Superior immune responses induced by intranasal immunization with recombinant adenovirus-based vaccine expressing full-length Spike protein of Middle East respiratory syndrome coronavirus.

Superior immune responses induced by intranasal immunization with recombinant adenovirus-based vaccine expressing full-length Spike protein of Middle East respiratory syndrome coronavirus.

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Middle East respiratory syndrome coronavirus (MERS-CoV) causes an acute and severe lower respiratory illness as well as vomiting, diarrhea, and renal failure.Because no licensed MERS-CoV vaccines are currently available, preventive and therapeutic Gazebo Tops measures are urgently needed.The surface spike (S) glycoprotein of MERS-CoV, which binds to the cellular receptor dipeptidyl peptidase 4 (DPP4), is considered as a major target for MERS-CoV vaccine development.Here, we designed recombinant replication-deficient adenovirus-based vaccines expressing the N-terminal domain (rAd/NTD) and receptor-binding domain (rAd/RBD) of the MERS-CoV S1 subunit and full-length Spike protein (rAd/Spike).We found that immunization with candidate vaccines via intranasal route induced S1-specific IgG antibodies and neutralizing antibodies against MERS spike pseudotyped virus.

Especially, rAd/Spike induced the highest neutralizing antibody titer and the strongest cytokine-induced T cell responses among the three candidate vaccines.To compare the immune responses induced by different administration routes, rAd/Spike was administered via intranasal, sublingual, or intramuscular route.All these administration routes exhibited neutralizing effects in the serum.MERS-CoV-specific neutralizing IgA antibodies in the bronchoalveolar lavage fluid were only induced by intranasal and sublingual administration but not by intramuscular administration.Intranasal administration with rAd/Spike also created resident memory CD8 T cells in the airway and lung parenchyma.

Taken together, our results showed that Dog Suppliers both the humoral and cellular immune responses are highly induced by rAd/Spike administration, suggesting that rAd/Spike may confer protection against MERS-CoV infection.