A sweeter approach to vaccine design

Glycoengineering may improve next-generation vaccines and immunotherapies Vaccines have transformed human health. Yet, guided primarily by empiricism for centuries, vaccine design ultimately met its match in scourges such as HIV, tuberculosis, and malaria, which continue to plague global health. The elusive search for vaccines against such diseases has driven researchers of diverse expertise to forgo empirical vaccinology. Instead, they favor a reductionist approach inspired by how pathogens interact with the immune system, which has evolved to distinguish foreign from self by sensing both physical (e.g, size) and chemical (e.g., foreign molecules) features of pathogens. This has guided the rational design of vaccines that mimic key pathogen properties, including arraying antigens on particles to increase recognition by antibody-producing B cells ( 1 ). However, the mechanisms by which multivalent antigen display on nanoparticles—either synthetic or natural—enhances immunity, and how this may influence vaccine design principles, remain unresolved. On page 649 of this issue, Tokatlian et al. ( 2 ) help fill this knowledge gap by demonstrating that engineering nanoparticles with glycans—sugar molecules—is critical to potentiating antibody responses. This might lead to improved next-generation vaccines against a wide diversity of pathogens.