Enhancing immune protection against MERS-CoV: the synergistic effect of proteolytic cleavage sites and the fusion peptide and RBD domain targeting VLP immunization

Jeein Oh; Uni Park; Juhyung Kim; Kyeongseok Jeon; Chulwoo Kim; Nam-Hyuk Cho; Youn Soo Choi

doi:10.3389/fimmu.2023.1201136

Enhancing immune protection against MERS-CoV: the synergistic effect of proteolytic cleavage sites and the fusion peptide and RBD domain targeting VLP immunization

Front Immunol. 2023 May 19:14:1201136. doi: 10.3389/fimmu.2023.1201136. eCollection 2023.

Authors

Jeein Oh¹, Uni Park², Juhyung Kim¹, Kyeongseok Jeon^{1

2}, Chulwoo Kim³, Nam-Hyuk Cho^{1

2

4}, Youn Soo Choi^{1

5

6}

Affiliations

¹ Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.
² Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Republic of Korea.
³ Deparatment of Microbiology, Institute for Viral Diseases, Korea University College of Medicine, Seoul, Republic of Korea.
⁴ Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, Republic of Korea.
⁵ Department of Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
⁶ Transplantation Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.

Abstract

Introduction: The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is a zoonotic infectious virus that has caused significant outbreaks in the Middle East and beyond. Due to a highly mortality rate, easy transmission, and rapid spread of the MERS-CoV, it remains as a significant public health treat. There is currently no licensed vaccine available to protect against MERS-CoV.

Methods: In this study, we investigated whether the proteolytic cleavage sites and fusion peptide domain of the MERS-CoV spike (S) protein could be a vaccine target to elicit the MERS-CoV S protein-specific antibody responses and confer immune protection against MERS-CoV infection. Our results demonstrate that immunization of the proteolytic cleavage sites and the fusion peptide domain using virus-like particle (VLP) induced the MERS-CoV S protein-specific IgG antibodies with capacity to neutralize pseudotyped MERS-CoV infection in vitro. Moreover, proteolytic cleavage sites and the fusion peptide VLP immunization showed a synergistic effect on the immune protection against MERS-CoV infection elicited by immunization with VLP expressing the receptor binding domain (RBD) of the S protein. Additionally, immune evasion of MERS-CoV RBD variants from anti-RBD sera was significantly controlled by anti-proteolytic cleavage sites and the fusion peptide sera.

Conclusion and discussion: Our study demonstrates the potential of VLP immunization targeting the proteolytic cleavage sites and the fusion peptide and RBD domains of the MERS-CoV S protein for the development of effective treatments and vaccines against MERS-CoV and related variants.

Keywords: MERS-CoV; PSFP; RBD; immune protection; spike specific IgG; virus-like particle (VLP) immunization.

Publication types

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

MeSH terms

Antibodies, Neutralizing
Antibodies, Viral
Coronavirus Infections*
Humans
Immunization
Middle East Respiratory Syndrome Coronavirus*
Peptide Hydrolases
Peptides

Substances

Antibodies, Neutralizing
Antibodies, Viral
Peptides
Peptide Hydrolases

Grants and funding

This research was supported by scholarships from the Fellowship for Fundamental Academic Fields provided by Seoul National University and the BK21 FOUR education program to JO, by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (Grant No. 2022R1A6A3A13073817) to UP, grants from the NRF funded by the Ministry of Science and ICT (Grant No. 2017R1A2B2008507 and 2021M3A9I2080493 to YSC and Grant No. 2021M3A9I2080490 to N-HC), and from the Creative-Pioneering Researchers Program funded by Seoul National University and SNUH Research fund (Grant No. 320200270) to YC.