The study enrolled a priori four groups of children aged 6 to 12 weeks. These included 2 groups of HIV infected infants, co-enrolled from the C hildren with H IV E arly Antir etroviral (CHER) Study in South Africa, 5 (link) with CD4+ T-lymphocyte cells ≥25% randomized to initiate ART immediately (HIV+/ART+ group); or ART was initiated when clinically or immunologically indicated (HIV+/ART− Group). 6 The ART regimen included zidovudine, lamivudine and lopinavir/ritonavir. Additionally, two cohorts of HIV non-infected infants were prospectively enrolled in parallel to the HIV infected children including: i. infants born to HIV infected mothers who were HIV PCR (Roche Amplicor Version 1.5 RNA PCR) negative at baseline and one month after the third dose of Vaccine (M+/I−) and ii. infants born to mothers seronegative for HIV after 24 weeks of gestational age during pregnancy and who were HIV ELISA seronegative at study-enrolment (i.e. M−/I−).
Additional participant-eligibility criteria included absence of intercurrent illness within 72 hours of enrolment, no Grade 3 or 4 clinical or laboratory toxicity as per DAIDS Pediatric Adverse Experiences,7 birth weight of at least 2000 grams, participation in the CHER study for HIV infected infants, absence of receipt of any blood products prior to study entry, any immunomodulating medication for more than two weeks within one week of possible enrolment
Infants were enrolled between April 2005 and June 2006 and scheduled to receive three doses of 7-valent pneumococcal conjugate vaccine (i.e. Prevnar®; Wyeth Vaccines, NJ, USA) at 6 to 12, 9 to 18 and 12 to 24 weeks of age. Infants received other scheduled childhood vaccines, included in the public immunization program, concurrently with Prenar®.
Immune response to the primary series of Vaccine was measured 3 to 6 weeks after the third dose using serum from venous blood which had been centrifuged, aliquotted and stored at –20 to −70°C until processing at the Respiratory and Meningeal Pathogens Research Unit (RMPRU), Johannesburg, South Africa. A standardized enzyme immunoassay (EIA), including adsorption with 22F polysaccharide, was used to test for vaccine-serotype specific capsular IgG antibody concentrations as described. 8 (link) 9 (link)
The functionality of the antibodies post vaccination was determined by opsonophagocytic killing assay (OPA) for serotypes 9V, 19F and 23F using differentiated HL-60 cells as described.8 (link) 10 (link) Lower antibody concentrations required for 50% killing activity on OPA is suggestive of superior antibody functional activity. Detectable killing activity on OPA was defined as a titer of ≥8.
For quality assurance, a quality control serum from a vaccinated volunteer was included on each plate. The coefficient of variation for the control sera were <40% for all serotypes.
Additional participant-eligibility criteria included absence of intercurrent illness within 72 hours of enrolment, no Grade 3 or 4 clinical or laboratory toxicity as per DAIDS Pediatric Adverse Experiences,7 birth weight of at least 2000 grams, participation in the CHER study for HIV infected infants, absence of receipt of any blood products prior to study entry, any immunomodulating medication for more than two weeks within one week of possible enrolment
Infants were enrolled between April 2005 and June 2006 and scheduled to receive three doses of 7-valent pneumococcal conjugate vaccine (i.e. Prevnar®; Wyeth Vaccines, NJ, USA) at 6 to 12, 9 to 18 and 12 to 24 weeks of age. Infants received other scheduled childhood vaccines, included in the public immunization program, concurrently with Prenar®.
Immune response to the primary series of Vaccine was measured 3 to 6 weeks after the third dose using serum from venous blood which had been centrifuged, aliquotted and stored at –20 to −70°C until processing at the Respiratory and Meningeal Pathogens Research Unit (RMPRU), Johannesburg, South Africa. A standardized enzyme immunoassay (EIA), including adsorption with 22F polysaccharide, was used to test for vaccine-serotype specific capsular IgG antibody concentrations as described. 8 (link) 9 (link)
The functionality of the antibodies post vaccination was determined by opsonophagocytic killing assay (OPA) for serotypes 9V, 19F and 23F using differentiated HL-60 cells as described.8 (link) 10 (link) Lower antibody concentrations required for 50% killing activity on OPA is suggestive of superior antibody functional activity. Detectable killing activity on OPA was defined as a titer of ≥8.
For quality assurance, a quality control serum from a vaccinated volunteer was included on each plate. The coefficient of variation for the control sera were <40% for all serotypes.
