During the last three decades, the development and commercialization of conjugate vaccines against Haemophilus influenzae type b (Hib), pneumococcus, and serogroups C, A, W, and Y of meningococcus contributed to the virtual elimination of bacterial meningitis caused by the bacteria included in the vaccines and to the prevention of diseases that used to cause more than a million deaths annually (1, 2). Despite the great impact on public health of these vaccines, our understanding of the way these vaccines work is still limited, and we have many unanswered questions. In PNAS, Sun et al. (3) report new mechanistic insights on conjugate vaccines. Conjugate vaccines have been developed to induce a robust immune response against bacterial capsular polysaccharides (CPSs). CPSs are long polymers composed of many repeating units of simple sugars and serve as a protective external layer for many bacteria. Depending on the chemical composition of the repeating unit (usually composed of one to seven monosaccharides). Bacteria can synthesize hundreds of chemically and immunologically different polysaccharides. Antibodies against the polysaccharides of many pathogenic bacteria, such as meningococcus, Hib, and pneumococcus, protect people from disease. Vaccines composed of purified polysaccharides against meningococcus and pneumococcus were developed in the 1970s. Unfortunately, those vaccines, while partially immunogenic in adults, were completely unable to induce an antibody response in infants and children, the population for whom the vaccines were mostly needed. The problem was solved in the 1980s when John Robbins and Rachel Schneerson at the National Institutes of Health in Bethesda, Maryland, and David Smith and Porter Anderson in Rochester, New York, independently figured out that, in 1929, it had been reported that bacterial CPSs become very immunogenic when covalently linked to a carrier protein (4, 5) and, thus, started working on a conjugate vaccine against Hib, which worked beautifully in … [↵][1]1To whom correspondence should be addressed. Email: rino.r.rappuoli{at}gsk.com. [1]: #xref-corresp-1-1