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Effect of Fc Fusion on Folding and Immunogenicity of Middle East Respiratory Syndrome Coronavirus Spike Protein.
J Microbiol Biotechnol. 2019 May 28; 29(5):813-819.JM

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) induces severe respiratory impairment with a reported mortality rate of ~36% in humans. The absence of clinically available MERS-CoV vaccines and treatments to date has resulted in uncontrolled incidence and propagation of the virus. In vaccine design, fusion with the IgG Fc domain is reported to increase the immunogenicity of various vaccine antigens. However, limited reports have documented the potential negative effects of Fc fusion on vaccine antigens. To determine whether Fc fusion affects the immunogenicity of MERS-CoV antigen, we constructed a Fcassociated MERS-CoV spike protein (eS770-Fc, 110 kDa), whereby human IgG4 Fc domain was fused to MERS-CoV spike protein (eS770) via a Gly/Pro linker using baculovirus as the expression system. For comparative analyses, two eS770 proteins lacking the IgG4 Fc domain were generated using the IdeS protease (eS770-ΔFc) or His tag attachment (eS770-His) and the immunogenicity of the above constructs were examined following intramuscular immunization in mice. Contrary to expectations, non-Fc spike proteins (eS770-ΔFc, eS770-His; 90 kDa) showed higher immunogenicity than the Fc fusion protein (eS770-Fc). Moreover, unlike non- Fc spike proteins, eS770-Fc immunization did not elicit neutralizing antibodies against MERSCoV. The lower immunogenicity of Fc-fused eS770 was related to alterations in the structural conformation of the spike protein. Taken together, our results indicate that IgG Fc fusion reduces the immunogenicity of eS770 by interfering with the proper folding structure.

Authors+Show Affiliations

Department of Bio-industrial Technologies, Konkuk University, Seoul 05029, Republic of Korea. Department of Biomedical Science and Engineering, Konkuk University, Seoul 05029, Republic of Korea.Department of Bio-industrial Technologies, Konkuk University, Seoul 05029, Republic of Korea. Department of Biomedical Science and Engineering, Konkuk University, Seoul 05029, Republic of Korea.Department of Bio-industrial Technologies, Konkuk University, Seoul 05029, Republic of Korea. Department of Biomedical Science and Engineering, Konkuk University, Seoul 05029, Republic of Korea.Department of Bio-industrial Technologies, Konkuk University, Seoul 05029, Republic of Korea. Department of Biomedical Science and Engineering, Konkuk University, Seoul 05029, Republic of Korea.Department of Biomedical Science and Engineering, Konkuk University, Seoul 05029, Republic of Korea.Department of Biomedical Science and Engineering, Konkuk University, Seoul 05029, Republic of Korea.WooGene B&G, Seoul, 07299, Republic of Korea.Department of Biotechnology and Bioinformatics, Korea University, Sejong 30019, Republic of Korea.College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826, Republic of Korea.Department of Bio-industrial Technologies, Konkuk University, Seoul 05029, Republic of Korea. Department of Biomedical Science and Engineering, Konkuk University, Seoul 05029, Republic of Korea.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30982320

Citation

Chun, Jungmin, et al. "Effect of Fc Fusion On Folding and Immunogenicity of Middle East Respiratory Syndrome Coronavirus Spike Protein." Journal of Microbiology and Biotechnology, vol. 29, no. 5, 2019, pp. 813-819.
Chun J, Cho Y, Park KH, et al. Effect of Fc Fusion on Folding and Immunogenicity of Middle East Respiratory Syndrome Coronavirus Spike Protein. J Microbiol Biotechnol. 2019;29(5):813-819.
Chun, J., Cho, Y., Park, K. H., Choi, H., Cho, H., Lee, H. J., Jang, H., Kim, K. H., Oh, Y. K., & Kim, Y. B. (2019). Effect of Fc Fusion on Folding and Immunogenicity of Middle East Respiratory Syndrome Coronavirus Spike Protein. Journal of Microbiology and Biotechnology, 29(5), 813-819. https://doi.org/10.4014/jmb.1903.03043
Chun J, et al. Effect of Fc Fusion On Folding and Immunogenicity of Middle East Respiratory Syndrome Coronavirus Spike Protein. J Microbiol Biotechnol. 2019 May 28;29(5):813-819. PubMed PMID: 30982320.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of Fc Fusion on Folding and Immunogenicity of Middle East Respiratory Syndrome Coronavirus Spike Protein. AU - Chun,Jungmin, AU - Cho,Yeondong, AU - Park,Ki Hoon, AU - Choi,Hanul, AU - Cho,Hansam, AU - Lee,Hee-Jung, AU - Jang,Hyun, AU - Kim,Kyung Hyun, AU - Oh,Yu-Kyoung, AU - Kim,Young Bong, PY - 2019/4/16/pubmed PY - 2019/6/18/medline PY - 2019/4/16/entrez KW - IgG Fc domain KW - MERS-CoV KW - immunogenicity KW - protein folding KW - subunit vaccine SP - 813 EP - 819 JF - Journal of microbiology and biotechnology JO - J Microbiol Biotechnol VL - 29 IS - 5 N2 - Middle East respiratory syndrome coronavirus (MERS-CoV) induces severe respiratory impairment with a reported mortality rate of ~36% in humans. The absence of clinically available MERS-CoV vaccines and treatments to date has resulted in uncontrolled incidence and propagation of the virus. In vaccine design, fusion with the IgG Fc domain is reported to increase the immunogenicity of various vaccine antigens. However, limited reports have documented the potential negative effects of Fc fusion on vaccine antigens. To determine whether Fc fusion affects the immunogenicity of MERS-CoV antigen, we constructed a Fcassociated MERS-CoV spike protein (eS770-Fc, 110 kDa), whereby human IgG4 Fc domain was fused to MERS-CoV spike protein (eS770) via a Gly/Pro linker using baculovirus as the expression system. For comparative analyses, two eS770 proteins lacking the IgG4 Fc domain were generated using the IdeS protease (eS770-ΔFc) or His tag attachment (eS770-His) and the immunogenicity of the above constructs were examined following intramuscular immunization in mice. Contrary to expectations, non-Fc spike proteins (eS770-ΔFc, eS770-His; 90 kDa) showed higher immunogenicity than the Fc fusion protein (eS770-Fc). Moreover, unlike non- Fc spike proteins, eS770-Fc immunization did not elicit neutralizing antibodies against MERSCoV. The lower immunogenicity of Fc-fused eS770 was related to alterations in the structural conformation of the spike protein. Taken together, our results indicate that IgG Fc fusion reduces the immunogenicity of eS770 by interfering with the proper folding structure. SN - 1738-8872 UR - https://www.unboundmedicine.com/medline/citation/30982320/Effect_of_Fc_Fusion_on_Folding_and_Immunogenicity_of_Middle_East_Respiratory_Syndrome_Coronavirus_Spike_Protein_ L2 - http://www.jmb.or.kr/journal/view.html?doi=10.4014/jmb.1903.03043 DB - PRIME DP - Unbound Medicine ER -