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Sci Rep ; 13(1): 18902, 2023 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-37919366

RESUMO

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 LD78ß/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.


Assuntos
COVID-19 , Vacinas Anticâncer , Vacinas de DNA , Animais , Humanos , Camundongos , Vacinas contra COVID-19 , SARS-CoV-2 , Pandemias , COVID-19/prevenção & controle , Linfócitos T , Células Apresentadoras de Antígenos , Anticorpos Amplamente Neutralizantes , DNA , Imunoglobulina G , Anticorpos Neutralizantes , Anticorpos Antivirais
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