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Sci Rep . Modified DNA vaccine confers improved humoral immune response and effective virus protection against SARS-CoV-2 delta variant

tetano

Editor, Senior Moderator
Sci Rep


. 2022 Dec 3;12(1):20923.
doi: 10.1038/s41598-022-24519-5.
Modified DNA vaccine confers improved humoral immune response and effective virus protection against SARS-CoV-2 delta variant


Hiroki Hayashi[SUP] 1 [/SUP], Jiao Sun[SUP] 2 [/SUP], Yuka Yanagida[SUP] 2 [/SUP], Takako Otera[SUP] 2 3 [/SUP], Miwa Sasai[SUP] 4 5 6 [/SUP], Chin Yang Chang[SUP] 7 [/SUP], Jiayu A Tai[SUP] 7 [/SUP], Tomoyuki Nishikawa[SUP] 7 [/SUP], Kunihiko Yamashita[SUP] 7 8 [/SUP], Naoki Sakaguchi[SUP] 8 [/SUP], Shota Yoshida[SUP] 2 9 [/SUP], Satoshi Baba[SUP] 2 9 [/SUP], Munehisa Shimamura[SUP] 2 10 [/SUP], Sachiko Okamoto[SUP] 11 [/SUP], Yasunori Amaishi[SUP] 11 [/SUP], Hideto Chono[SUP] 11 [/SUP], Junichi Mineno[SUP] 11 [/SUP], Hiromi Rakugi[SUP] 9 [/SUP], Ryuichi Morishita[SUP] 12 [/SUP], Masahiro Yamamoto[SUP] 4 5 6 [/SUP], Hironori Nakagami[SUP] 2 6 [/SUP]



Affiliations

Abstract

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to a global pandemic. New technologies have been utilized to develop several types of vaccines to prevent the spread of SARS-CoV-2 infection, including mRNA vaccines. Our group previously developed an effective DNA-based vaccine. However, emerging SARS-CoV-2 variants of concern (VOCs), such as the delta variant, have escaped mutations against vaccine-induced neutralizing antibodies. This suggests that modified vaccines accommodating VOCs need to be developed promptly. Here, we first modified the current DNA vaccine to enhance antigenicity. Compared with the parental DNA vaccine, the modified version (GP∆-DNA vaccine) induced rapid antibody production. Next, we updated the GP∆-DNA vaccine to spike glycoprotein of the delta variant (GP∆-delta DNA vaccine) and compared the efficacy of different injection routes, namely intramuscular injection using a needle and syringe and intradermal injection using a pyro-drive jet injector (PJI). We found that the levels of neutralizing antibodies induced by the intradermal PJI injection were higher than intramuscular injection. Furthermore, the PJI-injected GP∆-delta DNA vaccine effectively protected human angiotensin-converting enzyme 2 (hACE2) knock-in mice from delta-variant infection. These results indicate that the improved DNA vaccine was effective against emerging VOCs and was a potential DNA vaccine platform for future VOCs or global pandemics.
 
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