In the light of the lack of authorized COVID-19 vaccines adapted to the Omicron variant lineage, the administration of the first and second booster dose is recommended. It remains important to monitor the efficacy of such an approach in order to inform future preventive strategies. The present paper summarizes the research progress on the effectiveness of the first and second booster doses of COVID-19. It also discusses the potential approach in vaccination strategies that could be undertaken to maintain high levels of protection during the waves of SARS-CoV-2 infections. Although this approach can be based, with some shortcomings, on the first-generation vaccines, other vaccination strategies should be explored, including developing multiple antigen-based (multivariant-adapted) booster doses with enhanced durability of immune protection, e.g., through optimization of the half-life of generated antibodies.