Elsevier

Vaccine

Volume 36, Issue 24, 7 June 2018, Pages 3468-3476
Vaccine

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

https://doi.org/10.1016/j.vaccine.2018.04.082Get rights and content

Highlights

  • Immunization with MERS spike protein nanoparticles induced only Th2-biased response.

  • Heterologous prime-boost immunization induced both Th1 and Th2-biased responses.

  • Our vaccination strategy showed the protective effect against MERS-CoV.

Abstract

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.

Abbreviations

MERS-CoV
Middle East respiratory syndrome coronavirus
DPP4
Dipeptidyl peptidase 4
RBD
Receptor binding domain
ORF
Open reading frame
Ad5/MERS
Adenovirus 5 expressing MERS-CoV spike protein

Keywords

MERS-CoV
Vaccine
Adenovirus 5
Th1
Th2
Heterologous prime–boost

Cited by (0)

1

These authors contributed equally to this work.

View Abstract