Overview

Bacterial pathogens, such as Streptococcus pneumonia, cause significant morbidity and mortality worldwide. Vaccination against these organisms is often least effective in those groups most at risk, such as infants and the elderly. Dr. Reason’s research examines at the molecular and structural level those factors that determine the quality of antibodies induced by vaccination, and seeks to determine regulatory factors that limit vaccine effectiveness in certain populations.
Research at CHORI and elsewhere has shown that vaccination with the capsular polysaccharides of important bacterial pathogens induces a limited and highly restricted antibody response, even in those populations that respond well to vaccination. This is in part due to the relatively simple, repetitive nature of the polysaccharide antigens, and in part due to the way these antigens are handled by the human immune system. Reason and colleagues at CHORI have begun to (1) identify the specific genetic elements used to encode pneumococcal-specific human antibodies, (2) determine how mutations occurring during the course of the antibody response affect the avidity of specific antibodies for their target bacterial antigens, (3) measure the contribution to specificity by individual residues within the antibody-combining site, and (4) quantitate the combined effect of the above factors on antibody quality.

The pneumococcal vaccines, along with contemporary methodologies in cellular and molecular immunology, are allowing fundamental questions of human immune mechanisms to be addressed as they apply to these important bacterial pathogens.