AIDSWEEKLY Plus; Monday, October 5, 1998
Daniel J. DeNoon, Senior Editor
The finding comes from a molecular analysis of antibodies produced by healthy adults in response to Streptococcus pneumoniae capsular polysaccharides (PPS).
"These studies have begun to define the genetic and functional bases of PPS-specific antibody repertoires and have established an experimental foundation for dissecting the relationship between pneumococcal antibody structure and protective function," noted Alexander H. Lucas of the Oakland Research Institute, Oakland, California.
Lucas reported data from these investigations in a presentation to the American Society for Microbiology's 38th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), held September 24- 27, 1998, in San Diego, California.
Although Phase III clinical trials of pneumococcal conjugate vaccines are underway (see accompanying story), the correlates of immunity to pneumococci are poorly understood.
Lucas and colleagues studied the genetic bases and functions of protective antibodies to PPS serotypes 613, 14, and 23F. Their findings indicated that serum antibodies against PPS seem to come from only a small number of B-cell clones.
"These findings indicate individually restricted variable-region expression and suggest that antibody functional capacity could be skewed," Lucas observed.
The researchers isolated PPS-specific antibody fragments (FAbs) and sequenced their variable (V) regions and determined their PPS- binding function.
The V regions were found to be members of the large V[H]3 subgroup. The binding data showed that PPS affinity correlated with usage of specific V regions. Moreover, there was a positive correlation between anti-PPS avidity and protective function as demonstrated by phagocytosis of pneumococci and by protection of mice from lethal pneumococcal challenge.
"Antibody avidity is an important determinant of immunity to pneumococci," Lucas concluded.
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