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Intradermal delivery of a synthetic DNA vaccine protects macaques from Middle East respiratory syndrome coronavirus
Ami Patel, Emma L. Reuschel, Ziyang Xu, Faraz I. Zaidi, Kevin Y. Kim, Dana P. Scott, Janess Mendoza, Stephanie Ramos, Regina Stoltz, Friederike Feldmann, Atsushi Okumura, Kimberly Meade-White, Elaine Haddock, Tina Thomas, Rebecca Rosenke, Jamie Lovaglio, Patrick W. Hanley, Greg Saturday, Kar Muthumani, Heinz Feldmann, Laurent M. Humeau, Kate E. Broderick, David B. Weiner
Ami Patel, Emma L. Reuschel, Ziyang Xu, Faraz I. Zaidi, Kevin Y. Kim, Dana P. Scott, Janess Mendoza, Stephanie Ramos, Regina Stoltz, Friederike Feldmann, Atsushi Okumura, Kimberly Meade-White, Elaine Haddock, Tina Thomas, Rebecca Rosenke, Jamie Lovaglio, Patrick W. Hanley, Greg Saturday, Kar Muthumani, Heinz Feldmann, Laurent M. Humeau, Kate E. Broderick, David B. Weiner
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Research Article Infectious disease Vaccines

Intradermal delivery of a synthetic DNA vaccine protects macaques from Middle East respiratory syndrome coronavirus

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Abstract

Emerging coronaviruses from zoonotic reservoirs, including severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have been associated with human-to-human transmission and significant morbidity and mortality. Here, we study both intradermal and intramuscular 2-dose delivery regimens of an advanced synthetic DNA vaccine candidate encoding a full-length MERS-CoV spike (S) protein, which induced potent binding and neutralizing antibodies as well as cellular immune responses in rhesus macaques. In a MERS-CoV challenge, all immunized rhesus macaques exhibited reduced clinical symptoms, lowered viral lung load, and decreased severity of pathological signs of disease compared with controls. Intradermal vaccination was dose sparing and more effective in this model at protecting animals from disease. The data support the further study of this vaccine for preventing MERS-CoV infection and transmission, including investigation of such vaccines and simplified delivery routes against emerging coronaviruses.

Authors

Ami Patel, Emma L. Reuschel, Ziyang Xu, Faraz I. Zaidi, Kevin Y. Kim, Dana P. Scott, Janess Mendoza, Stephanie Ramos, Regina Stoltz, Friederike Feldmann, Atsushi Okumura, Kimberly Meade-White, Elaine Haddock, Tina Thomas, Rebecca Rosenke, Jamie Lovaglio, Patrick W. Hanley, Greg Saturday, Kar Muthumani, Heinz Feldmann, Laurent M. Humeau, Kate E. Broderick, David B. Weiner

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Figure 1

Study timeline and immune responses induced by MERS DNA vaccine.

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Study timeline and immune responses induced by MERS DNA vaccine.
(A) Imm...
(A) Immunization and blood collection timeline. Rhesus macaques (n = 6) were immunized i.m. with 1 mg or i.d. with 2 mg (i.d.-high), 1 mg (i.d.-mid), or 0.2 mg (i.d.-low) of MERS DNA vaccine at the indicated time points. Control animals were not vaccinated. Blood was collected at the indicated time points for immune analysis. (B) Vaccine-induced antigen-specific IFN-γ ELISPOT responses represented by peptide pool. PBMCs from each animal at each time point were stimulated with peptide pools covering the MERS spike protein, and numbers of cells secreting IFN-γ were counted. Group average spot-forming units (SFU) per million cells are presented for each peptide pool. Error bars represent SEM. (C) Protein stimulated antigen-specific IFN-γ ELISPOT responses. PBMCs from each animal at each time point were stimulated with recombinant full-length MERS S protein, and numbers of cells secreting IFN-γ were counted. Individual values are shown by the symbols with the group average indicated by the bar. Error bars represent mean ± SEM. Animals represented with closed symbols were challenged with MERS-CoV 4 weeks after final immunization. Open symbols depict the responses for animals that were not selected for challenge. (D) Vaccine-induced MERS spike–specific endpoint binding titers. Sera from each animal at each time point were evaluated for their ability to bind to full-length MERS S, S1, S2, and RBD proteins. Endpoint titers for individual animals are shown with the geometric mean and 95% confidence interval indicated by the bars. Error bars represent mean ± SEM. Animals represented with closed symbols were challenged with MERS-CoV 4 weeks after final immunization Open symbols depict responses for animals that were not selected for challenge. (E) Vaccine-induced neutralizing antibody titers in challenged animals (n = 4/vaccinated groups, n = 6/naive). Sera were evaluated for their ability to neutralize MERS-CoV. Reciprocal neutralizing antibody (nAb) titers are shown, with boxed indicating 25th percentile, median, and 75th percentile, and whiskers showing the minimum and maximum values.

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