Paul Kovac, Ph.D., Dr. h.c.

The purpose of my research is to develop/improve methods for chemical attachment of carbohydrates to suitable carriers, and design protocols for making conjugate vaccines for infectious bacterial diseases from synthetic and bacterial carbohydrate antigens. Such vaccines are often free from undesirable traditional bacterial vaccines often have. Some neoglycoconjugates we prepare can be used as diagnostic tools to identify presence of pathogens.

Current Research

Our primary focus is to further the development of conjugate vaccines from synthetic and bacterial carbohydrate antigens. Ultimately, we would like to develop reliable protocols for preparation of neoglycoconjugates that could become substitutes for traditional vaccines based on whole-cell killed or attenuated bacteria. Such vaccines are often pyrogenic or have other undesirable effects. As synthetic carbohydrate antigens, we use oligosaccharides that mimic the structure of polysaccharides present on the surface of bacterial pathogens. As bacterial bacterial antigens we use protective antigen-containing fragments of lipopolysacchardies (LPS). Because there is virtually an infinite number of choice of architectonic details that a synthetic neoglycoconjugate can incorporate, part of our work involves studies of the effects of variables such as size of the carbohydrate antigen, type of linker, linking chemistry, type of carrier, etc., upon immunogenicity and protective capacity. In addition to obtaining potent immunogens, we expect our studies to result in findings of general utility in synthetic vaccine preparation.

With synthetic fragments of LPS, our approach involves five stages:

1. Synthesis of fragments of antigenic polysaccharides and the deoxy and deoxyfluoro analogs of those fragments
2. Studies of binding the above ligands with antibodies to the native antigen and identification of critical hydrogen bonding interactions
3. Identification of the immunologically dominant oligosaccharide sequence in the antigenic polysaccharide
4. Chemical conjugation of such fragment(s) to suitable carrier(s), to obtain neoglycoconjugates
5. Probing the antigenicity, immunogenicity, and protective capacity of neoglycoconjugate(s)

With bacterial LPS, our approach involves:

1. Detoxification of LPS by mild acid hydrolysis to remove lipid A and arrive at O-SP–core fragment (O-SPc) of the LPS
2. Purification of O-SPc
3. Conjugation of O-SPc to a suitable protein carrier
4. Probing the antigenicity, immunogenicity, and protective capacity of neoglycoconjugate(s)

Our section has studied the interaction of carbohydrate antigens and antibodies for many years using the above approach. As a result, we have been able to obtain a great deal of detailed information on binding at the molecular level. Following the same concept, groundwork was laid for development of immunogens for Shigella dysenteria type 1. The current objective of our work is development of synthetic vaccines for cholera and other enteric diseases, and anthrax.

In addition, we often engage in collaborative research, within the United States and internationally, with universities and other scientific institutions.

Applying our Research

Safer vaccines and better diagnostic tools that we aim to develop translate into improved public health.

Need for Further Study

Further areas of study include optimization of the conjugation protocol, identification of the optimal structure of the conjugate vaccine and immunization schedule in order to deliver the optimal amount of antigen necessary to elicit protective level of antibodies.

• Senior Investigator, Laboratory of Bioorganic Chemistry, NIDDK, NIH, 1983-present
• Group Leader, Bachem, Inc., 1981-1982
• Senior Scientist, Institute of Chemistry, Slovak Academy of Sciences, 1969-1981
• Post-doctoral Fellow, Purdue University, Department of Biochemistry, 1967-1968
• Ph.D., Institute of Chemistry, Slovak Academy of Sciences, 1967
• M.S., Slovak Technical University, 1962