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

Abstract

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.

Trial registration: ClinicalTrials.gov NCT00257127.

Keywords: Children; HIV; Memory; PCV; PPV; Pneumococcal; VL; Vaccine; pneumococcal conjugate vaccine; pneumococcal polysaccharide vaccine; viral load.

Figure 1

Persistence of antibody between P1024 and P1061s. Geometric mean concentrations and confidence intervals are shown for each of the three serotypes evaluated. Timepoints are at weeks -212, -188, and -140 relative to P1061s entry (8, 32, and 80 weeks after the conclusion of the PCV7-PCV7-PPV regimen in P1024) and at P1061s entry (week 0; a median of 220 weeks after the conclusion of the PCV7-PCV7-PPV series at P1024 week 16). Panel (a) depicts all immune strata combined for the three serotypes and panels (b) – (d) show the immune strata separately for each serotype. Immune stratum 1, which contained only one subject, is excluded from panels (b) – (d). Seventy-nine subjects were assessed at week -212, 73 at week -188, 70 at week -140, and 79 at week 0. The percent with antibody concentration ≥0.5 mcg/mL (% Seropos) at each timepoint are displayed below panel (a) for the three serotypes (STs; all immune strata combined) and below panels (b) – (d) for each immune stratum (excluding stratum 1). Note: the y-axis scale in panels (a) and (b) extends to 5 mcg/mL, while the y-axis scale in panels (c) and (d) extend to 12 mcg/mL.