TY - JOUR
T1 - Improving the immunogenicity of pneumococcal conjugate vaccine in HIV-infected adults with a toll-like receptor 9 agonist adjuvant
T2 - a randomized, controlled trial
AU - Søgaard, Ole S
AU - Lohse, Nicolai
AU - Harboe, Zitta B
AU - Offersen, Rasmus
AU - Bukh, Anne R
AU - Davis, Heather L
AU - Schønheyder, Henrik C
AU - Østergaard, Lars
PY - 2010/7/1
Y1 - 2010/7/1
N2 - 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 .
AB - 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 .
KW - AIDS-Related Opportunistic Infections/prevention & control
KW - Adjuvants, Immunologic/pharmacology
KW - Adult
KW - Antiretroviral Therapy, Highly Active
KW - CD4 Lymphocyte Count
KW - Double-Blind Method
KW - Female
KW - HIV Infections/drug therapy
KW - Humans
KW - Immunoglobulin G/blood
KW - Intention to Treat Analysis
KW - Male
KW - Middle Aged
KW - Pneumococcal Vaccines/adverse effects
KW - Pneumonia, Pneumococcal/prevention & control
KW - RNA, Viral
KW - Toll-Like Receptor 9/agonists
KW - Vaccines, Conjugate
U2 - 10.1086/653112
DO - 10.1086/653112
M3 - Journal article
C2 - 20504165
SN - 1058-4838
VL - 51
SP - 42
EP - 50
JO - Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
JF - Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
IS - 1
ER -