The Protective Efficacy of Single-Dose Nasal Immunization with Cold-Adapted Live-Attenuated MERS-CoV Vaccine against Lethal MERS-CoV Infections in Mice.

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe diseases in humans. Camels act as intermediate hosts for MERS-CoV. Currently, no licensed vaccine is available for this virus. We have developed a potential candidate vaccine for MERS-CoV using the cold adaptation method. We cultivated the vaccine in Vero cells at temperatures as low as 22 °C. This live-attenuated vaccine virus showed high attenuation levels in transgenic mice with the MERS-CoV human receptor, dipeptidyl peptidase 4 (DPP4) (K18-hDPP4). The inoculated K18-hDPP4 mice exhibited no clinical signs such as death or body weight loss. Furthermore, no traces of infectious virus were observed when the tissues (nasal turbinate, brain, lung, and kidney) of the K18-hDPP4 mice infected with the cold-adapted vaccine strain were tested. A single intranasal dose of the vaccine administered to the noses of the K18-hDPP4 mice provided complete protection. We did not observe any deaths, body weight loss, or viral detection in the tissues (nasal turbinate, brain, lung, and kidney). Based on these promising results, the developed cold-adapted, attenuated MERS-CoV vaccine strain could be one of the candidates for human and animal vaccines.