Abstract
ABSTRACT The recently identified Middle East Respiratory Syndrome Coronavirus (MERS-CoV) causes severe and fatal acute respiratory illness in humans. However, no approved prophylactic and therapeutic interventions are currently available. The MERS-CoV envelope spike protein serves as a crucial target for neutralizing antibodies and vaccine development, as it plays a critical role in mediating viral entry through interactions with the cellular receptor, dipeptidyl peptidase 4 (DPP4). Here, we constructed a recombinant rare serotype of the chimpanzee adenovirus 68 (AdC68) that expresses full-length MERS-CoV S protein (AdC68-S). Single intranasal immunization with AdC68-S induced robust and sustained neutralizing antibody and T cell responses in BALB/c mice. In a human DPP4 knock-in (hDPP4-KI) mouse model, it completely protected against lethal challenge with a mouse-adapted MERS-CoV (MERS-CoV-MA). Passive transfer of immune sera to naïve hDPP4-KI mice also provided survival advantages from lethal MERS-CoV-MA challenge. Analysis of sera absorption and isolated monoclonal antibodies from immunized mice demonstrated that the potent and broad neutralizing activity was largely attributed to antibodies targeting the receptor binding domain (RBD) of the S protein. These results show that AdC68-S can induce protective immune responses in mice and represent a promising candidate for further development against MERS-CoV infection in both dromedaries and humans.
Highlights
The outbreaks of MERS-CoV in Saudi Arabia in 2012 and SARS-CoV in China in 2003 introduced two highly pathogenic coronaviruses into the human population [1,2]
These results show that AdC68-S can induce protective immune responses in mice and represent a promising candidate for further development against MERS-CoV infection in both dromedaries and humans
Through a series of serum absorption and monoclonal antibody isolation from immunized animals, we show that the potent and broad neutralizing activity in immunized animals is largely attributed to antibodies targeting the receptor binding domain (RBD) of the S protein
Summary
The outbreaks of MERS-CoV in Saudi Arabia in 2012 and SARS-CoV in China in 2003 introduced two highly pathogenic coronaviruses into the human population [1,2]. As of February, 2019, 2374 confirmed cases of MERS and 823 associated deaths were reported with an estimated fatality rate as high as 35% [4]. Like that of SARS infection [5], asymptomatic MERS cases have been reported [6] suggesting that disease development is likely dependent upon health status and possibly genetics of the infected individual. There are still ongoing reports of human MERS-CoV infections in the affected regions. Many are linked to direct contact with dromedaries, which are believed to be a major reservoir host for MERS-CoV and the immediate source of human infection [7,8]. As dromedaries are critical livestock and vital means of transportation in the affected
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