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Principal Investigator: Erol Fikrig
Organization: L2 DIAGNOSTICS, LLC
Fiscal Year: 2024
Award: $299,969
Funding agency: National Institute of Allergy and Infectious Diseases
PROJECT SUMMARY
Chikungunya is an arboviral disease transmitted to humans by infected mosquitoes, primarily
the Aedes aegypti and Aedes albopictus species. The virus responsible for the disease is the
chikungunya virus (CHIKV), a member of the Togaviridae family. First identified in Tanzania in
1952, chikungunya has since been reported in over 60 countries in Asia, Africa, Europe, and the
Americas. The symptoms of chikungunya typically include febrile illness, joint pain, nausea,
fatigue, and rash. While the fever usually subsides within a week and the disease is rarely fatal,
joint pain can be severe and debilitating, often lasting for weeks or years.
There is no specific antiviral treatment for chikungunya; care is based on relieving symptoms,
such as with anti-pyretics, optimal analgesics, and fluids. Prevention relies on avoiding mosquito
bites using repellents, wearing long sleeves and trousers, and eliminating standing water where
mosquitoes breed. Vaccine against CHIKV is urgently needed. Only one vaccine has achieved
approval, Valneva's IxchiqTM, which is based on a live attenuated CHIKV. This vaccine undergone
an accelerated regulatory approval by FDA with limited human clinical efficacy study.
Many mosquito salivary proteins were shown to have pro-viral activity and can augment virus
transmission during blood feeding. We have found a mosquito salivary protein, AgBR1, that can
enhance viral transmission and shown that immunization with AgBR1 is protective against several
flaviviruses. Specifically, vaccination of mice with recombinant AgBR1 is protective against Zika,
and passive transfer of AgBR1 antiserum is protective against West Nile disease.
In this proposal, we seek to confirm that AgBR1 vaccine is also protective against Aedes-
transmitted arbovirus of the alphavirus genera, the CHIKV. We will perform comparative
evaluation of different AgBR1 formulation, either recombinant protein or mRNA-LNP vaccine, in
preventing mosquito-borne CHIKV infection in mice. To ascertain the effectiveness of our vaccine
against CHIKV transmission, we will run our test on two murine model of CHIKV infection – (1) an
acute lethal infection model of immunocompromised mouse to see protective effect of the vaccine
against lethal infection, and (2) adult immunocompetent mice to see protective effect of the
vaccine against disease morbidity such as joint pain and arthritis. Our ultimate goal is to generate
a universal vaccine against several mosquito-borne diseases.
Terms: <21+ years old><Acceleration><Active Immunization><Active vaccination><Acute><Adjuvant><Adult><Adult Human><Aedes><Africa><Alpha Virus><Americas><Analgesic Agents><Analgesic Drugs><Analgesic Preparation><Analgesics><Anodynes><Antibodies><Antigens><Antinociceptive Agents><Antinociceptive Drugs><Antisera><Arboviral><Arboviruses><Arthralgia><Arthritis><Arthropod-Borne Viruses><Asia><Attenuated><Benchmarking><Best Practice Analysis><Biological><Bite><Blood><Blood Reticuloendothelial System><Blood Serum><Body Tissues><Borrelia><Breeding><CHIKV><CHIKV infection><Caring><Cavia><Cell Body><Cells><Cephalalgia><Cephalgia><Cephalodynia><Chikungunya virus><Clinical><Clinical Trials><Clinical effectiveness><Country><Cranial Pain><Cricetinae><Culicidae><Data><Disease><Disorder><Dose><Effectiveness><Egypt 101 virus><Europe><Evaluation><Exanthem><Exanthema><Family><Fatigue><Fever><Flavivirus><Flavivirus Infections><Formulation><Goals><Group A Arboviruses><Group B Arbovirus><Guinea Pigs><Guinea Pigs Mammals><Hamsters><Hamsters Mammals><Head Pain><Headache><Histology><Human><Hydrogen Oxide><Immune Sera><Immunization><Immunize><Immunochemical Immunologic><Immunocompetent><Immunocompromised><Immunocompromised Host><Immunocompromised Patient><Immunodeficient Mouse><Immunologic><Immunological><Immunologically><Immunologics><Immunosuppressed Host><Infection><Joint Pain><Joints><Lack of Energy><Leishmania><Liquid substance><Macaca><Macaque><Messenger RNA><Mice><Mice Mammals><Modality><Modeling><Modern Man><Morbidity><Morbidity - disease rate><Mosquito-borne disease><Mosquito-borne infectious disease><Mosquitoes><Murine><Mus><NIH><National Institutes of Health><Nausea><Orthoflavivirus><Passive Immunization><Pathogenesis><Peripheral><Phase><Physiologic><Physiological><Prevention><Program Development><Proteins><Pyrexia><Rash><Recombinant Proteins><Recombinants><Regimen><Reporting><Running><Saliva><Salivary Gland Proteins><Salivary Proteins><Schedule><Serum><Skin Rash><Swelling><Symptoms><Tanzania><Testing><Tissues><Togaviridae><Togaviruses><Transmission><United States National Institutes of Health><Vaccination><Vaccine Design><Vaccines><Viral><Viral Diseases><Viremia><Virus><Virus Diseases><WNV><Water><West Nile><West Nile virus><ZIKA><ZIKV><ZIKV infected><ZIKV infection><ZIKV positive><Zika Virus><Zika virus infection><adulthood><alleviate symptom><ameliorating symptom><antipyretic><arboviral disease><arbovirus disease><arthritic><arthropod transmission><arthropod transmitted><arthropod-borne><arthropod-borne disease><arthropodborne><arthropodborne disease><attenuate><attenuates><benchmark><biologic><borrelial><chikungunya><chikungunya infection><chikungunya virus infection><clinical efficacy><communicable disease transmission><comparative><decrease symptom><determine efficacy><develop a vaccine><develop vaccines><development of a vaccine><disease transmission><efficacy analysis><efficacy assessment><efficacy determination><efficacy evaluation><efficacy examination><efficacy study><evaluate efficacy><examine efficacy><febrile><febris><feeding><fewer symptoms><fluid><head ache><immune competent><immune serum><immunogen><immunogenic><immunosuppressed patient><improved><infected with CHIKV><infected with ZIKV><infected with chikungunya><infected with zika><infectious disease transmission><liquid><mRNA><mRNA lipid nano particle vaccine><mRNA-LNP based vaccine><mRNA-LNP combination vaccines><mRNA-LNP vaccines><member><mosquito-borne><mosquitoborne><mouse model><murine model><neutralizing antibody><non-human primate><nonhuman primate><pain killer><pain medication><pain reliever><painkiller><passive vaccination><pathogen><phase 2 study><phase II study><prevent><preventing><protective effect><reduce symptoms><relieves symptoms><response><success><symptom alleviation><symptom reduction><symptom relief><transmission process><universal vaccine><vaccine candidate><vaccine development><vector><vector-based vaccine><viraemia><viral infection><viral sepsis><viral transmission><virus infection><virus transmission><virus-induced disease><virusemia><zika infected><zika infection><zika viral infection><zikav>