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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; 14(7):e0220196.Plos

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.

Authors+Show Affiliations

Graduate School of Pharmaceutical Sciences, Ewha Woman's University, Seoul, Republic of Korea.Department of Otorhinolaryngology, Seoul National University College of Medicine, Seoul, Republic of Korea.Graduate School of Pharmaceutical Sciences, Ewha Woman's University, Seoul, Republic of Korea.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31329652

Citation

Kim, Myung Hee, et al. "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, vol. 14, no. 7, 2019, pp. e0220196.
Kim MH, Kim HJ, Chang J. 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;14(7):e0220196.
Kim, M. H., Kim, H. J., & Chang, J. (2019). 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, 14(7), e0220196. https://doi.org/10.1371/journal.pone.0220196
Kim MH, Kim HJ, Chang J. 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;14(7):e0220196. PubMed PMID: 31329652.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Superior immune responses induced by intranasal immunization with recombinant adenovirus-based vaccine expressing full-length Spike protein of Middle East respiratory syndrome coronavirus. AU - Kim,Myung Hee, AU - Kim,Hyun Jik, AU - Chang,Jun, Y1 - 2019/07/22/ PY - 2019/02/26/received PY - 2019/07/10/accepted PY - 2019/7/23/entrez PY - 2019/7/23/pubmed PY - 2020/2/27/medline SP - e0220196 EP - e0220196 JF - PloS one JO - PLoS One VL - 14 IS - 7 N2 - 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. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/31329652/Superior_immune_responses_induced_by_intranasal_immunization_with_recombinant_adenovirus_based_vaccine_expressing_full_length_Spike_protein_of_Middle_East_respiratory_syndrome_coronavirus_ L2 - https://dx.plos.org/10.1371/journal.pone.0220196 DB - PRIME DP - Unbound Medicine ER -