Optimization of antigen dose for a receptor-binding domain-based subunit vaccine against MERS coronavirus

Hum Vaccin Immunother. 2015;11(5):1244-50. doi: 10.1080/21645515.2015.1021527.


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.

Keywords: MERS; MERS-CoV; antigen doses; receptor-binding domain; subunit vaccines.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Animals
  • Antibodies, Neutralizing / blood
  • Antibodies, Viral / blood
  • Antigens, Viral / administration & dosage
  • Antigens, Viral / genetics
  • Antigens, Viral / immunology
  • Coronavirus Infections / prevention & control*
  • Female
  • Humans
  • Immunity, Cellular
  • Immunity, Humoral
  • Immunoglobulin Fc Fragments / administration & dosage
  • Immunoglobulin Fc Fragments / genetics
  • Immunoglobulin Fc Fragments / immunology
  • Mice, Inbred BALB C
  • Middle East Respiratory Syndrome Coronavirus / immunology*
  • Polysorbates / administration & dosage
  • Recombinant Fusion Proteins / administration & dosage
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology
  • Squalene / administration & dosage
  • Vaccines, Subunit / administration & dosage
  • Vaccines, Subunit / genetics
  • Vaccines, Subunit / immunology
  • Viral Vaccines / administration & dosage*
  • Viral Vaccines / genetics
  • Viral Vaccines / immunology*


  • Adjuvants, Immunologic
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Antigens, Viral
  • Immunoglobulin Fc Fragments
  • MF59 oil emulsion
  • Polysorbates
  • Recombinant Fusion Proteins
  • Vaccines, Subunit
  • Viral Vaccines
  • Squalene