The Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic betacoronavirus that was first detected in humans in 2012 as a cause of severe acute respiratory disease. As of July 28, 2017, there have been 2,040 confirmed cases with 712 reported deaths. While many
infections have been fatal, there have also been a large number of mild or asymptomatic cases discovered through monitoring and contact tracing. New Zealand white rabbits are a possible model for
asymptomatic infection with MERS-CoV. In order to discover more about non-lethal
infections and to learn whether a single
infection with MERS-CoV would protect against
reinfection, we inoculated rabbits with MERS-CoV and monitored the antibody and inflammatory response. Following intranasal
infection, rabbits developed a transient dose-dependent pulmonary
infection with moderately high levels of
viral RNA,
viral antigen, and perivascular
inflammation in multiple lung lobes that was not associated with clinical signs. The rabbits developed
antibodies against
viral proteins that lacked neutralizing activity and the animals were not protected from
reinfection. In fact,
reinfection resulted in enhanced
pulmonary inflammation, without an associated increase in
viral RNA titers. Interestingly, passive transfer of serum from previously infected rabbits to naïve rabbits was associated with enhanced
inflammation upon
infection. We further found this
inflammation was accompanied by increased recruitment of
complement proteins compared to primary
infection. However,
reinfection elicited
neutralizing antibodies that protected rabbits from subsequent viral challenge. Our data from the rabbit model suggests that people exposed to MERS-CoV who fail to develop a
neutralizing antibody response, or persons whose
neutralizing antibody titers have waned, may be at risk for severe
lung disease on re-exposure to MERS-CoV.