Indeed, the efficacy of the current vaccines targeting conformational RBD epitopes has been challenged by the emergence of VOCs 1, 6, 8, 9, 10, 11, 12. While maintaining fitness, these conformational changes in the S protein are often associated with enhanced virus infectivity and spread in humans 6, 7. The VOCs have conformational changes in the RBD, augmenting their affinity to the Angiotensin Convertase Enzyme-2 (ACE-2) and the ability to escape the action of nAbs 5. However, positive selection of SARS-CoV-2 mutants with amino acid changes in the receptor binding domain (RBD) and adjacent segments from S protein is a frequent event 3, 4 that generates the variants of concern (VOCs). Most if not all COVID-19 vaccines, currently in use, are based on the Spike (S) protein and neutralizing antibodies (nAbs) 1, 2.
Since the end of 2019, over 500 million cases and six million deaths from COVID-19 have been reported worldwide. Hence, vaccine formulations that elicit effector T cells specific for the N and RBD proteins may be used to improve COVID-19 vaccines and potentially circumvent the immune escape by variants of concern. Finally, vaccination with SpiN also protects the K18-ACE-2 mice against infection with Delta and Omicron SARS-CoV-2 isolates. The protection induced by SpiN was ablated by depletion of CD4 + and CD8 + T cells and not transferred by antibodies from vaccinated mice. Importantly, immunization of Syrian hamsters and the human Angiotensin Convertase Enzyme-2-transgenic (K18-ACE-2) mice with Poly ICLC-adjuvanted SpiN promotes robust resistance to the wild type SARS-CoV-2, as indicated by viral load, lung inflammation, clinical outcome and reduction of lethality. In mice, SpiN elicited a strong IFN-γ response by T cells and high levels of antibodies to the inactivated virus, but not detectable neutralizing antibodies (nAbs). Memory CD4 + and CD8 + T cells specific for SpiN could be detected in the blood of both individuals vaccinated with Coronavac SARS-CoV-2 vaccine and COVID-19 convalescent donors. Here, we generate a chimeric protein (SpiN) that comprises the receptor binding domain (RBD) from Spike (S) and the nucleocapsid (N) antigens from SARS-CoV-2. Nature Communications volume 13, Article number: 4831 ( 2022)īoth T cells and B cells have been shown to be generated after infection with SARS-CoV-2 yet protocols or experimental models to study one or the other are less common. Promotion of neutralizing antibody-independent immunity to wild-type and SARS-CoV-2 variants of concern using an RBD-Nucleocapsid fusion protein
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