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

Background: The capacity of pneumococcal vaccination to confer memory in HIV-infected children is critical for durable protection. Methods: HIV-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 ≥0.5. mcg/mL of serotype-specific antibody on day 0 or change from <0.5. mcg/mL to ≥0.5. mcg/mL between day 0 and week 1, or, ≥4-fold antibody rise between day 0 and week 1. Results: Prior to boosting, 4-5 years after the previous PCV7-PCV7-PPV series, geometric mean concentrations (GMCs) were 0.46. mcg/mL (serotype 1), 1.31. mcg/mL (serotype 6B), and 1.47. mcg/mL (serotype 14), with concentrations ≥0.5. mcg/mL in 41% (serotype 1) to 82% (serotypes 6B and 14). Memory based on antibody concentration ≥0.5. mcg/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. Conclusions: Protective 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).