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Single-cell RNA sequencing allows highly detailed profiling of cellular immune responses from limited-volume samples, advancing prospects of a new era of systems immunology. The power of single-cell RNA sequencing offers various opportunities to decipher the immune response to infectious diseases and vaccines. Here, we describe the potential uses of single-cell RNA sequencing methods in prophylactic vaccine development, concentrating on infectious diseases including COVID-19. Using examples from several diseases, we review how single-cell