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Principal Investigator: Erol Fikrig
Organization: L2 DIAGNOSTICS, LLC
Fiscal Year: 2024
Award: $298,362
Funding agency: National Institute of Allergy and Infectious Diseases
ABSTRACT
This Phase I proposal seeks to improve a novel vaccine for human use against pathogens
transmitted by the blacklegged tick, Ixodes scapularis. In previous studies, we proposed
that vaccine targeting of tick salivary proteins (Salps) critical for tick feeding would impair
tick feeding and consequently thwart the transmission of multiple tick-borne pathogens.
Our hypothesis is validated by the phenomenon of acquired tick-resistance wherein, upon
repeated tick infestations non-natural hosts such as rabbits, and guinea pigs mount a
robust immune response against tick Salps critical for tick feeding and this results in rapid
rejection of ticks and also prevents transmission of B. burgdorferi. Exploiting this
phenomenon, we identified several Salps that are avidly recognized by tick-resistant
animal sera.
Previous studies have successfully defined a 19Salp-mRNA (19ISP) cocktail that impairs
tick feeding, reduces tick engorgement, and blocks transmission of B. burgdorferi. These
results are now published in the journal Science Translational Medicine (Sajid et al, 2021,
13, eajb9827). Further experiments showed that a 12 mRNA-LNP subset is sufficient to
prevent tick feeding. However, erythema at the tick bite site in immunized animals raises
issues with the safety and commercial success of this experimental vaccine. In
preliminary experiments we have demonstrated that erythema is not sufficient to provoke
tick rejection. In this proposal we will further refine the antigen cocktail by eliminating
those antigens responsible for erythema and define a multiantigen mRNA vaccine that
blocks tick feeding and transmission of tickborne pathogens while eliciting no local
erythema at the bite site.
Terms: <A phagocytophila><A phagocytophilum><A. phagocytophila><A. phagocytophilum><Amblyomma><Anaplasma phagocytophila><Anaplasma phagocytophilum><Anaplasmosis><Animals><Antibody titer measurement><Antigens><B burgdorferi><B miyamotoi><B. burgdorferi><B. miyamotoi><Babesia infection><Babesia microti><Babesia parasite infection><Babesiosis><Bite><Black-legged Tick><Borrelia burgdorferi><Borrelia burgdorferi sensu stricto><Borrelia miyamotoi><Borreliella burgdorferi><Cavia><Cytoecetes phagocytophila><Deer Tick><Dermacentor><Disease><Disorder><Domestic Rabbit><Dose><Ehrlichia equi><Ehrlichia infection><Ehrlichia phagocytophila><Ehrlichiosis><Encapsulated><Erythema><Formulation><Frequencies><Genetic Predisposition><Genetic Predisposition to Disease><Genetic Susceptibility><Genetic propensity><Geography><Goals><Guinea Pigs><Guinea Pigs Mammals><HGE Agent><Hard Ticks><Hardbacked Ticks><Human><I scapularis><I. scapularis><Immune response><Immunization><Immunize><Immunochemical Immunologic><Immunodominant Antigens><Immunologic><Immunological><Immunological response><Immunologically><Immunologics><Impairment><Incidence><Individual><Inherited Predisposition><Inherited Susceptibility><Intramuscular><Ix scalpularis><Ix. scapularis><Ixodes dammini><Ixodes scapularis><Ixodid ticks><Ixodida><Ixodidae><Journals><Lyme Borreliosis><Lyme Disease><Lyme Disease Spirochete><Magazine><Measures><Messenger RNA><Modeling><Modern Man><Oryctolagus cuniculus><OspA><OspA protein><OspA vaccine><Phase><Phase I Study><Phase III study><Piroplasmosis><Powassan><Powassan virus><Prevention><Publishing><Rabbits><Rabbits Mammals><Reaction><Regimen><Resistance><Route><Safety><Salivary><Salivary Gland Proteins><Salivary Proteins><Site><System><Techniques><Tick Infestations><Tick-Borne Infections><Ticks><Translational Research><Translational Science><Transmission><Vaccines><Viral><Viral Diseases><Virus Diseases><Weight><anti-tick immunization><anti-tick vaccine><antibody titering><arthropod transmission><arthropod transmitted><arthropod-borne><arthropodborne><blacklegged tick><cross reactivity><deliver vaccines><determine efficacy><develop a vaccine><develop vaccines><development of a vaccine><dosage><efficacy analysis><efficacy assessment><efficacy determination><efficacy evaluation><efficacy examination><evaluate efficacy><examine efficacy><experiment><experimental research><experimental study><experiments><genetic etiology><genetic mechanism of disease><genetic vulnerability><genetically predisposed><hard-bodied ticks><host response><human pathogen><immune system response><immunization against ticks><immunogen><immunoresponse><improved><infected with Babesia><infected with Ehrlichia><infested with ticks><lipid based nanoparticle><lipid nanoparticle><lyme spirochete><mRNA><mRNA lipid nano particle vaccine><mRNA-LNP based vaccine><mRNA-LNP combination vaccines><mRNA-LNP vaccines><new vaccines><next generation vaccines><non-human primate><nonhuman primate><novel><novel vaccines><outer surface protein A><pathogen><phase 1 study><phase 2 study><phase 3 study><phase II study><prevent><preventing><resistant><response><success><tick bite><tick blood feeding><tick blood meal><tick bloodmeal><tick fed><tick feeding><tick imbibes><tick infested><tick mediated transmission><tick transmission><tick transmitted><tick-borne pathogen><tickborne infection><tickborne pathogen><translation research><translational investigation><translational medicine><transmission blocking><transmission process><vaccine against ticks><vaccine delivery><vaccine development><vaccine efficacy><vaccine safety><vector><viral infection><virus infection><virus-induced disease><weights>