Related Experiment Videos
Correlation between antibody affinity and serum bactericidal activity in infants
1Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee 38101.
Insights
Nearly half of infants develop low-affinity antibodies after Haemophilus influenzae type b (Hib) conjugate vaccination. Antibody affinity, not concentration, significantly correlated with protective bactericidal activity, indicating functional deficiency in some infant immune responses.
Area of Science:
- Immunology
- Pediatrics
- Vaccinology
Background:
- Infants immunized with Haemophilus influenzae type b (Hib) capsular polysaccharide (polyribosylribitol phosphate; PRP)-protein conjugate vaccines often produce low-affinity antibodies.
- The functional significance of antibody affinity in the context of Hib conjugate vaccination in infants remains unclear.
Purpose of the Study:
- To investigate the relationship between antibody affinity and biologic function, specifically bactericidal activity, in infants immunized with a Hib conjugate vaccine.
- To determine if antibody affinity is a critical factor in the protective immune response against Hib.
Main Methods:
- Sera were collected from 18-month-old infants before and one month after immunization with a PRP-diphtheria toxoid conjugate vaccine.
- Assays were performed to measure anti-PRP antibody affinity, anti-PRP and anti-outer membrane protein concentrations, immunoglobulin isotype, and serum bactericidal activity.
- Multiple regression analysis was used to correlate these parameters with bactericidal activity.
Main Results:
- Nine subjects had low-affinity anti-PRP antibodies (K < 10(4) l/mol), while 11 had higher affinity antibodies (average K = 2.8 x 10(4) l/mol).
- Multiple regression analysis revealed that antibody affinity was the only variable significantly associated with serum bactericidal activity post-vaccination (r = .71; P = .04).
- Neither antibody concentration nor immunoglobulin isotype showed a significant correlation with bactericidal activity.
Conclusions:
- A substantial proportion of infants immunized with Hib conjugate vaccine produce functionally deficient serum antibodies due to low affinity.
- Antibody affinity is a critical determinant of protective immunity elicited by Hib conjugate vaccines in infants.
- These findings highlight the importance of antibody affinity in evaluating vaccine efficacy and infant immune responses.
Abstract:
Nearly one-half of infants immunized with Haemophilus influenzae b capsular polysaccharide (polyribosylribitol phosphate; PRP)-protein conjugate produce low-affinity antibody. To test the hypothesis that antibody affinity is linked to biologic function, sera were obtained before and 1 month after immunization of 18-month-old infants with PRP-diphtheria toxoid conjugate vaccine. Correlation was attempted of anti-PRP affinity, concentrations of anti-PRP, and anti-outer membrane proteins and of immunoglobulin isotype with bactericidal activity. Nine subjects produced anti-PRP of low affinity (K less than 10(4) l/mol), and 11 had higher affinity antibodies (average K, 2.8 x 10(4) l/mol). By multiple regression analysis, antibody affinity was the only variable significantly related to the bactericidal activity of serum after immunization with the conjugate vaccine (r = .71; P = .04). Thus, serum anti-PRP from a substantial proportion of infants appeared functionally deficient in association with low-affinity antibody.