Abstract
Serotype-specific antibody responses to unconjugated pneumococcal polysaccharide vaccine (PPV) evaluated by a World Health Organization (WHO)-standardized enzyme-linked immunosorbent assay (ELISA) are the gold standard for diagnosis of specific polysaccharide antibody deficiency (SAD). The American Academy of Allergy, Asthma and Immunology (AAAAI) has proposed guidelines to interpret the PPV response measured by ELISA, but these are based on limited evidence. Additionally, ELISA is costly and labor-intensive. Measurement of antibody response to Salmonella typhi (S. typhi) Vi vaccine and serum allohemagglutinins (AHA) have been suggested as alternatives. However, there are no large cohort studies and cutoff values are lacking. To establish cutoff values for antipneumococcal polysaccharide antibody response, anti-S. typhi Vi antibody, and AHA. One hundred healthy subjects (10-55 years) were vaccinated with PPV and S. typhi Vi vaccine. Blood samples were obtained prior to and 3-4 weeks after vaccination. Polysaccharide responses to 3 serotypes were measured by WHO ELISA and to 12 serotypes by an in-house bead-based multiplex assay. Anti-S. typhi Vi IgG were measured with a commercial ELISA kit. AHA were measured by agglutination method. Applying AAAAI criteria, 30% of healthy subjects had a SAD. Using serotype-specific fifth percentile (p5) cutoff values for postvaccination IgG and fold increase pre- over postvaccination, only 4% of subjects had SAD. One-sided 95% prediction intervals for anti-S. typhi Vi postvaccination IgG (≥11.2 U/ml) and fold increase (≥2) were established. Eight percent had a response to S. typhi Vi vaccine below these cutoffs. AHA titer p5 cutoffs were ½ for anti-B and ¼ for anti-A. We establish reference cutoff values for interpretation of PPV response measured by bead-based assay, cutoff values for S. typhi Vi vaccine responses, and normal values for AHA. For the first time, the intraindividual consistency of all three methods is studied in a large cohort.
Highlights
Vaccine responses to polysaccharide vaccines are important for the diagnosis and management of patients with suspected primary immunodeficiencies (PID) [1]
The American Academy of Allergy, Asthma and Immunology (AAAAI) has proposed guidelines to interpret the pneumococcal polysaccharide vaccine (PPV) response measured by enzyme-linked immunosorbent assay (ELISA), but these are based on limited evidence
We established cutoff values for an adequate response to S. typhi Vi vaccine and AHA (IgG and IgM) in the largest healthy population reported to date (n = 100)
Summary
Vaccine responses to polysaccharide vaccines are important for the diagnosis and management of patients with suspected primary immunodeficiencies (PID) [1]. A diagnosis of SAD is made when there is an isolated defect of the pneumococcal polysaccharide response with normal responses to protein and conjugate vaccines and normal immunoglobulin levels [3]. Patients with SAD suffer from recurrent bacterial respiratory tract infections, such as sinusitis, otitis with chronic otorrhea, bronchitis, or pneumonia. Patients with increased susceptibility to infections and deficient polysaccharide response can be treated with prophylactic antibiotics, immunoglobulin replacement therapy, or both. Serotype-specific antibody responses to unconjugated pneumococcal polysaccharide vaccine (PPV) evaluated by a World Health Organization (WHO)standardized enzyme-linked immunosorbent assay (ELISA) are the gold standard for diagnosis of specific polysaccharide antibody deficiency (SAD). There are no large cohort studies and cutoff values are lacking
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