Abstract::The application of single-cell analysis to investigate immune cell diversity has historically
been considered a complex task. Recently, innovative techniques have emerged revolutionizing
the way immune cells can be explored, offering unprecedented insights into the dynamics of
this complex system. In particular, novel approaches have enabled a detailed characterization of
B-cell responses, encompassing immune repertoire, gene expression, and phenotype analysis at an
individual cell level. By analyzing single B-cells, researchers can unravel their heterogeneity,
trace clonal evolution, and track immune responses during infections and vaccinations over time,
gaining a deeper understanding of the mechanisms underlying antibody secretion and immune memory
formation. This knowledge can inform the development of optimal immunogens, adjuvants,
and vaccine platforms, which are crucial for inducing robust, long-lasting protective responses
and overcoming existing challenges in vaccine research. This is particularly valuable for rational
vaccine design against certain pathogens, such as human immunodeficiency virus [HIV-1], for
which a successful vaccine remains to be developed due to the need to elicit rare broadly neutralizing
antibodies that target conserved epitopes on the genetically diverse envelope glycoprotein
trimer. This review will highlight the latest advancements in single-cell sequencing techniques
and bioinformatic tools for the analysis of B-cell responses in the context of infectious diseases
and vaccinations. Single-cell sequencing techniques, their applications, and their pivotal role in advancing
the design of next-generation vaccines, especially in the context of HIV-1, will be discussed.