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

rMERS-CoV-⌬E did not spread in cells in the absence of E protein, thus constituting a single-cycle replicative virus. However, infected cells produced syncytia, which suggests good expression of viral S protein. In addition, high levels of N protein were observed by immunofluorescence. These data suggested that the high expression levels of viral proteins might serve as potent immunogens to elicit a protective immune response. In the case of SARS-CoV, it has been shown that nonreplicating SARS-CoV-like particles bearing the E, S, and membrane (M) proteins induced immune responses that were protective against SARS in mice (47, 48) . In addition, SARS-CoV inactivated viruses induced adaptive immunity that protected against challenge (49) (50) (51) (52) . The potential of rMERS-CoV-⌬E as a vaccine candidate is reinforced by previous observations indicating that a SARS-CoV lacking the E gene (SARS-CoV-⌬E) is attenuated and induces protection in hamsters, transgenic mice, and conventional aged mice (53) (54) (55) .