Trimeric protein vaccine based on Beta variant elicits robust immune response against BA.4/5-included SARS-CoV-2 Omicron variants

The current Coronavirus Disease 2019 (COVID-19) pandemic, induced by newly emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variants, posed great threats to global public health security. There is an urgent need to design effective next‑generation vaccines against Omicron lineages. Here, we investigated the immunogenic capacity of the vaccine candidate based on the receptor binding domain (RBD). An RBD(β)-HR self-assembled trimer vaccine including RBD of Beta variant (containing K417, E484 and N501) and heptad repeat (HR) subunits was developed using an insect cell expression platform. Sera obtained from immunized mice effectively blocked RBD-human angiotensin-converting enzyme 2 (hACE2) binding for different viral variants, showing robust inhibitory activity. In addition, RBD(β)-HR/trimer vaccine durably exhibited high titers of specific binding antibodies and high levels of cross-protective neutralizing antibodies against newly emerging Omicron lineages, as well as other major variants including Alpha, Beta, and Delta. Consistently, the vaccine also promoted a broad and potent cellular immune response involving the participation of T follicular helper (Tfh) cells, germinal center (GC) B cells, activated T cells, effector memory T cells, and central memory T cells, which are critical facets of protective immunity. These results demonstrated that RBD(β)-HR/trimer vaccine candidates provided an attractive next-generation vaccine strategy against Omicron variants in the global effort to halt the spread of SARS-CoV-2.