Not listed ION CHANNELS AS TARGETS FOR AN ANTI- TICK VACCINE - ABSTRACT: THE PREVALENCE OF TICK-BORNE DISEASES IN THE UNITED STATES IS ON THE RISE, NECESSITATING INNOVATIVE SOLUTIONS. ANTI-TICK VACCINES CAN CONTRIBUTE TO VECTOR CONTROL AND MITIGATE THE SPREAD OF TICK-BORNE ILLNESSES BY INDUCING HOST IMMUNITY TO TARGETS IN TICK SALIVA OR WITHIN THE TICK ITSELF. WHILE THESE APPROACHES HAVE SHOWN SOME SUCCESS, THEY REQUIRE FURTHER OPTIMIZATION. WE PROPOSE AN INNOVATIVE STRATEGY TO ENHANCE THE EFFICACY OF ANTI-TICK VACCINES BY INDUCING ANTIBODIES AGAINST THE TICK ION CHANNELS THAT HAVE TRADITIONALLY BEEN TARGETED BY SMALL MOLECULES. PREVIOUS WORK DEMONSTRATED THAT ANTI-GLUTAMATE GATED CHLORIDE CHANNEL (GLUCL) ANTIBODIES EXHIBITED TOXICITY IN MOSQUITOES BUT WERE LIMITED BY THEIR INABILITY TO EXIT THE MIDGUT AND BIND TO THEIR TARGETS IN THE PERIPHERY. OUR PRELIMINARY DATA REPLICATE THIS TOXICITY IN TICKS. MICROINJECTIONS OF PURIFIED POLYCLONAL ANTIBODIES FROM MICE VACCINATED WITH TICK GLUCL PEPTIDES INDUCED MORTALITY THAT WAS STATISTICALLY INDISTINGUISHABLE FROM THE SMALL MOLECULE POSITIVE CONTROL AND THREE TIMES GREATER THAN THE NEGATIVE CONTROL ANTIBODIES. GLUCL IS EXCEPTIONALLY CONSERVED AMONG TICKS AND IS ABSENT IN VERTEBRATES, MAKING IT A POTENTIAL TARGET FOR BROAD-SPECTRUM TICK CONTROL. TICKS ALLOW ORDERS OF MAGNITUDE MORE ANTIBODY "LEAKAGE" INTO THE HEMOLYMPH COMPARED TO MOSQUITOES, SENSITIZING THEM TO THIS APPROACH. IF THE BASELINE LEVEL OF ANTIBODY LEAKAGE IS INSUFFICIENT, THERE IS A MEANS TO INCREASE GUT LEAKAGE: VACCINATION WITH BM86. BM86 WAS PREVIOUSLY USED AS A COMMERCIAL ANTI-TICK VACCINE AGAINST THE ECONOMICALLY SIGNIFICANT RHIPICEPHALUS MICROPLUS TICK. THIS VACCINATION PROMOTES SUBSTANTIAL LEAKAGE OF THE TICK GUT WHEN FEEDING ON A VACCINATED HOST, ALTHOUGH IT WAS HELD BACK BY ONLY EXERTING THIS EFFECT IN R.MICROPLUS TICKS. AS A PROOF OF CONCEPT, WE PROPOSE COMBINING VACCINATION WITH GLUCL AND BM86 AND CONDUCTING TESTING ON THE R.MICROPLUS TICK AS A MODEL SYSTEM TO ENSURE THAT NATURALLY INGESTED ANTIBODIES AGAINST GLUCL HAVE THE GREATEST OPPORTUNITY TO REACH THEIR TARGET AND EXERT THEIR TOXIC EFFECT. IN PARALLEL, WE PROPOSE SCREENING OTHER TICK ION CHANNELS AS POTENTIAL VACCINE TARGETS TO ASSESS OF TICK-KILLING ANTIBODIES ARE ALSO INDUCED. THIS FELLOWSHIP GRANT AND TRAINING PLAN IS WELL DESIGNED TO PREPARE ME TO BECOME A SUPERLATIVE INFECTIOUS DISEASE PHYSICIAN AND A LEADING EXPERT IN TICKS AND VECTOR CONTROL IN THE UNITED STATES. TICKS AND VECTOR-BORNE DISEASES ARE POISED TO BE A GRAVE PUBLIC HEALTH CONCERN IN THE COMING DECADES AND THERE ARE NOT ENOUGH PHYSICIAN SCIENTISTS TO MEET THE THREAT OF TICK-BORNE DISEASE IN THAT TIME. MY PROJECT, STUDYING TICKS THEMSELVES AND DEVELOPING AN INNOVATIVE MEANS TO CONTROL THEM, CIRCUMVENTS THE HETEROGENEITY OF TICK-BORNE DISEASES BY FOCUSING ON THE VECTORS THAT THESE DIVERSE DISEASES SHARE AS A COMMON MODE OF INTRODUCTION TO HUMANS. BY FUNDING MY FELLOWSHIP, YOU WILL BE INVESTING IN AN INDIVIDUAL WITH A TRACK RECORD OF SUCCESS AND COMMITTED TO DEVELOPING EFFECTIVE WAYS TO PROTECT AMERICANS FROM THE LOOMING THREAT THAT TICK-BORNE DISEASES POSE. $51.5k 8/6/26 Not listed ION CHANNELS AS TARGETS FOR AN ANTI- TICK VACCINE - ABSTRACT: THE PREVALENCE OF TICK-BORNE DISEASES IN THE UNITED STATES IS ON THE RISE, NECESSITATING INNOVATIVE SOLUTIONS. ANTI-TICK VACCINES CAN CONTRIBUTE TO VECTOR CONTROL AND MITIGATE THE SPREAD OF TICK-BORNE ILLNESSES BY INDUCING HOST IMMUNITY TO TARGETS IN TICK SALIVA OR WITHIN THE TICK ITSELF. WHILE THESE APPROACHES HAVE SHOWN SOME SUCCESS, THEY REQUIRE FURTHER OPTIMIZATION. WE PROPOSE AN INNOVATIVE STRATEGY TO ENHANCE THE EFFICACY OF ANTI-TICK VACCINES BY INDUCING ANTIBODIES AGAINST THE TICK ION CHANNELS THAT HAVE TRADITIONALLY BEEN TARGETED BY SMALL MOLECULES. PREVIOUS WORK DEMONSTRATED THAT ANTI-GLUTAMATE GATED CHLORIDE CHANNEL (GLUCL) ANTIBODIES EXHIBITED TOXICITY IN MOSQUITOES BUT WERE LIMITED BY THEIR INABILITY TO EXIT THE MIDGUT AND BIND TO THEIR TARGETS IN THE PERIPHERY. OUR PRELIMINARY DATA REPLICATE THIS TOXICITY IN TICKS. MICROINJECTIONS OF PURIFIED POLYCLONAL ANTIBODIES FROM MICE VACCINATED WITH TICK GLUCL PEPTIDES INDUCED MORTALITY THAT WAS STATISTICALLY INDISTINGUISHABLE FROM THE SMALL MOLECULE POSITIVE CONTROL AND THREE TIMES GREATER THAN THE NEGATIVE CONTROL ANTIBODIES. GLUCL IS EXCEPTIONALLY CONSERVED AMONG TICKS AND IS ABSENT IN VERTEBRATES, MAKING IT A POTENTIAL TARGET FOR BROAD-SPECTRUM TICK CONTROL. TICKS ALLOW ORDERS OF MAGNITUDE MORE ANTIBODY "LEAKAGE" INTO THE HEMOLYMPH COMPARED TO MOSQUITOES, SENSITIZING THEM TO THIS APPROACH. IF THE BASELINE LEVEL OF ANTIBODY LEAKAGE IS INSUFFICIENT, THERE IS A MEANS TO INCREASE GUT LEAKAGE: VACCINATION WITH BM86. BM86 WAS PREVIOUSLY USED AS A COMMERCIAL ANTI-TICK VACCINE AGAINST THE ECONOMICALLY SIGNIFICANT RHIPICEPHALUS MICROPLUS TICK. THIS VACCINATION PROMOTES SUBSTANTIAL LEAKAGE OF THE TICK GUT WHEN FEEDING ON A VACCINATED HOST, ALTHOUGH IT WAS HELD BACK BY ONLY EXERTING THIS EFFECT IN R.MICROPLUS TICKS. AS A PROOF OF CONCEPT, WE PROPOSE COMBINING VACCINATION WITH GLUCL AND BM86 AND CONDUCTING TESTING ON THE R.MICROPLUS TICK AS A MODEL SYSTEM TO ENSURE THAT NATURALLY INGESTED ANTIBODIES AGAINST GLUCL HAVE THE GREATEST OPPORTUNITY TO REACH THEIR TARGET AND EXERT THEIR TOXIC EFFECT. IN PARALLEL, WE PROPOSE SCREENING OTHER TICK ION CHANNELS AS POTENTIAL VACCINE TARGETS TO ASSESS OF TICK-KILLING ANTIBODIES ARE ALSO INDUCED. THIS FELLOWSHIP GRANT AND TRAINING PLAN IS WELL DESIGNED TO PREPARE ME TO BECOME A SUPERLATIVE INFECTIOUS DISEASE PHYSICIAN AND A LEADING EXPERT IN TICKS AND VECTOR CONTROL IN THE UNITED STATES. TICKS AND VECTOR-BORNE DISEASES ARE POISED TO BE A GRAVE PUBLIC HEALTH CONCERN IN THE COMING DECADES AND THERE ARE NOT ENOUGH PHYSICIAN SCIENTISTS TO MEET THE THREAT OF TICK-BORNE DISEASE IN THAT TIME. MY PROJECT, STUDYING TICKS THEMSELVES AND DEVELOPING AN INNOVATIVE MEANS TO CONTROL THEM, CIRCUMVENTS THE HETEROGENEITY OF TICK-BORNE DISEASES BY FOCUSING ON THE VECTORS THAT THESE DIVERSE DISEASES SHARE AS A COMMON MODE OF INTRODUCTION TO HUMANS. BY FUNDING MY FELLOWSHIP, YOU WILL BE INVESTING IN AN INDIVIDUAL WITH A TRACK RECORD OF SUCCESS AND COMMITTED TO DEVELOPING EFFECTIVE WAYS TO PROTECT AMERICANS FROM THE LOOMING THREAT THAT TICK-BORNE DISEASES POSE. $0 8/6/26