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Principal Investigator: Joseph Edgar Craft
Organization: YALE UNIVERSITY
Fiscal Year: 2022
Award: $648,095
Funding agency: National Institute of Allergy and Infectious Diseases
PROJECT SUMMARY
A novel vaccine for Lyme disease
Acquired resistance to Ixodes scapularis, commonly known as “tick resistance”,
can prevent transmission of Borrelia burgdorferi, the Lyme disease agent. We have
shown that tick resistance can be generated in guinea pigs (1) repeatedly exposed to I.
scapularis, (2) immunized with I. scapularis saliva, or (3) immunized with a lipid
nanoparticle containing mRNAs encoding 19 saliva proteins (19ISP). In addition,
salivary protein 14 (Salp14), a component of 19ISP, elicits partial tick resistance.
The goal of this proposal is to identify the specific proteins in I. scapularis
saliva that elicit tick resistance and demonstrate that vaccination with these
proteins can prevent B. burgdorferi infection. We will delineate the importance of
Salp14 and additional saliva proteins in tick resistance, determine the host responses
that are associated with tick resistance, and examine whether vaccination with saliva
proteins or mRNAs encoding each saliva protein can prevent B. burgdorferi infection.
These studies will lead to new knowledge to aid in the development of a novel vaccine
which may prevent Lyme disease and, possibly, other tick-borne infections.
Terms: <Animal Model><Animal Models and Related Studies><Animals><Antibody Response><Antigens><B burgdorferi><B. burgdorferi><Black-legged Tick><Blast Transformation><Blastogenesis><Borrelia burgdorferi><Borrelia burgdorferi sensu stricto><Borreliella burgdorferi><CD4 Cells><CD4 Positive T Lymphocytes><CD4 T cells><CD4 helper T cell><CD4 lymphocyte><CD4+ T-Lymphocyte><CD4-Positive Lymphocytes><Cavia><Complement><Complement Proteins><Data><Deer Tick><Dermal><Development><Domestic Rabbit><Ecdysis><Exposure to><Fecundability><Fecundity><Fertility><Goals><Guinea Pigs><Guinea Pigs Mammals><Host Factor><Host Factor Protein><I scapularis><I. scapularis><Immune response><Immunization><Immunize><Immunochemical Immunologic><Immunologic><Immunologic Sensitization><Immunologic Stimulation><Immunological><Immunological Sensitization><Immunological Stimulation><Immunological response><Immunologically><Immunologics><Immunostimulation><Infection><Infection prevention><Integration Host Factors><Ix scalpularis><Ix. scapularis><Ixodes dammini><Ixodes scapularis><Ixodida><Kinetics><Knowledge><Lead><Lyme Borreliosis><Lyme Disease><Lyme Disease Spirochete><Lyme Disease Vaccines><Lymphoblast Transformation><Lymphocyte Activation><Lymphocyte Stimulation><Lymphocyte Transformation><Messenger RNA><Modeling><Molting><Names><Oryctolagus cuniculus><Pathway interactions><Pb element><Play><Post-Transcriptional Gene Silencing><Posttranscriptional Gene Silencing><Prevent infection><Prevention><Process><Proteins><Publishing><Quelling><RNA Interference><RNA Silencing><RNA immunization><RNA vaccination><RNAi><Rabbits><Rabbits Mammals><Reagent><Redness><Resistance><Role><Saliva><Salivary Gland Proteins><Salivary Proteins><Sequence-Specific Posttranscriptional Gene Silencing><Skin><Systemic infection><T4 Cells><T4 Lymphocytes><Tick-Borne Infections><Ticks><Transmission><Vaccination><blacklegged tick><developmental><experiment><experimental research><experimental study><global gene expression><global transcription profile><heavy metal Pb><heavy metal lead><host response><i(19)><immune system response><immunization strategy><immunogen><immunoresponse><in vivo><lipid based nanoparticle><lipid nanoparticle><lyme spirochete><lyme vaccine><lymphocyte proliferation><mRNA><mRNA immunization><mRNA vaccination><model of animal><model organism><nano particle><nano-sized particle><nanoparticle><nanosized particle><new vaccines><next generation vaccines><novel><novel vaccines><pathogen><pathway><prevent><preventing><resistant><response><saliva mediated><social role><tick bite><tick mediated transmission><tick saliva><tick transmission><tick transmitted><tickborne infection><transcriptome><transcriptomics><transmission process><vaccination strategy>