Heterologous prime-boost vaccination with adenoviral vector and protein nanoparticles induces both Th1 and Th2 responses against Middle East respiratory syndrome coronavirus

Vaccine. 2018 Jun 7;36(24):3468-3476. doi: 10.1016/j.vaccine.2018.04.082. Epub 2018 May 5.


The Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic and zoonotic virus with a fatality rate in humans of over 35%. Although several vaccine candidates have been developed, there is still no clinically available vaccine for MERS-CoV. In this study, we developed two types of MERS-CoV vaccines: a recombinant adenovirus serotype 5 encoding the MERS-CoV spike gene (Ad5/MERS) and spike protein nanoparticles formulated with aluminum (alum) adjuvant. Next, we tested a heterologous prime-boost vaccine strategy, which compared priming with Ad5/MERS and boosting with spike protein nanoparticles and vice versa, with homologous prime-boost vaccination comprising priming and boosting with either spike protein nanoparticles or Ad5/MERS. Although both types of vaccine could induce specific immunoglobulin G against MERS-CoV, neutralizing antibodies against MERS-CoV were induced only by heterologous prime-boost immunization and homologous immunization with spike protein nanoparticles. Interestingly, Th1 cell activation was induced by immunization schedules including Ad5/MERS, but not by those including only spike protein nanoparticles. Heterologous prime-boost vaccination regimens including Ad5/MERS elicited simultaneous Th1 and Th2 responses, but homologous prime-boost regimens did not. Thus, heterologous prime-boost may induce longer-lasting immune responses against MERS-CoV because of an appropriate balance of Th1/Th2 responses. However, both heterologous prime-boost and homologous spike protein nanoparticles vaccinations could provide protection from MERS-CoV challenge in mice. Our results demonstrate that heterologous immunization by priming with Ad5/MERS and boosting with spike protein nanoparticles could be an efficient prophylactic strategy against MERS-CoV infection.

Keywords: Adenovirus 5; Heterologous prime–boost; MERS-CoV; Th1; Th2; Vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviruses, Human / genetics
  • Adenoviruses, Human / immunology*
  • Adjuvants, Immunologic / administration & dosage
  • Alum Compounds / administration & dosage
  • Animals
  • Antibodies, Neutralizing / biosynthesis
  • Antibodies, Viral / biosynthesis
  • Coronavirus Infections / immunology
  • Coronavirus Infections / prevention & control*
  • Coronavirus Infections / virology
  • Female
  • Humans
  • Immunization Schedule
  • Immunization, Secondary / methods*
  • Immunogenicity, Vaccine
  • Immunoglobulin G / biosynthesis
  • Lymphocyte Activation / drug effects*
  • Mice
  • Mice, Inbred BALB C
  • Middle East Respiratory Syndrome Coronavirus / drug effects*
  • Middle East Respiratory Syndrome Coronavirus / genetics
  • Middle East Respiratory Syndrome Coronavirus / immunology
  • Nanoparticles / administration & dosage
  • Nanoparticles / chemistry
  • Spike Glycoprotein, Coronavirus / administration & dosage
  • Spike Glycoprotein, Coronavirus / genetics
  • Spike Glycoprotein, Coronavirus / immunology*
  • Th1 Cells / drug effects
  • Th1 Cells / immunology
  • Th1 Cells / virology
  • Th2 Cells / drug effects
  • Th2 Cells / immunology
  • Th2 Cells / virology
  • Viral Vaccines / administration & dosage
  • Viral Vaccines / genetics
  • Viral Vaccines / immunology


  • Adjuvants, Immunologic
  • Alum Compounds
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Immunoglobulin G
  • Spike Glycoprotein, Coronavirus
  • Viral Vaccines