Discussion
VIRUS
NVSI-06-09 is a potentially broad-spectrum vaccine using a mosaic-type trimeric RBD protein as the antigen, which combined key mutations from Omicron and other circulating variants into a single molecule. The interim results of the current study showed that a booster injection of NVSI-06-09 in participants who had completed two- or three-dose vaccinations of BBIBP-CorV was safe and well-tolerant. The safety profile of NVSI-06-09 booster was very similar to that of BBIBP-CorV booster, which was also comparable to the safety of two-dose primary vaccination with BBIBP-CorV as reported by Xia et al.WHO has recommended a booster dose or even a second booster dose of COVID-19 vaccine to better combat the pandemic of SARS-CoV-2 (Many previous studies have demonstrated that heterologous booster vaccination may elicit more potent and also broad immune responses than homologous vaccination, especially for inactivated vaccines.To date, COVID-19 vaccines authorized by WHO for emergency use are all targeting the prototype SARS-CoV-2 virus. Numerous studies have shown that after the primary-series vaccination of prototype vaccine, the nAb titers against Beta, Delta, and Omicron variants decreased by 1.07–16.32-fold, 1.0–7.2-fold, and 1.15–109.87-fold, respectively, when compared with that against the prototype virus.Aiming at the defense against the emergence of immune-evasive variants of SARS-CoV-2, several variant-specific vaccines have been developed. Utilizing the inactivated virus-based, mRNA-based, and recombinant protein-based platforms, multiple updated vaccines specific to Beta, Delta, Omicron BA.1 or Omicron BA.2 have been developed.The uncertainty of SARS-CoV-2 evolution may further lead to increased transmissibility, immune evasion properties, and virulence of the virus in the future. It is necessary to accumulate effective technologies to better cope with new variants. The construction of mosaic vaccine may serve as one of the effective strategies against divergent SARS-CoV-2 variants.Our study has some limitations. Firstly, only a small percentage of participants who received two doses of BBIBP-CorV were enrolled in the study. The potential influence of primary dosing frequency of BBIBP-CorV on the immune response boosted by NVSI-06-09 may not be fully revealed. Secondly, very few female volunteers and also very small number of elder individuals participated in the trial, and thus the results obtained may not well reflect the potential immune response in females as well as in elders. Thirdly, NVSI-06-09 is a relatively broad-reactive vaccine, however, it also needs to be updated to maintain high nAb titers when new variants with significant antigenic changes emerge. Fourthly, the clinical data about the long-term immunity are not yet available in this ongoing trial. The results will be reported once the data are obtained.