Engineering a Replication-Competent, Propagation-Defective Middle East Respiratory Syndrome Coronavirus as a Vaccine Candidate

Almazán, Fernando; DeDiego, Marta L.; Sola, Isabel; Zuñiga, Sonia; Nieto-Torres, Jose L.; Marquez-Jurado, Silvia; Andrés, German; Enjuanes, Luis

Vaccines based on live attenuated viruses may present biosafety problems associated with the possibility of reversion to virulent phenotypes or causing disease in immunocompromised individuals. In this sense, the use of rMERS-CoV-⌬E would be a safer option, as it does not propagate in the absence of E protein expression, preventing straightforward reversion to virulence. To increase the biosafety of a rMERS-CoV-⌬E-based vaccine, additional safety guards could be included, such as the previously de-scribed attenuating mutations in distant genomic locations, like those encoding the nsp1 (56, 57) or nsp14 (58) replicase proteins, or by introducing genomic rearrangements (59) . Overall, we consider rMERS-CoV-⌬E a promising vaccine candidate that should be further developed.