Do all antibodies detected by a pneumococcal antibody test actually protect against infection?

Details

The researchers had previously shown that a substantial proportion of antibody to pneumococcal polysaccharide measured by enzyme-linked immunosorbent assay (ELISA) or radioimmunoassay could be removed by adsorption with pneumococcal cell wall polysaccharide (CWPS). This study tested the hypothesis that only serotype-specific antibody remaining after CWPS adsorption protects against pneumococcal infection.

In this experimental mouse protection study, serum was collected from human subjects before and after pneumococcal polysaccharide vaccination. Antibody to Streptococcus pneumoniae serotype 4 was measured by ELISA either without adsorption or after serum adsorption with CWPS. Groups of mice received graded doses of serum and were then challenged intraperitoneally with 10, 100, or 1,000 median lethal doses (LD50, the dose lethal to 50%) of S. pneumoniae serotype 4.

Without adsorption, prevaccination serum from five healthy adults appeared to contain up to 33 micrograms of antibody to S. pneumoniae serotype 4 antigen per ml. CWPS adsorption removed all detectable antibody. Pretreating mice with up to 0.1 ml of these sera, containing an apparent antibody amount of no more than 3.3 micrograms, failed to protect them against a 100 LD50 challenge.

In contrast, postvaccination sera contained 2.9 to 30 micrograms of antibody per ml that was not removed by adsorption. The researchers diluted sera to administer specified amounts of serotype-specific immunoglobulin G (IgG). Protection was significantly related to the antibody remaining after adsorption (P < 0.05, linear regression analysis): 150 ng was uniformly protective against 1,000 LD50, and 50 ng was protective against 100 LD50.

The authors described this as the first quantification of the amount of serotype-specific antibody that protects mice against S. pneumoniae type 4 challenge. They concluded that these observations call for reassessing current concepts about antipneumococcal antibody in the unvaccinated population, responses to pneumococcal vaccination, and protective IgG levels.