MERS-CoV causes lethal infection in humans, and there is no vaccine. Our work demonstrates that PIV5 is a promising vector for developing a MERS vaccine. Furthermore, success of PIV5-based MERS vaccine can be employed to develop a vaccine for emerging CoVs such as SARS-CoV-2, which causes COVID-19. ABSTRACT Middle East respiratory syndrome coronavirus (MERS-CoV) can cause severe and fatal acute respiratory disease in humans and remains endemic in the Middle East since first being identified in 2012. There are currently no approved vaccines or therapies available for MERS-CoV. In this study, we evaluated parainfluenza virus 5 (PIV5)-based vaccine expressing the MERS-CoV envelope spike protein (PIV5/MERS-S) in a human DPP4 knockin C57BL/6 congenic mouse model (hDPP4 KI). Following a single-dose intranasal immunization, PIV5-MERS-S induced neutralizing antibody and robust T cell responses in hDPP4 KI mice. A single intranasal administration of 10 4 PFU PIV5-MERS-S provided complete protection against a lethal challenge with mouse-adapted MERS-CoV (MERS MA 6.1.2) and improved virus clearance in the lung. In comparison, single-dose intramuscular immunization with 10 6 PFU UV-inactivated MERS MA 6.1.2 mixed with Imject alum provided protection to only 25% of immunized mice. Intriguingly, an influx of eosinophils was observed only in the lungs of mice immunized with inactivated MERS-CoV, suggestive of a hypersensitivity-type response. Overall, our study indicated that PIV5-MERS-S is a promising effective vaccine candidate against MERS-CoV infection.
【저자키워드】 COVID-19, Vaccine, coronavirus, MERS, 【초록키워드】 neutralizing antibody, SARS-CoV-2, therapy, Human, lung, MERS-CoV, immunization, eosinophil, Spike protein, mice, humans, vaccine candidate, CoV, parainfluenza virus, T cell response, intranasal, inactivated, intramuscular, Endemic, administration, acute respiratory disease, Middle East, virus clearance, respiratory syndrome coronavirus, MERS-CoV infection, immunized mice, lethal infection, C57BL/6, Complete, hDPP4, effective, immunized, robust, develop, indicated, evaluated, approved, provided, cause, expressing, human DPP4, 【제목키워드】 coronavirus, spike, MERS-CoV, respiratory, recombinant, Middle East,