tetano
Editor, Senior Moderator
JCI Insight
. 2021 Apr 22;146082.
doi: 10.1172/jci.insight.146082. Online ahead of print.
Intradermal delivery of a synthetic DNA vaccine protects macaques from Middle East respiratory syndrome coronavirus
Ami Patel[SUP] 1 [/SUP], Emma L Reuschel[SUP] 1 [/SUP], Ziyang Xu[SUP] 1 [/SUP], Faraz I Zaidi[SUP] 1 [/SUP], Kevin Y Kim[SUP] 1 [/SUP], Dana P Scott[SUP] 2 [/SUP], Janess Mendoza[SUP] 3 [/SUP], Stephanie Ramos[SUP] 3 [/SUP], Regina Stoltz[SUP] 1 [/SUP], Friederike Feldmann[SUP] 2 [/SUP], Atsushi Okumura[SUP] 4 [/SUP], Kimberly Meade-White[SUP] 4 [/SUP], Elaine Haddock[SUP] 4 [/SUP], Tina Thomas[SUP] 5 [/SUP], Rebecca Rosenke[SUP] 5 [/SUP], Jamie Lovaglio[SUP] 5 [/SUP], Patrick W Hanley[SUP] 5 [/SUP], Greg Saturday[SUP] 5 [/SUP], Kar Muthumani[SUP] 1 [/SUP], Heinz Feldmann[SUP] 4 [/SUP], Laurent M Humeau[SUP] 3 [/SUP], Kate E Broderick[SUP] 3 [/SUP], David B Weiner[SUP] 1 [/SUP]
Affiliations
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 (ID) and intramuscular (IM) two-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 to controls. ID 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.
Keywords: Adaptive immunity; Infectious disease; Vaccines.
. 2021 Apr 22;146082.
doi: 10.1172/jci.insight.146082. Online ahead of print.
Intradermal delivery of a synthetic DNA vaccine protects macaques from Middle East respiratory syndrome coronavirus
Ami Patel[SUP] 1 [/SUP], Emma L Reuschel[SUP] 1 [/SUP], Ziyang Xu[SUP] 1 [/SUP], Faraz I Zaidi[SUP] 1 [/SUP], Kevin Y Kim[SUP] 1 [/SUP], Dana P Scott[SUP] 2 [/SUP], Janess Mendoza[SUP] 3 [/SUP], Stephanie Ramos[SUP] 3 [/SUP], Regina Stoltz[SUP] 1 [/SUP], Friederike Feldmann[SUP] 2 [/SUP], Atsushi Okumura[SUP] 4 [/SUP], Kimberly Meade-White[SUP] 4 [/SUP], Elaine Haddock[SUP] 4 [/SUP], Tina Thomas[SUP] 5 [/SUP], Rebecca Rosenke[SUP] 5 [/SUP], Jamie Lovaglio[SUP] 5 [/SUP], Patrick W Hanley[SUP] 5 [/SUP], Greg Saturday[SUP] 5 [/SUP], Kar Muthumani[SUP] 1 [/SUP], Heinz Feldmann[SUP] 4 [/SUP], Laurent M Humeau[SUP] 3 [/SUP], Kate E Broderick[SUP] 3 [/SUP], David B Weiner[SUP] 1 [/SUP]
Affiliations
- PMID: 33886507
- DOI: 10.1172/jci.insight.146082
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 (ID) and intramuscular (IM) two-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 to controls. ID 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.
Keywords: Adaptive immunity; Infectious disease; Vaccines.