Investigation on the immunological cross-protection between different human coronaviruses

Coronaviruses came to global attention as significant human pathogens following the SARS outbreak in 2003. There are six coronaviruses that can cause human disease, viz. 229E, OC43, NL63, HKU1, MERS-CoV, SARS-CoV. MERS coronavirus (MERS-CoV) is the most recent coronavirus to emerge to threaten global public health. Little is known about the immunological cross-protection between these human coronaviruses. Most adults have been infected with multiple endemic human coronaviruses such as 229E, OC43, NL63, HKU1. While it is known that there is little serological cross-neutralization between there viruses, the role of cell mediated immune cross protection between coronaviruses is not known. If such cross-protection does exist, then pre-existing human coronavirus immunity may affect clinical outcomes following exposure to emerging viruses such as MERS or SARS-CV. Alternatively, does prior immunity enhance disease, as may sometimes occur with coronaviruses such as feline infectious peritonitis and flaviviruses such as dengue? What are the antibody mediated and cell mediated immune mechanisms by which such cross-protection or disease enhancement (if any) is mediated? These questions are addressed in this research proposal. Understanding these key knowledge gaps are relevant for understanding the epidemiology and pathogenesis of these important disease-causing viruses of humans and is relevant for development of vaccines against SARS and MERS-CoV.