A novel SARS-CoV-2 Beta RBD DNA vaccine directly targeted to antigen-presenting cells induces strong humoral and T cell responses.
| Title: | A novel SARS-CoV-2 Beta RBD DNA vaccine directly targeted to antigen-presenting cells induces strong humoral and T cell responses. |
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| Authors: | Kuczkowska K; Nykode Therapeutics AS, Oslo Research Park, Gaustadalléen 21, 0349, Oslo, Norway. kkuczkowska@nykode.com.; Bjerkan L; Nykode Therapeutics AS, Oslo Research Park, Gaustadalléen 21, 0349, Oslo, Norway.; Stubsrud E; Nykode Therapeutics AS, Oslo Research Park, Gaustadalléen 21, 0349, Oslo, Norway.; Husbyn HC; Nykode Therapeutics AS, Oslo Research Park, Gaustadalléen 21, 0349, Oslo, Norway.; Chellappa S; Nykode Therapeutics AS, Oslo Research Park, Gaustadalléen 21, 0349, Oslo, Norway.; Veterinærinstituttet, Elizabeth Stephansens Vei 1, 1433, Ås, Norway.; Hauge A; Nykode Therapeutics AS, Oslo Research Park, Gaustadalléen 21, 0349, Oslo, Norway.; Skarshaug R; Nykode Therapeutics AS, Oslo Research Park, Gaustadalléen 21, 0349, Oslo, Norway.; Torgersen ML; Nykode Therapeutics AS, Oslo Research Park, Gaustadalléen 21, 0349, Oslo, Norway.; Heim JB; Nykode Therapeutics AS, Oslo Research Park, Gaustadalléen 21, 0349, Oslo, Norway.; Jørgensen MJ; Nykode Therapeutics AS, Oslo Research Park, Gaustadalléen 21, 0349, Oslo, Norway.; Wold CW; Nykode Therapeutics AS, Oslo Research Park, Gaustadalléen 21, 0349, Oslo, Norway.; Schleimann MH; Department of Clinical Medicine/Infectious Diseases, Aarhus University, Palle Juul-Jensens Boulevard 45, 8200, Aarhus N, Denmark.; Tolstrup M; Department of Clinical Medicine/Infectious Diseases, Aarhus University, Palle Juul-Jensens Boulevard 45, 8200, Aarhus N, Denmark.; Granum S; Nykode Therapeutics AS, Oslo Research Park, Gaustadalléen 21, 0349, Oslo, Norway.; Fredriksen AB; Nykode Therapeutics AS, Oslo Research Park, Gaustadalléen 21, 0349, Oslo, Norway.; Pedersen MW; Nykode Therapeutics AS, Oslo Research Park, Gaustadalléen 21, 0349, Oslo, Norway.; Norheim G; Nykode Therapeutics AS, Oslo Research Park, Gaustadalléen 21, 0349, Oslo, Norway. |
| Source: | Scientific reports [Sci Rep] 2023 Nov 02; Vol. 13 (1), pp. 18902. Date of Electronic Publication: 2023 Nov 02. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: London : Nature Publishing Group, copyright 2011- |
| MeSH Terms: | COVID-19*/prevention & control ; Vaccines, DNA* ; Cancer Vaccines*; Animals ; Humans ; Mice ; COVID-19 Vaccines ; SARS-CoV-2 ; Pandemics ; T-Lymphocytes ; Antigen-Presenting Cells ; Broadly Neutralizing Antibodies ; DNA ; Immunoglobulin G ; Antibodies, Neutralizing ; Antibodies, Viral |
| Abstract: | Throughout the COVID-19 pandemic, several variants of concern (VoC) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have evolved, affecting the efficacy of the approved COVID-19 vaccines. To address the need for vaccines that induce strong and persistent cross-reactive neutralizing antibodies and T cell responses, we developed a prophylactic SARS-CoV-2 vaccine candidate based on our easily and rapidly adaptable plasmid DNA vaccine platform. The vaccine candidate, referred to here as VB2129, encodes a protein homodimer consisting of the receptor binding domain (RBD) from lineage B.1.351 (Beta) of SARS-CoV-2, a VoC with a severe immune profile, linked to a targeting unit (human LD78β/CCL3L1) that binds chemokine receptors on antigen-presenting cells (APCs) and a dimerization unit (derived from the hinge and CH3 exons of human IgG3). Immunogenicity studies in mice demonstrated that the APC-targeted vaccine induced strong antibody responses to both homologous Beta RBD and heterologous RBDs derived from Wuhan, Alpha, Gamma, Delta, and Omicron BA.1 variants, as well as cross-neutralizing antibodies against these VoC. Overall, preclinical data justify the exploration of VB2129 as a potential booster vaccine that induces broader antibody- and T cell-based protection against current and future SARS-CoV-2 VoC.; (© 2023. The Author(s).) |
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| Substance Nomenclature: | 0 (COVID-19 Vaccines); 0 (Vaccines, DNA); 0 (Cancer Vaccines); 0 (Broadly Neutralizing Antibodies); 9007-49-2 (DNA); 0 (Immunoglobulin G); 0 (Antibodies, Neutralizing); 0 (Antibodies, Viral) |
| SCR Organism: | SARS-CoV-2 variants |
| Entry Date(s): | Date Created: 20231103 Date Completed: 20231106 Latest Revision: 20231108 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC10622562 |
| DOI: | 10.1038/s41598-023-46223-8 |
| PMID: | 37919366 |
| Database: | MEDLINE |
Journal Article