Challenges and developments in universal vaccine design against SARS-CoV-2 variants

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had become a global concern because of its unexpectedly high pathogenicity and transmissibility. SARS-CoV-2 variants that reduce the immune protection elicited from previous vaccination or natural infection raise challenges in controlling the spread of the pandemic. The development of universal vaccines against these variants seems to be a practical solution to alleviate the physical and economic effects caused by this disease, but it is hard to achieve. In this review, we describe the high mutation rate of RNA viruses and dynamic molecular structures of SARS-CoV-2 variants in several major neutralizing epitopes, trying to answer the question of why universal vaccines are difficult to design. Understanding the biological basis of immune evasion is crucial for combating these obstacles. We then summarize several advancements worthy of further study, including heterologous prime-boost regimens, construction of chimeric immunogens, design of protein nanoparticle antigens, and utilization of conserved neutralizing epitopes. The fact that some immunogens can induce cross-reactive immune responses against heterologous coronaviruses provides hints for universal vaccine development. We hope this review can provide inspiration to current universal vaccine studies.