Chikungunya virus (CHIKV) is an emerging infectious disease virus that has caused large scale outbreaks in the last decade, some of these are ongoing. The cost of decade long chikungunya outbreak, including medical and productivity loss, runs in billions of dollars. There are no licensed CHIKV vaccine or specific threapeutic drugs against CHIKV. United States Army had developed a live attenuated strain of CHIKV, CHIKV181/25, which in spite of demonstrating excellent immunogenicity failed in clinical trials due to residual virulence in some of the vaccinees. Similar outcome of residual virulence has also been reported in some other cases of attenuated alphavirus vaccine candidates. Therefore, it is unlikely that a live attenuated alphavirus will get FDA approval as vaccine for human application. There is a renewed focus on generating inactivated or highly attenuated chimeric CHIKV vaccine candidates. In this study, a novel approach for generating ?-radiation-inactivated CHIKV vaccine will be tested ?-radiation. Hypothesis will be tested first by evaluating the complete inactivation of CHIKV in cell culture, and in-vivo in sensitive neonatal mice, so as to rule out the protection of infectivity of CHIKV by MDP complex during exposure with ?-radiation. Second, epitope integrity of inactivated CHIKV will be evaluated using monoclonal antibodies against the virus envelope glycoproteins. Immunogenic potential in terms of induction of anti-CHIKV antibody will be evaluated in immunocompetent C57BL6 mice. Protective efficacy of inactivated CHIKV will be evaluated in- vivo in adult A129 (IFN?/?R-/-) mice model of CHIKV infection. Single immunization potential of inactivated CHIKV will also be evaluated. CHIKV infections spread rapidly during an outbreak. Single immunization will result in short and thereby, better adherence to immunization regimen that would be needed to develop protective immunivty against the virus, and will help in fighting the explosive nature of CHIKV outbreak. Long-term goal of the proposed research is to develop a safe and effective CHIKV-vaccine candidate. The current ongoing outbreak of CHIKV has shown potential to spread to the previously CHIKV-nave regions of the globe such as the North Americas. In absence of an effective anti-CHIKV drug, vaccine, and any herd immunity in its population, CHIKV outbreak in the contiguous North Americas will be devastating.

Public Health Relevance

Chikungunya virus (CHIKV) has affected millions of individuals across the tropical countries. CHIKV infection has been detected in the USA and chances of a bigger outbreak of CHIKV in continental USA are high. There is no FDA-approved vaccine for CHIKV, therefore, a safe and effective vaccine is urgently needed. This study proposes to develop a safe and efficient inactivated-CHIKV vaccine using a novel method.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Exploratory/Developmental Grants (R21)
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Vaccines Against Microbial Diseases Study Section (VMD)
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Repik, Patricia M
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Henry M. Jackson Fdn for the Adv Mil/Med
Research Institutes
United States
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