Mapping MERS-CoV Immune Responses: A Blueprint for Rational Vaccine Design

Our approach to emerging infections has generally been a reactive post-emergence response, hampering the availability of intervention measures in due time to have substantial impact on outbreaks. Due to the time it takes to develop, test and license a vaccine candidate which can take years, we mostly miss the peak of an outbreak which can last for weeks to months. The presence of licensed platforms that can be deployed in outbreaks for the rapid generation of therapeutic antibodies and vaccines can reduce the time to develop these countermeasures. This will allow the timely supply of therapeutic and preventive products for emerging viruses, thereby limiting their spread and reducing the human and economic toll. In this thesis, the development of platforms for the rapid generation of countermeasures for an emerging zoonotic coronavirus, Middle East respiratory syndrome coronavirus (MERS-CoV), was addressed as part of a zoonotic preparedness approach. The approach implemented for vaccine design was an immunecorrelate- guided approach, whereby we developed and validated assays to identify key viral immunogenic subunits. This was followed by further characterization of these immunogenic domains using specific single domain antibodies (VHHs). Following that, vaccine candidates were rationally designed and tested for their protective efficacy in animal models. This process involved the development of platforms for rapid generation of serological assays, VHHs and HCAbs, as well as subunit protein immunogens. These platforms can be the basis for the rapid development of diagnostics, therapeutics and vaccines for future emerging viruses.

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