Subunit vaccine raised against the SARS‐CoV‐2 spike of Delta and Omicron variants

Vaccination has proven effective against SARS‐CoV‐2 infection but vaccines were originally based on the wild type and emerging variants have led to a decrease in protective efficacy. There is an urgent need for broad‐spectrum vaccine protection against emerging variants. A vaccine based on the Delta strain spike protein was created by optimization of vector, codon, and protein structure to produce a subunit immunogen (Delta‐6P‐S) containing six proline mutations, stable pre‐fusion conformation, and with high expression in CHO‐S cells. Immunogenicity and protective efficacy were evaluated in mice and golden hamsters using alum adjuvant. The Delta‐6P‐S recombinant protein induced strong immune responses in C57BL/6J mice and golden hamsters and sera had cross‐neutralization activity and neutralized wild type and Beta, Delta, Omicron BA.1, BA.2, and BA.5 variant strains. Golden hamsters were immunized against Delta, Omicron BA.1, and BA.2 variants. Viral RNA detected from throat swabs, lungs and tracheas decreased significantly in vaccine‐inoculated animals relative to alum‐treated controls and no infectious viruses were detected in lungs and tracheas. Almost no pathological damage to lung tissue was found in vaccinated animals by contrast with those treated only with alum. The Delta‐6P‐S recombinant protein rapidly eliminated replicating virus in the upper and lower airways of golden hamsters and merits further investigation as a candidate anti‐SARS‐CoV‐2 vaccine.