Therefore, an approach that replicates the response seen in naturally acquired tick immunity is needed to interfere with pathogen transmission.
For their new study, the authors selected 19 salivary proteins according to high immunogenicity and mostly known mode of action, based on a previous analysis of the tick sialome, the set of mRNAs and proteins expressed in salivary glans.
Nucleoside-modified mRNAs encoding the 19 I. scapularis proteins (19ISP) were then encapsulated in lipid nanoparticles (LNPs) to prevent mRNA degradation and facilitate in vivo delivery.
The nucleoside-modified mRNA-LNP vaccination platform has previously shown promising results for infectious diseases in humans, notably in COVID-19 vaccine trials.
The ability of the new LNP 19ISP vaccine to enhance tick bite recognition and reduce I. scapularis engorgement on a host, thereby preventing B. burgdorferi infection, was then demonstrated in guinea pigs, which were immunized and then challenged with I. scapularis.
Animals given 19ISP were seen to develop erythema at the bite site shortly after tick attachment, which is significant, as it indicates that, "if humans can readily detect a tick bite, they will likely be able to remove the ticks quickly," said Fikrig.
Moreover, compared with untreated controls, in vaccinated mice the ticks fed poorly, as shown by significantly earlier tick detachment and decreased engorgement weights.
In addition, B. burgdorferi transmission was shown to be significantly impeded, with "100% protection being observed when the ticks were removed when redness was first noted," Fikrig said.
This observed effective early induction of local erythema after tick attachment and the ticks' inability to feed normally suggest that 19ISP may either be used alone or in conjunction with conventional pathogen-based vaccines to prevent Lyme disease and possibly other tick-borne infections.
"We are now working on testing in other animal models of tick immunity, and doing studies to determine whether humans who have had tick-borne infections have evidence of antibodies to any of the proteins in our 19ISP cocktail," said Fikrig.
Meanwhile, "we are determining which of the antigens in the 19 antigen cocktail is responsible for tick immunity and testing protection against other pathogens, such as [the tick-borne malaria-like disease] Babesia microti."