tetano
Editor, Senior Moderator
Sci Rep
. 2023 Nov 2;13(1):18902.
doi: 10.1038/s41598-023-46223-8. A novel SARS-CoV-2 Beta RBD DNA vaccine directly targeted to antigen-presenting cells induces strong humoral and T cell responses
Katarzyna Kuczkowska[SUP] #[/SUP][SUP] 1 [/SUP], Louise Bjerkan[SUP] #[/SUP][SUP] 2 [/SUP], Elisabeth Stubsrud[SUP] 2 [/SUP], Hannah Cuthbertson Husbyn[SUP] 2 [/SUP], Stalin Chellappa[SUP] 2 3 [/SUP], Anette Hauge[SUP] 2 [/SUP], Renate Skarshaug[SUP] 2 [/SUP], Maria Lyngaas Torgersen[SUP] 2 [/SUP], Joel Benjamin Heim[SUP] 2 [/SUP], Marthe Jøntvedt Jørgensen[SUP] 2 [/SUP], Christian Winther Wold[SUP] 2 [/SUP], Mariane Høgsbjerg Schleimann[SUP] 4 [/SUP], Martin Tolstrup[SUP] 4 [/SUP], Stine Granum[SUP] 2 [/SUP], Agnete Brunsvik Fredriksen[SUP] 2 [/SUP], Mikkel Wandahl Pedersen[SUP] 2 [/SUP], Gunnstein Norheim[SUP] 2 [/SUP]
Affiliations
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 C[SUB]H[/SUB]3 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 Nov 2;13(1):18902.
doi: 10.1038/s41598-023-46223-8. A novel SARS-CoV-2 Beta RBD DNA vaccine directly targeted to antigen-presenting cells induces strong humoral and T cell responses
Katarzyna Kuczkowska[SUP] #[/SUP][SUP] 1 [/SUP], Louise Bjerkan[SUP] #[/SUP][SUP] 2 [/SUP], Elisabeth Stubsrud[SUP] 2 [/SUP], Hannah Cuthbertson Husbyn[SUP] 2 [/SUP], Stalin Chellappa[SUP] 2 3 [/SUP], Anette Hauge[SUP] 2 [/SUP], Renate Skarshaug[SUP] 2 [/SUP], Maria Lyngaas Torgersen[SUP] 2 [/SUP], Joel Benjamin Heim[SUP] 2 [/SUP], Marthe Jøntvedt Jørgensen[SUP] 2 [/SUP], Christian Winther Wold[SUP] 2 [/SUP], Mariane Høgsbjerg Schleimann[SUP] 4 [/SUP], Martin Tolstrup[SUP] 4 [/SUP], Stine Granum[SUP] 2 [/SUP], Agnete Brunsvik Fredriksen[SUP] 2 [/SUP], Mikkel Wandahl Pedersen[SUP] 2 [/SUP], Gunnstein Norheim[SUP] 2 [/SUP]
Affiliations
- PMID: 37919366
- DOI: 10.1038/s41598-023-46223-8
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 C[SUB]H[/SUB]3 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.