A multicomponent reaction enables the one-pot assembly of immunogenic multivalent glycoconjugates.

Polysaccharide-protein conjugates as vaccines have proven to be very effective in preventing Haemophilus influenzae type b infections in industrialized countries. However, cost-effective technologies need to be developed for increasing the availability of anti-H. influenzae type b vaccines in countries from the developing world. Consequently, vaccine production with partially synthetic antigens is a desirable goal for many reasons. They may be rigidly controlled for purity and effectiveness while at the same time being cheap enough that they may be made universally available. We describe here the antigenicity and immunogenicity of several H. influenzae type b synthetic oligosaccharide-protein conjugates in laboratory animals. The serum of H. influenzae type b-immunized animals recognized our synthetic H. influenzae type b antigens to the same extent as the native bacterial capsular polysaccharide. Compared to the anti-H. influenzae type b vaccine employed, these synthetic versions induced similar antibody response patterns in terms of titer, specificity, and functional capacity. The further development of synthetic vaccines will meet urgent needs in the less prosperous parts of the world and remains our major goal.The advent of conjugate vaccines against Haemophilus influenzae type b-associated diseases has opened a new era in vaccinology (15). These vaccines, which demonstrate excellent immunogenicity, safety, and efficacy in infants, have been obtained by conjugating the capsular polysaccharide polyribosylribitolphosphate from H. influenzae type b to carrier proteins (1,3,8,12). They have been particularly useful in preventing infection with H. influenzae type b in high-risk infant populations. In fact, the almost complete disappearance of H. influenzae type b disease in the developed world together with the corresponding reduction in H. influenzae type b pharyngeal carriage testify to the usefulness of these conjugate vaccines.However, it is extremely difficult to accomplish the progress brought by these commercial vaccines in many poor countries because their high cost reduces both their acquisition and their availability. More than 118 million children are without protection, and only Ϸ2% of cases of H. influenzae type b disease are actually prevented worldwide (15).Given this, H. influenzae type b vaccination in developing countries is urgent but limited by cost and the availability of vaccines. The availability of vaccines depends on producing them with improved technologies and making them affordable to even the poorest societies. In 1989, we embarked on a project to produce a new conjugate anti-H. influenzae type b vaccine from a fully synthetic fragment of the capsular polysaccharide. We have now successfully completed the production, preclinical, and clinical development stages for this new vaccine (17). Here we describe the main preclinical studies that have shown the potential of this new vaccine. Several synthetic H. influenzae type b oligosaccharide-protein conjugates were prepared and their immun...

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