Improved Immunogenicity of Pneumococcal Vaccine in HIV Patients with Toll-like Receptor Agonist Adjuvant
Abstract & Commentary
By Dean L. Winslow, MD, FACP, FIDSA, Chief, Division of AIDS Medicine, Santa Clara Valley, Medical Center; Clinical Professor, Stanford University School of Medicine, is Associate Editor for Infectious Disease Alert.
Synopsis: CPG 7909 is a toll-like receptor 9 (TLR9) agonist and vaccine adjuvant. In a randomized, double-blind, placebo-controlled trial, CPG 7909 was studied in combination with 7-valent pneumococcal conjugate vaccine (PCV7) given at 0 and 3 months and 23-valent pneumococcal polysaccharide vaccine (PPV23) given at 9 months; 97 patients were studied. The addition of CPG 7909 significantly enhanced the proportion of vaccine-high responders.
Source: Segaard OS, et al. Improving the immunogenicity of pneumococcal conjugate vaccine in HIV-infected adults with a toll-like receptor 9 agonist adjuvant: A randomized, controlled trial. Clin Infect Dis. 2010;51:42-50.
CPG 7909 1 mg added to vaccine was studied in a randomized, double-blind, placebo-controlled trial in combination with PCV7 given at time 0 and 3 months and PPV23 given at nine months in a trial with 97 HIV-infected adult patients. (Control patients received phosphate-buffered saline.) The primary endpoint was the proportion of vaccine-high responders at nine months (as defined as a two-fold increase in IgG levels to >= 1 ug/mL for at least five of the seven PCV7 pneumococcal capsular serotypes). The proportion of vaccine-high responders at nine months in the treatment group was 48.8% vs. 25% in the control group. The proportion of high responders also was greater at all other time points (51.1% vs. 39.6% at three months, 77.3% vs. 56.3% at four months, 87.8% vs. 51.1% at 10 months). Mild systemic and injection-site reactions were more common in the adjuvant group than in the control group (100% vs. 81.3%). No adverse effects on CD4+ cell count or organ dysfunction occurred in either group.
Commentary
High rates of invasive pneumococcal disease occur in HIV-infected patients despite effective HAART, and are a major cause of morbidity and mortality in HIV-infected patients at all CD4+ strata. PPV23 has limited efficacy in HIV-negative older adults,1-3 and even less efficacy in HIV-infected adults and children. While PCV7 has been very effective in preventing invasive pneumococcal disease in HIV-negative pediatric patients, a single injection of PCV7 has not been shown to be superior to PPV23 in HIV-infected adults.4-6
This study presents some good news for HIV-infected patients. While the trial excluded patients with CD4+ < 200 cells/uL, this study of largely HAART-treated patients (with median CD4+ count 673 and 605 in the adjuvant and control groups respectively) is representative of the majority of HIV-infected patients in many of our practices today. This TLR9 adjuvant represents some nice translational research that appears close to being available to help patients.
References
- Johnstone J, et al. Impact of the pneumococcal vaccine on long-term morbidity and mortality of adults at high risk for pneumonia. Clin Infect Dis. 2010;51:15-22.
- Moberly S, et al. Vaccines for preventing pneumococcal infection in adults. Cochrane Database Syst Rev. 2008: CD000422.
- Huss A, et al. Efficacy of pneumococcal vaccination in adults: a meta-analysis. CMAJ. 2009;180:48-58.
- Rodriguez-Barradas MC, et al. Response of human immunodeficiency virus-infected patients receiving highly active antiretroviral therapy to vaccination with 23-valent pneumococcal polysaccharide vaccine. Clin Infect Dis. 2003;37:438-447.
- Kroon FP, et al. Enhanced antibody response to pneumococcal polysaccharide vaccine after prior immunization with conjugate pneumococcal vaccine in HIV-infected adults. Vaccine. 2000;19:886-894.
- Feikin DR, et al. Specificity of the antibody response to the pneumococcal polysaccharide and conjugate vaccines in human immunodeficiency virus-infected adults. Clin Diagn Lab Immunol. 2004;11:137-141.
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