Journal Article

Improving the Immunogenicity of Pneumococcal Conjugate Vaccine in HIV-Infected Adults with a Toll-Like Receptor 9 Agonist Adjuvant: A Randomized, Controlled Trial

Ole S. Søgaard, Nicolai Lohse, Zitta B. Harboe, Rasmus Offersen, Anne R. Bukh, Heather L. Davis, Henrik C. Schønheyder and Lars Østergaard

in Clinical Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 51, issue 1, pages 42-50
Published in print July 2010 | ISSN: 1058-4838
Published online July 2010 | e-ISSN: 1537-6591 | DOI: http://dx.doi.org/10.1086/653112
Improving the Immunogenicity of Pneumococcal Conjugate Vaccine in HIV-Infected Adults with a Toll-Like Receptor 9 Agonist Adjuvant: A Randomized, Controlled Trial

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  • Infectious Diseases
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  • Public Health and Epidemiology
  • Microbiology

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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 ⩾1 µg/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.

Journal Article.  4451 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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