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

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.

Control of SARS-CoV-2 infection after Spike DNA or Spike DNA+Protein co-immunization in rhesus macaques

“…An important feature of the SARS-CoV-2 DNA vaccine is its ability to induce robust cellular as well as humoral immune responses (for reviews see [14][15][16][17][18][19][20]). In contrast to mRNA vaccines that induce robust antibody responses and low T cell responses, several clinical trials have shown that IM-as well as intradermal (ID)-delivered DNA vaccines [12,[56][57][58][59][60] are able to induce both humoral and cellular responses and that the latter is a critical component to maintain durable antibody responses exerted by CD4 + T help. Although the underlying mechanism explaining the difference in immunity induced by DNA versus mRNA vaccines is not clear, the ability to induce T cell responses is important not only for antibody development but also as a second line of defense in protection from spreading infection and disease development.…”

“…Our overall experience with DNA vaccines has been that they provide superior cellular immunity in numbers and duration, and the hypothesis to test is that it may be of benefit for the establishment of long-term protective immunity. On the other hand, delivery of DNA via the ID and IM routes in clinical trials has shown the potency of the vaccine platform [12, [56][57][58][59][60]. The combination of DNA with protein delivered simultaneously via the IM route in the same anatomical site further advances the nucleic acid vaccine platform and increases the simultaneous induction of maximal humoral and cellular immune responses.…”

Intradermal Immunization of SARS-CoV-2 Original Strain Trimeric Spike Protein Associated to CpG and AddaS03 Adjuvants, but Not MPL, Provide Strong Humoral and Cellular Response in Mice

“…Nonetheless, many vaccine candidates against SARS-CoV-2 using the intradermal route (i.d.) have shown promising results, either on laboratory tests on different animal models [5][6][7][8], or in development with clinical trials [9,10]. The i.d.…”