Home > Programs > Laboratory Sciences > Laboratories
 
1. Introduction
To develop effective vaccines, it is important to understand the protective mechanisms of vaccines and to identify reliable technologies for accurately measuring vaccine efficacy. The Humoral Immunology Section in IVI was initiated March 1, 2004 to study the immunological properties of vaccines and to improve technologies essential for vaccine evaluation. Our current research activities include: 1) elucidation of immune responses to bacterial polysaccharide antigens, 2) development of standardized assays for evaluating vaccine efficacy, and 3) application and improvement of existing diagnostic technologies. Currently, we are working on projects targeting enteric disease such as typhoid fever, cholera, shigellosis and invasive pneumococcal diseases.
 
2. Ongoing projects
2.1. Elucidation of immune responses to bacterial polysaccharide antigens
Most infectious bacteria produce a capsular polysaccharide (PS) surrounding the bacterial cell body. PS is a major virulence factor which protects bacteria from host phagocytosis. Although purified PS (e.g. 23-valent pneumococcal PS vaccine and typhoid Vi PS vaccine) is often used as a vaccine because anti-capsular PS antibody is protective against subsequent infection, however, PS vaccines have limitations including: 1) poor immunogenicity when administered to young children and the elderly, 2) inability to induce germinal center formation necessary for affinity maturation of antibody, 3) poor induction of immune memory response, and 4) induction of immune tolerance. To improve current PS vaccines, we must have better understanding of human immune responses to bacterial PS antigens. We are investigating innate- and adaptive-immune responses to bacterial PS antigens with model antigens such as lipopolysaccharide of Gram-negative bacteria, lipoteichoic acid of Gram-positive bacteria, and their capsular PS.
 
2.2. Development of standardized assays for evaluating vaccine efficacy
Current vaccines are formulated with attenuated whole cells, and their genes or surface antigens, such as polysaccharide capsules, lipidated polysaccharides and surface proteins. For evaluating the efficacy of vaccines, enzyme-linked immunosorbent assays (ELISA) are widely used to measure concentrations of antigen-specific antibodies. Despite the importance of this assay, each laboratory often generates different results in serum antibody levels. These variable results have placed an urgent need on the development of reliable and standardized ELISA. At the same time, because antigen-specific antibody may not be protective against infection, in vitro functional assays (e.g. opsonophagocytic-killing assay or bacteriocidal assay) have been developed for measurement of protective antibody titers following vaccine administration. We are now developing ELISA and the functional assays to provide information on protection induced by typhoid fever, cholera and pneumococcal vaccines.
 
2.3. Application and improvement of existing diagnostic technologies
Currently, definitive diagnosis of bacterial infections is obtained with bacterial culture of biological samples such as sputum, cerebrospinal fluid, blood, bone marrow, and stool. However, bacterial culture-based diagnosis has limitations including: 1) difficulty in obtaining adequate clinical specimens from patients, particularly infants and young children, and 2) the possibility that bacterial blood cultures may yield no growth of pathogenic bacteria due either to inadequate culture technique or to inappropriate use of antibiotics. Our research in this area is aimed at improvement of diagnostic technologies based on identification of microbial products (e.g. bacterial antigens) and analysis of host immune response. For these studies, we are working on sero-diagnosis to quantify antibody against etiologic agents in biological fluids, reverse transcription-polymerase chain reaction to detect microbial genes, and immuologic assays to detect bacterial polysaccharides or proteins.