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

PLoS One. 2019 Jul 22;14(7):e0220196. doi: 10.1371/journal.pone.0220196. eCollection 2019.

Abstract

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 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 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Adenoviridae / immunology
  • Administration, Intranasal
  • Animals
  • Antibodies, Neutralizing / immunology
  • Cells, Cultured
  • Coronavirus Infections / immunology*
  • Coronavirus Infections / prevention & control
  • Female
  • HEK293 Cells
  • Humans
  • Immunoglobulin A / immunology
  • Mice
  • Mice, Inbred BALB C
  • Middle East Respiratory Syndrome Coronavirus / immunology*
  • Spike Glycoprotein, Coronavirus / genetics
  • Spike Glycoprotein, Coronavirus / immunology*
  • Spodoptera
  • Vaccination / methods*
  • Vaccines, Synthetic / genetics
  • Vaccines, Synthetic / immunology

Substances

  • Antibodies, Neutralizing
  • Immunoglobulin A
  • Spike Glycoprotein, Coronavirus
  • Vaccines, Synthetic

Grant support

This study was supported by a grant of the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea [Grant number: HI15C2923].