The primary focus of the Carbohydrates Section in the NIDDK’s Bioorganic Chemistry Laboratory is to develop safer, highly effective vaccines. Instead of using actual disease-causing organisms that have been killed or attenuated, we use in vaccine development antigens that have been synthesized especially for this purpose. Alternatively, we use carbohydrates obtained from chemically modified bacterial lipopolysaccharides. Vaccines made from whole cell killed or weakened disease organismscan often cause high fevers (they are pyrogenic) or have other undesirable side effects.
Sometimes the outer coat of an actual disease-causing organism is not the optimal antigen (a substance that causes your immune system to produce antibodies against it) for a strong immune response. In order to enhance this response, the carbohydrate portion of this bacterial coating can be combined (or conjugated) with a suitable carrier, often after removal of its toxic part, Lipid A . The material resulting from conjugation is called a neoglycoconjugate.
Our preferred approach is to create a synthetic carbohydrate molecule—a synthetic oligosaccharide—that is chemically similar to the carbohydrate coat of the actual disease-causing organism and evokes a strong immune response when it is conjugated to a carrier. Because it does not contain any, potentionally harmful fragments of the bacterial pathogen, the construct resulting from linking together purified synthetic oligosaccharide and a purified carrier does not have pyrogenic or other undesirable side effects. Our current objective is to develop safe conjugate vaccines for two deadly diseases, cholera and anthrax, using such synthetic components.
There are many ways for syntheizing synthetic oligosaccharides that mimic the carbohydrate bacterial coat and linking them to a carrier. Therefore, part of our work is to study how various factors, such as the size of the carbohydrate fragment and mode of linking, affect the ability of the conjugated vaccine to evoke a strong protective immune response in a vaccinated person. For many years, we have used a systematic, staged approach to develop synthetic oligosaccharides and the conjugate vaccines made from them. This approach starts with synthesizing fragments of the weakly antigenic carbohydrate coat of the disease organism, finding the fragments that evoke the strongest production of effective antibodies, and conjugating these fragments to suitable carriers. We then test how well this conjugated compound works as a protective vaccine.