title: Optimization of antigen dose for a receptor-binding domain-based subunit vaccine against MERS coronavirus.
abstract: Middle East respiratory syndrome (MERS) is an emerging infectious disease caused by MERS coronavirus (MERS-CoV). The continuous increase of MERS cases has posed a serious threat to public health worldwide, calling for development of safe and effective MERS vaccines. We have previously shown that a recombinant protein containing residues 377-588 of MERS-CoV receptor-binding domain (RBD) fused with human Fc (S377-588-Fc) induced highly potent anti-MERS-CoV neutralizing antibodies in the presence of MF59 adjuvant. Here we optimized the doses of S377-588-Fc using MF59 as an adjuvant in order to elicit strong immune responses with minimal amount of antigen. Our results showed that S377-588-Fc at 1 μg was able to induce in the immunized mice potent humoral and cellular immune responses. Particularly, S377-588-Fc at 1 μg elicited strong neutralizing antibody responses against both pseudotyped and live MERS-CoV similar to those induced at 5 and 20 μg, respectively. These results suggest that this RBD-based subunit MERS vaccine candidate at the dose as low as one μg is sufficiently potent to induce strong humoral and cellular immune responses, including neutralizing antibodies, against MERS-CoV infection, thus providing guidance for determining the optimal dosage of RBD-based MERS vaccines in the future clinical trials and for applying the dose-sparing strategy in other subunit vaccine trials.
authors: a Xiang-Ya Medical College; Central South University; , Changsha , China.
authors: Jian
authors: J
authors: Tang
authors: Naru
authors: N
authors: Zhang
authors: Xinrong
authors: X
authors: Tao
authors: Guangyu
authors: G
authors: Zhao
authors: Yan
authors: Y
authors: Guo
authors: Chien-Te K
authors: CT
authors: Tseng
authors: Shibo
authors: S
authors: Jiang
authors: Lanying
authors: L
authors: Du
authors: Yusen
authors: Y
authors: Zhou
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D018352:Coronavirus Infections / Q000517:prevention & control*; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007141:Immunoglobulin Fc Fragments / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D008807:Mice, Inbred BALB C; D065207:Middle East Respiratory Syndrome Coronavirus / Q000276:immunology*; D011136:Polysorbates / Q000008:administration & dosage; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D013185:Squalene / Q000008:administration & dosage; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000956:Antigens, Viral; D007141:Immunoglobulin Fc Fragments; C089950:MF59 oil emulsion; D011136:Polysorbates; D011993:Recombinant Fusion Proteins; D022223:Vaccines, Subunit; D014765:Viral Vaccines; D013185:Squalene
keywords: MERS; MERS-CoV; antigen doses; receptor-binding domain; subunit vaccines