A novel circular Delta-XBB.1.5 RBD dimeric protein subunit vaccine
mediated by split intein elicits an immune response and protection
against multiple SARS-CoV-2 variants in mice
Abstract
SARS-CoV-2 continues to mutate, leading to breakthrough infections. The
development of new vaccine strategies to combat variant strains is
crucial. Protein cyclization can enhance thermal stability and may
improve immunogenicity. Here, we designed a cyclic tandem dimeric
receptor-binding domain protein (cirRBD2) using the split intein
Cth-Ter. Cyclization does not affect the antigen epitopes of the RBD but
results in better thermal stability than that of its linear counterpart
(linRBD2). Compared with those immunized with linRBD2, mice immunized
with two doses of 5 μg of cirRBD2 produced significantly greater levels
of broad-spectrum neutralizing antibodies than those immunized with
linRBD2 and generated a considerable cellular immune response. In the
VEEV-VRP-hACE2-transduced mouse model, two doses of 5 μg of cirRBD2
provided protection against infection with BA.5, XBB.1.9, and partial
against EG.5 which has more mutations. This study developed a novel
circular RBD dimer subunit vaccine for SARS-CoV-2 that exhibits
broad-spectrum neutralizing activity against various variants. A similar
strategy can be applied to develop vaccines for other pathogens,
especially for thermally stable vaccines.