Antibody persistence and immunologic memory after sequential pneumococcal conjugate and polysaccharide vaccination in HIV-infected children on highly active antiretroviral therapy

Abstract

BackgroundThe capacity of pneumococcal vaccination to confer memory in HIV-infected children is critical for durable protection. MethodsHIV-infected children 2–<19 years administered two doses of pneumococcal conjugate vaccine (PCV7) and one dose of polysaccharide vaccine (PPV) on HAART were randomized 4–5 years later to receive a PCV7 or PPV booster. Total and high avidity antibodies to serotypes 1 (PPV) and 6B and 14 (PCV7 and PPV) were determined by ELISA. Memory was defined as persistence of ≥0.5mcg/mL of serotype-specific antibody on day 0 or change from <0.5mcg/mL to ≥0.5mcg/mL between day 0 and week 1, or, ≥4-fold antibody rise between day 0 and week 1. ResultsPrior to boosting, 4–5 years after the previous PCV7-PCV7-PPV series, geometric mean concentrations (GMCs) were 0.46mcg/mL (serotype 1), 1.31mcg/mL (serotype 6B), and 1.47mcg/mL (serotype 14), with concentrations ≥0.5mcg/mL in 41% (serotype 1) to 82% (serotypes 6B and 14). Memory based on antibody concentration ≥0.5mcg/mL before or 1 week after boosting with PCV7 or PPV was demonstrated in 42–61% for serotype 1 and 87–94% for serotypes 6B and 14, with lower rates based on day 0 to week 1 ≥4-fold antibody rise (serotype 1, 3–13%; serotype 6B, 13–31%; serotype 14, 29–53%). Antibody concentrations post-boosting were greater following PCV7 than PPV for serotypes 6B and 14. Ratios of highly avid to total antibody pre- and post-boosting were 0.5–0.8. Predictors of memory included higher CD4% (nadir before HAART and at P1024 and P1061s entry), CD19% (at P1024 and P1061s entry), and antibody response after the PCV7-PCV7-PPV primary series and lower viral load (at P1024 and P1061s entry) and age. ConclusionsProtective antibody concentrations, high avidity, and booster responses to PCV7 or PPV indicative of memory were present 4–5 years after PCV7-PCV7-PPV in HIV-infected children on HAART.Clinical Trials Registration: NCT00257127 (www.clinicaltrials.gov).