Synergistic Immunity and Protection in Mice by Co-Immunization with DNA Vaccines Encoding the Spike Protein and Other Structural Proteins of SARS-CoV-2

Jinni Chen; Baoying Huang; Yao Deng; Wen Wang; Chengcheng Zhai; Di Han; Na Wang; Ying Zhao; Desheng Zhai; Wenjie Tan

doi:10.3390/vaccines11020243

Synergistic Immunity and Protection in Mice by Co-Immunization with DNA Vaccines Encoding the Spike Protein and Other Structural Proteins of SARS-CoV-2

Vaccines (Basel). 2023 Jan 21;11(2):243. doi: 10.3390/vaccines11020243.

Authors

Jinni Chen^{1

2}, Baoying Huang², Yao Deng², Wen Wang², Chengcheng Zhai², Di Han², Na Wang³, Ying Zhao³, Desheng Zhai¹, Wenjie Tan^{1

2}

Affiliations

¹ School of Public Health, Xinxiang Medical University, Xinxiang 453003, China.
² NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, China CDC, Beijing 102206, China.
³ School of Pharmacy, Xinxiang Medical University, Xinxiang 453003, China.

Abstract

The emergence of new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has generated recurring worldwide infection outbreaks. These highly mutated variants reduce the effectiveness of current coronavirus disease 2019 (COVID-19) vaccines, which are designed to target only the spike (S) protein of the original virus. Except for the S of SARS-CoV-2, the immunoprotective potential of other structural proteins (nucleocapsid, N; envelope, E; membrane, M) as vaccine target antigens is still unclear and worthy of investigation. In this study, synthetic DNA vaccines encoding four SARS-CoV-2 structural proteins (pS, pN, pE, and pM) were developed, and mice were immunized with three doses via intramuscular injection and electroporation. Notably, co-immunization with two DNA vaccines that expressed the S and N proteins induced higher neutralizing antibodies and was more effective in reducing the SARS-CoV-2 viral load than the S protein alone in mice. In addition, pS co-immunization with either pN or pE + pM induced a higher S protein-specific cellular immunity after three immunizations and caused milder histopathological changes than pS alone post-challenge. The role of the conserved structural proteins of SARS-CoV-2, including the N/E/M proteins, should be investigated further for their applications in vaccine design, such as mRNA vaccines.

Keywords: COVID-19; DNA vaccine; SARS-CoV-2; co-immunization; spike protein; structural protein.

Grants and funding

This work was supported by grants from the National Natural Science Foundation of China [grant number 82041041 and 8207082400] and the National Key Research and Development Program of China [grant number 2021YFC0863300 and 2022YFC2304100].