Subunit vaccines with a saponin-based adjuvant boost humoral and cellular immunity to MERS coronavirus

• Published in: Vaccine Vol. 41; no. 21; pp. 3337 - 3346
• Main Authors: Chang, Chi-Chieh, Algaissi, Abdullah, Lai, Chia-Chun, Chang, Chun-Kai, Lin, Jr-Shiuan, Wang, Yi-Shiang, Chang, Bo-Hau, Chang, Yu-Chiuan, Chen, Wei-Ting, Fan, Yong-Qing, Peng, Bi‐Hung, Chao, Chih-Yu, Tzeng, Shiou-Ru, Liang, Pi-Hui, Sung, Wang-Chou, Hu, Alan Yung-Chih, Chang, Shin C., Chang, Ming-Fu
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 16.05.2023; Elsevier Limited; Published by Elsevier Ltd
• Subjects: Adjuvant effects; Adjuvants; Adjuvants, Immunologic; Allergy and Immunology; Amino acids; Animals; Antibodies; Antibodies, Neutralizing; Antibodies, Viral; Cell-mediated immunity; Cellular immunity; Clinical trials; Coronavirus Infections; Coronaviruses; Dipeptidyl Peptidase 4; Disease transmission; genetically modified organisms; Humans; Humoral immunity; Immunity; Immunity, Cellular; Immunization; Immunogenicity; Immunological memory; Infections; Lymphocytes; Lymphocytes T; Memory cells; MERS-CoV neutralization; Mice; Mice, Transgenic; Middle East respiratory syndrome; Middle East Respiratory Syndrome Coronavirus; mortality; Penicillin; Protein expression; Proteins; Public health; Recombinant Proteins; Respiratory diseases; Saponins; Severe acute respiratory syndrome coronavirus 2; Spike Glycoprotein, Coronavirus; Spike protein; Subunit vaccine development; subunit vaccines; T-lymphocytes; Transgenic mice; vaccination; Vaccines; Vaccines, Subunit; Viral Vaccines; Viruses; MERS-CoV neutralization; Cellular immunity; Subunit vaccine development; Adjuvant effects
• DOI: 10.1016/j.vaccine.2023.04.006
• ISSN: 0264-410X; 1873-2518

•MERS-CoV S1-Fd induces high levels of neutralizing activity as well as S1-specific IgG and isotypes.•MERS-CoV S1-Fd protects against MERS-CoV challenge and reduces viral loads in lung.•QS-21 but not AddaVax adjuvanted MERS-CoV S1-Fd activates long-term cellular immunity. Middle East respiratory syndrome coronavirus (MERS-CoV) outbreaks have constituted a public health issue with drastic mortality higher than 34%, necessitating the development of an effective vaccine. During MERS-CoV infection, the trimeric spike protein on the viral envelope is primarily responsible for attachment to host cellular receptor, dipeptidyl peptidase 4 (DPP4). With the goal of generating a protein-based prophylactic, we designed a subunit vaccine comprising the recombinant S1 protein with a trimerization motif (S1-Fd) and examined its immunogenicity and protective immune responses in combination with various adjuvants. We found that sera from immunized wild-type and human DPP4 transgenic mice contained S1-specific antibodies that can neutralize MERS-CoV infection in susceptible cells. Vaccination with S1-Fd protein in combination with a saponin-based QS-21 adjuvant provided long-term humoral as well as cellular immunity in mice. Our findings highlight the significance of the trimeric S1 protein in the development of MERS-CoV vaccines and offer a suitable adjuvant, QS-21, to induce robust and prolonged memory T cell response.