mRNA vaccination targeting Amblyomma ticks to prevent alpha gal syndrome

PROJECT SUMMARY/ABSTRACT Acquired tick resistance (ATR) occurs when ticks can no longer feed on a host. This proposal will determine whether ATR can be induced against Amblyomma americanum - the first step in a novel vaccine to prevent red meat allergy. A. americanum tick bites are associated with IgE mediated type I hypersensitivity reactions to galactose-α-1,3-galactose (alpha-gal). Alpha gal is an oligosaccharide unique to many non-primate animals and added during post-translational protein modification. Old world primates including humans (catarrhines) have lost the enzyme and therefore do not possess alpha-gal modified proteins. Once sensitized by an A. americanum tick bite, some humans experience a hypersensitivity response to alpha-gal, known as alpha gal syndrome -- upon consuming specific types of meat or its derived products. Patients who avoid tick bites have been shown to have a decrease in their alpha-gal IgE levels suggesting that inhibiting tick feeding could decrease the production of alpha gal antibodies. ATR, therefore, is a novel strategy to prevent alpha gal syndrome. We demonstrated ATR in guinea pigs against Ixodes scapularis ticks. Further, our group also showed that ATR induced by I. scapularis results in ATR against A. americanum. In addition, we have also reported that a lipid nanoparticle containing the mRNAs for 19 I. scapularis salivary proteins (19ISP) was sufficient to induce ATR against I. scapularis. We have demonstrated that immunity against I. scapularis cement antigens also elicit ATR against I. scapularis in guinea pigs. Our initial observations suggest that lipid nanoparticles containing the mRNAs for 19ISP or predominant cement antigens of I. scapularis may induce ATR against A. americanum. These observations support our hypothesis that an mRNA vaccine can be developed to induce ATR against A. americanum – the first step towards a unique vaccine to prevent alpha gal syndrome. Our hypothesis will be evaluated comprehensively in this proposal.