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. 2015 Aug;89(16):8651-6.
doi: 10.1128/JVI.00614-15. Epub 2015 May 27.

Protective Efficacy of Recombinant Modified Vaccinia Virus Ankara Delivering Middle East Respiratory Syndrome Coronavirus Spike Glycoprotein

Asisa Volz  1 , Alexandra Kupke  2 , Fei Song  1 , Sylvia Jany  1 , Robert Fux  1 , Hosam Shams-Eldin  2 , Jörg Schmidt  2 , Christin Becker  3 , Markus Eickmann  2 , Stephan Becker  2 , Gerd Sutter  4
Affiliations

Protective Efficacy of Recombinant Modified Vaccinia Virus Ankara Delivering Middle East Respiratory Syndrome Coronavirus Spike Glycoprotein

Asisa Volz et al. J Virol. 2015 Aug.

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe respiratory disease in humans. We tested a recombinant modified vaccinia virus Ankara (MVA) vaccine expressing full-length MERS-CoV spike (S) glycoprotein by immunizing BALB/c mice with either intramuscular or subcutaneous regimens. In all cases, MVA-MERS-S induced MERS-CoV-specific CD8(+) T cells and virus-neutralizing antibodies. Vaccinated mice were protected against MERS-CoV challenge infection after transduction with the human dipeptidyl peptidase 4 receptor. This MERS-CoV infection model demonstrates the safety and efficacy of the candidate vaccine.

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Figures

FIG 1
FIG 1
Antibody response induced by MVA-MERS-S vaccination. Groups of BALB/c mice (n = 5) were immunized s.c. (A) or i.m. (B) with 106, 107, or 108 PFU of MVA-MERS-S, 108 PFU of nonrecombinant MVA (WT), or phosphate-buffered saline (Mock). To monitor antibody responses, we analyzed the MERS-CoV-neutralizing capacity of mouse serum samples taken at days 21 and 40. Serum antibodies against MERS-CoV were measured by virus neutralization assay (VNT) after primary vaccination and after prime-boost vaccination. Shown are the mean serum antibody titers (log2) of individual animals. The statistical evaluation was performed with GraphPad Prism for Windows (GraphPad Software, La Jolla, CA). Statistical significance of differences between groups is indicated as follows: *, P < 0.05; **, P < 0.01; ns, no statistically significant difference.
FIG 2
FIG 2
Virus-specific CD8+ T-cell responses induced by MVA-MERS-S. BALB/c mice were immunized by single-shot and prime-boost vaccinations with 106, 107, or 108 PFU of MVA-MERS-S vaccine via the s.c. (A) or i.m. (B) route. Animals inoculated with nonrecombinant MVA (WT) or phosphate-buffered saline (Mock) were used as controls. Splenocytes were prepared at 8 days after prime or prime-boost vaccination, and S291-specific IFN-γ-producing CD8+ T cells (IFN-γ spot-forming cells) were measured by ELISPOT assay. (C) Virus-specific memory CD8+ T-cell responses induced by MVA-MERS-S. Spleen cells were harvested at 56 days after prime or prime-boost vaccination. MERS S-specific CD8+ T cells were stimulated with peptide S291. Peptide SPYAAGYDL (F2L) served for comparative analysis of MVA-specific CD8+ T cells (30). MERS-CoV S-specific T cells were quantified by IFN-γ ELISPOT assay (A.EL.VIS, Hannover, Germany). Statistical evaluation by t test was performed with GraphPad Prism for Windows (GraphPad Software, La Jolla, CA). For statistically significant differences between results, the following convention is used: *, P < 0.05.
FIG 3
FIG 3
Protective capacity of MVA-MERS-S immunization against challenge with MERS-CoV in human DPP4-transduced BALB/c mice. BALB/c mice were infected with 7 × 104 TICD50 of MERS-CoV 45 days after immunization with 106, 107, or 108 PFU of MVA-MERS. MERS-CoV RNA loads in lung tissues were determined by quantitative real-time reverse transcription-PCR (31). Numbers of viral genome copies per nanogram of RNA are shown for groups of animals (n, number of animals per group) immunized by the s.c. route with 106 (n = 5), 107 (n = 2), or 108 (n = 2) PFU of MVA-MERS-S (MVA-S), nonrecombinant MVA (WT) (n = 1), or phosphate-buffered saline (Mock) (n = 4) (A) or vaccinated by the i.m. route with 106 (n = 5), 107 (n = 5), or 108 (n = 5) PFU of MVA-MERS-S (MVA-S), nonrecombinant MVA (WT) (n = 3), or phosphate-buffered saline (Mock) (n = 4) (B). The statistical evaluation was performed with GraphPad Prism for Windows (GraphPad Software, La Jolla, CA). Statistical significance of differences between groups is indicated as follows: *, P < 0.05; **, P < 0.01; ns, no statistically significant difference.
FIG 4
FIG 4
Histopathological and immunohistochemical examination of MVA-MERS-S-immunized (B, D, F, H), nonrecombinant MVA-vaccinated (A, C, E), and mock-vaccinated (G) mice that had been transduced with a nonreplicating adenoviral vector encoding human DPP4 and mCherry. Mice were infected with MERS-CoV (A to H) or mock infected and monitored for inflammation caused by adenoviral vector transduction (I, J). Lungs were collected 4 days postinfection (A to H) or 5 days after transduction with the control adenoviral vector (I, J); fixed tissue was routinely embedded in paraffin and stained with hematoxylin and eosin (H&E). For immunohistochemical detection of MERS-CoV, a rabbit polyclonal antibody against the spike protein S1 (Sino Biological Inc., catalog no. 100208-RP) was used. Since all of the antibodies tested against human DPP4 showed partial cross-reactivity with murine DPP4, a mouse monoclonal antibody against mCherry (Abcam catalog no. ab125096) was used to monitor adenoviral transduction. Shown are the results of H&E staining (A to D, I) and immunohistochemical analyses for MERS-CoV spike protein (E, F, J) and mCherry (G, H). Scale bars: 500 μm (A, B), 200 μm (I, J), and 100 μm (C to H).
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References

    1. Al-Tawfiq JA, Memish ZA. 2014. Middle East respiratory syndrome coronavirus: epidemiology and disease control measures. Infect Drug Resist 7:281–287. - PMC - PubMed
    1. Al-Tawfiq JA, Memish ZA. 2014. Middle East respiratory syndrome coronavirus: transmission and phylogenetic evolution. Trends Microbiol 22:573–579. doi:10.1016/j.tim.2014.08.001. - DOI - PMC - PubMed
    1. Coleman CM, Frieman MB. 2014. Coronaviruses: important emerging human pathogens. J Virol 88:5209–5212. doi:10.1128/JVI.03488-13. - DOI - PMC - PubMed
    1. Raj VS, Mou H, Smits SL, Dekkers DHW, Muller MA, Dijkman R, Muth D, Demmers JAA, Zaki A, Fouchier RAM, Thiel V, Drosten C, Rottier PJM, Osterhaus ADME, Bosch BJ, Haagmans BL. 2013. Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC. Nature 495:251–254. doi:10.1038/nature12005. - DOI - PMC - PubMed
    1. Agrawal AS, Garron T, Tao X, Peng B-H, Wakamiya M, Chan T-S, Couch RB, Tseng C-TK. 2015. Generation of transgenic mouse model of Middle East respiratory syndrome coronavirus infection and disease. J Virol 89:3659–3670. doi:10.1128/JVI.03427-14. - DOI - PMC - PubMed

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