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document
Improving the immunogenicity of pneumococcal conjugate vaccine in HIV-infected adults with a toll-like receptor 9 agonist adjuvant : a randomized , controlled trial . BACKGROUND Persons infected with human immunodeficiency virus ( HIV ) are often hyporesponsive to immunization , including pneumococcal vaccines . We hypothesized that adding CPG 7909 , a toll-like receptor 9 ( TLR9 ) agonist and vaccine adjuvant , to 7-valent pneumococcal conjugate vaccine ( 7vPnC ) would increase its immunogenicity in HIV-infected adults . METHODS We performed a double-blind , placebo-controlled , phase 1b/2a trial randomizing HIV-positive patients to receive double doses of 7vPnC ( Prevnar ) at 0 and 3 months and 1 dose of 23-valent pneumococcal polysaccharide vaccine ( PPV-23 ; Pneumo Novum ) at 9 months , with experimental patients receiving 1 mg of CPG 7909 added to each of their 3 vaccine doses ; control patients had phosphate-buffered saline added instead . Immunogenicity and safety were evaluated for up to 10 months . The primary end point was the proportion of vaccine high responders at 9 months , defined as a 2-fold increase in IgG levels to > or = 1 microg/mL for at least 5 of 7 of the 7vPnC serotypes . RESULTS Ninety-seven participants were included in the study . The proportion of vaccine high responders was higher in the experimental group ( n = 48 ) than among controls ( n = 49 ; 48.8 % vs 25.0 % ; P = .02 ) at 9 months . Greater proportions of high responders were also observed at 3 ( 51.1 % vs 39.6 % ; P = .26 ) , 4 ( 77.3 % vs 56.3 % ; P = .03 ) , and 10 months ( 87.8 % vs 51.1 % ; P < .001 ) . Mild systemic and injection site reactions to 7vPnC were more common in the experimental group than the control group ( 100 % vs 81.3 % ; P = .002 ) . CPG 7909 did not increase non-7vPnC IgG levels after PPV-23 immunization . No adverse effects on CD4 ( + ) cell count or organ functions occurred in either group . CONCLUSIONS The addition of a TLR9 agonist to 7vPnC significantly enhanced the proportion of vaccine high responders . TRIAL REGISTRATION ClinicalTrials.gov identifier : NCT00562939 .
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Intervention_Control
placebo-controlled
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Intervention_Pharmacological
7vPnC ( Prevnar )
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Intervention_Pharmacological
23-valent pneumococcal polysaccharide vaccine ( PPV-23 ; Pneumo Novum )
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Intervention_Pharmacological
CPG 7909
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Intervention_Pharmacological
phosphate-buffered saline
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Intervention_Pharmacological
7vPnC
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Intervention_Pharmacological
PPV-23
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Intervention_Pharmacological
TLR9
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Intervention_Pharmacological
7vPnC
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Outcome_Physical
immunogenicity
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Outcome_Physical
Immunogenicity
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Outcome_Physical
safety
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Outcome_Physical
proportion of vaccine high responders at 9 months
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Outcome_Physical
proportion of vaccine high responders
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Outcome_Physical
proportions of high responders
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Outcome_Physical
Mild systemic and injection site reactions
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Outcome_Physical
non-7vPnC IgG levels
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Outcome_Physical
CD4 ( + ) cell count
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Outcome_Physical
organ functions
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Outcome_Physical
vaccine high responders