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

• Published in: Vaccine Vol. 31; no. 42; pp. 4782 - 4790
• Main Authors: Abzug, Mark J., Song, Lin Ye, Levin, Myron J., Nachman, Sharon A., Borkowsky, William, Pelton, Stephen I.
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 01.10.2013; Elsevier; Elsevier Limited
• Subjects: Adolescent; Allergy and Immunology; antibodies; Antibodies, Bacterial - blood; Antibody Affinity; Antiretroviral agents; Antiretroviral drugs; Antiretroviral Therapy, Highly Active; Applied microbiology; Bacteriology; Biological and medical sciences; Child; Children; Children & youth; clinical trials; Drug therapy; Enzyme-Linked Immunosorbent Assay; Female; Fundamental and applied biological sciences. Psychology; HIV; HIV infections; HIV Infections - drug therapy; HIV Infections - immunology; Human immunodeficiency virus; Human viral diseases; Humans; Immunization; Immunologic Memory; Infectious diseases; Male; Medical sciences; Memory; Microbiology; Miscellaneous; Pneumococcal; Pneumococcal Infections - immunology; Pneumococcal Infections - prevention & control; Pneumococcal Vaccines - administration & dosage; Pneumococcal Vaccines - immunology; serotypes; Streptococcus pneumoniae; vaccination; Vaccination - methods; Vaccine; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; viral load; Young Adult; Pneumococcal; PCV; HIV; Memory; VL; PPV; Vaccine; Children; viral load; pneumococcal polysaccharide vaccine; pneumococcal conjugate vaccine; Human; Immunopathology; Antibody; Vaccination; Retroviridae; AIDS; Immune deficiency; Lentivirus; Streptococcus pneumoniae; Infection; Virus; Streptococcaceae; Viral disease; Bacteria; Micrococcales; Antiviral; Human immunodeficiency virus; Child; Polysaccharide
• ISSN: 0264-410X; 1873-2518; 1873-2518
• DOI: 10.1016/j.vaccine.2013.08.002

•HIV-infected children were studied following pneumococcal vaccination on HAART.•Subjects received 2 conjugate (PCV) and 1 polysaccharide (PPV) vaccine doses.•4–5 years later, most had protective antibody concentrations for PCV serotypes.•Antibody responses following a PCV or PPV booster were indicative of memory.•Antibody measured was primarily high avidity antibody. The capacity of pneumococcal vaccination to confer memory in HIV-infected children is critical for durable protection. 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 ≥0.5mcg/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. Prior 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. 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).