Middle East Respiratory Syndrome coronavirus (MERS-CoV) has recently emerged as causative agent of severe respiratory disease in humans. Two hundred and six cases of MERS-CoV infection have been confirmed to date, including 71 deaths. Most infections were geographically linked to the Middle East, but cases also occurred in the UK, Germany, France, Italy and Spain. Dromedary camels are likely the reservoir for MERS-CoV virus. The MERS-CoV spike (S) protein, a characteristic structural component of the viral envelope, is considered a key target of vaccines against coronavirus infection, as we and other have previously demonstrated for severe acute respiratory syndrome (SARS) infection. As an initial attempt to develop a MERS-CoV vaccine, we constructed two recombinant adenoviral vectors encoding the full-length MERS-CoV spike (S) protein (Ad5.MERS-S) and the S1 domain of S protein (Ad5.MERS-S1), which mediates binding to the dipeptidyl peptidase 4, which serves as the host cell receptor of MERS-CoV. The safety profile and the growth characteristics of adenoviral-based vaccines make them suitable MERS-CoV vaccine candidates for preclinical testing. Over the past 15 years, we have demonstrated the extraordinary efficacy of adenoviral vaccine platform in eliciting T and B cell-specific responses to the desired antigens and have been involved in developing promising SARS, influenza and RSV vaccines. Here, we hypothesize that subcutaneous (SQ) and/or intranasal administration (IN) of Ad5.MERS vaccines will elicit MERS-CoV-specific immunity, which will lead to the protection of immunized animals. Ultimately our goal is to develop a veterinary vaccine to target dromedary camels. We will test our hypothesis with four specific aims which will: a) test the immunogenicity of the Ad5.MERS vaccine in a mouse model; b) define the optimal immunization schedule and route of administration; c) establish a MERS-CoV challenge model and d) determine the ability of the selected Ad5.MERS vaccine to protect animal from MERS-CoV challenge in the absence of enhanced disease.

Public Health Relevance

A new type of coronavirus has been recently identified as the causative agent underlying a respiratory syndrome that recently emerged in the Middle East. The Coronavirus Study Group of the International Committee on Taxonomy of Viruses proposed a new name for this novel coronavirus: the Middle East Respiratory Syndrome Coronavirus (MERS-CoV). Two hundred and six cases of MERS-CoV infection have been confirmed to date, including 86 deaths. Dromedary camels have shown to be likely the reservoir for MERS-CoV virus. With a mortality rate over 40%, the lack of vaccines against MERS-C0V could become important and serious threat to the human population. Intensive new efforts toward vaccine development are clearly needed to meet the challenge of vaccine and therapeutics development. An ideal MERS-CoV vaccine will induces potent, balanced, and protective cellular and humoral immune responses and is able to provide sterilizing immunity in the animal reservoir (dromedary camels). The development of an effective veterinary MERS-Cov vaccine with the above-mentioned ideal characteristics is the main objective of the proposed studies.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Exploratory/Developmental Grants (R21)
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Special Emphasis Panel (ZRG1)
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Stemmy, Erik J
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University of Pittsburgh
Schools of Medicine
United States
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