Immunogenicity of Candidate MERS-CoV DNA Vaccines Based on the Spike Protein

Sawsan S Al-Amri,Anwar M Hashem,Rowa Y Alhabbab,Mohammad A Sanki,Ayman T Abbas,Abrar Alghamdi,Loai A Siddiq,Muhanna K Al-Muhanna,Esam I Azhar,Xuguang Li

doi:10.1038/srep44875

Abstract

MERS-coronavirus is a novel zoonotic pathogen which spread rapidly to >25 countries since 2012. Its apparent endemicity and the wide spread of its reservoir host (dromedary camels) in the Arabian Peninsula highlight the ongoing public health threat of this virus. Therefore, development of effective prophylactic vaccine needs to be urgently explored given that there are no approved prophylactics or therapeutics for humans or animals to date. Different vaccine candidates have been investigated but serious safety concerns remain over protein or full-length spike (S) protein-based vaccines. Here, we investigated the immunogenicity of naked DNA vaccines expressing different fragments of MERS-CoV S protein in mice. We found that plasmids expressing full-length (pS) or S1-subunit (pS1) could induce significant levels of S1-specific antibodies (Abs) but with distinct IgG isotype patterns. Specifically, pS1 immunization elicited a balanced Th1/Th2 response and generally higher levels of all IgG isotypes compared to pS vaccination. Interestingly, only mice immunized with pS1 demonstrated significant S1-specific cellular immune response. Importantly, both constructs induced cross-neutralizing Abs against multiple strains of human and camel origins. These results indicate that vaccines expressing S1-subunit of the MERS-CoV S protein could represent a potential vaccine candidate without the possible safety concerns associated with full-length protein-based vaccines.

Highlights

Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging zoonotic pathogen recovered first from a fatal human case in Saudi Arabia in 20121 and continued to infect almost 1800 people in over 25 countries
PS1 elicited significantly higher levels of S1-specific total IgG compared to plasmids expressing full-length (pS) immunized mice
It is of note that DNA construct expressing truncated S protein without the cytoplasmic domain failed to induce detectable Abs in initial pilot studies; it was not tested further

Summary

Introduction

Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging zoonotic pathogen recovered first from a fatal human case in Saudi Arabia in 20121 and continued to infect almost 1800 people in over 25 countries. The ability of more than 60% of the infected patients to recover, clear the virus and develop immunity suggest that a vaccine based on the viral components such as the spike (S) glycoprotein could be a suitable vaccine candidate This is further supported by the isolation of several human neutralizing antibodies (nAbs) against the MERS-CoV S protein and their ability to neutralize and block viral entry and/or cell-cell spread at very low concentrations, and sometimes to confer prophylactic and therapeutic protection in animal models[21,22,23,24,25,26,27]. We determined the immunogenicity and potential protective effects of MERS-CoV naked DNA vaccines expressing different length of S protein

Methods

Results

Conclusion