SARS-CoV-2 spike RBD and nucleocapsid encoding DNA vaccine elicits T cell and neutralising antibody responses that cross react with variants

Brentville, VA ORCID: 0000-0003-2000-5629, Vankemmelbeke, M ORCID: 0000-0002-7239-1640, Metheringham, RL, Symonds, P, Cook, KW, Urbanowicz, RA ORCID: 0000-0002-2461-4993, Tsoleridis, T, Coleman, CM, Chang, K-C, Skinner, A
et al (show 14 more authors) (2021) SARS-CoV-2 spike RBD and nucleocapsid encoding DNA vaccine elicits T cell and neutralising antibody responses that cross react with variants. Unknown. 2021.06.18.448932-.

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<jats:title>Abstract</jats:title><jats:p>Although the efficacy of vaccines targeting SARS-CoV-2 is apparent now that the approved mRNA and adenovirus vector vaccines are in widespread use, the longevity of the protective immune response and its efficacy against emerging variants remains to be determined. We have therefore designed a DNA vaccine encoding both the SARS-CoV-2 spike receptorbinding domain (‘RBD’) and nucleocapsid proteins, the latter of which is highly conserved amongst beta coronaviruses. The vaccine elicits strong pro-inflammatory CD4<jats:sup>+</jats:sup>Th1 and CD8<jats:sup>+</jats:sup>T-cell responses to both proteins in mice and rats, with responses being significantly enhanced by fusing the nucleocapsid sequence to a modified Fc domain. We have shown that the vaccine also stimulates high titre antibody responses to RBD in mice that efficiently neutralise in pseudotype and live virus neutralisation assays and show cross reactivity with spike proteins from the variants B.1.1.7 (Alpha), B.1.351 (Beta) and B.1.617.2 (Delta). The vaccine also showed good protection in a viral challenge model in ACE2 receptor transgenic mice. This DNA platform can be easily adapted to target variant proteins and we show that a vaccine variant encoding the Beta variant sequence stimulates cross-reactive humoral and T cell responses. These data support the translation of this DNA vaccine platform into the clinic, thereby offering a particular advantage for rapidly targeting emerging SARS-CoV-2 variants.</jats:p>

Item Type: Article
Uncontrolled Keywords: Infectious Diseases, Genetics, Vaccine Related, Biodefense, Pneumonia, Immunization, Emerging Infectious Diseases, Prevention, Lung, Pneumonia & Influenza, Biotechnology, 2 Aetiology, 2.1 Biological and endogenous factors, 3 Prevention of disease and conditions, and promotion of well-being, 3.4 Vaccines, Infection, 3 Good Health and Well Being
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences
Depositing User: Symplectic Admin
Date Deposited: 10 Sep 2021 13:07
Last Modified: 15 Mar 2024 17:57
DOI: 10.1101/2021.06.18.448932
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