Immune Response to Toll-Like Receptor 9-Agonist Adjuvanted Pneumococcal Vaccination in HIV Infected Adults

Study Overview
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Brief Summary
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The purpose of this study is to determine whether TLR-9 adjuvanted pneumococcal is more immunogenic than pneumococcal vaccination alone in HIV-infected adults.

Detailed Description
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Pneumococcal disease is a major source of morbidity and mortality in HIV-patients. HIV-patients are vaccine hyporesponders. A good immune response to pneumococcal vaccination enhances vaccine effectiveness, thereby preventing the morbidity and mortality caused by pneumococcal disease. Even when an optimized regimen containing both conjugated and polysaccharide pneumococcal vaccine is used, only 13% of the immunized HIV patients are high responders at week 96. Recent data indicate that TLR9-agonists have excellent vaccine adjuvant potential and are safe to use in immunocompetent as well as immunocompromised individuals. The aim of this study is to evaluate the qualitative and quantitive immune response to pneumococcal vaccination with or without TLR9-agonist in HIV-infected adults

Official Title
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Immune Response to Toll-Like Receptor 9-Agonist Adjuvanted Pneumococcal Vaccination in HIV Infected Adults

Conditions
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HIV Infections

Intervention / Treatment
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* Biological: Pneumococcal vaccines + CPG 7909
* Biological: Pneumococcal vaccines


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent and authority statement provided according to local regulatory and ethical practice using a participant information sheet and informed consent form approved by the responsible Ethics Committee. HIV-seropositive individuals. Exclusion Criteria: Pregnancy as determined by a positive urine beta-hCG (if female) Participant unwilling to use reliable contraception methods for the duration of the trial. Reliable methods of birth control include: pharmacologic contraceptives including oral, parenteral, and transcutaneous delivery; condoms with spermicide; diaphragm with spermicide; surgical sterilization; vaginal ring; intrauterine device; abstinence; and post-menopause (if female) Currently breast-feeding (if female) Latest CD4 count < 200 x106 cells/µL Viral load (HIV RNA) > 50 copies/mL if on HAART (defined as at least three antiretrovirals including either a protease inhibitor or a NNRTI, i.e. combivir 300/150 mg x2 + stocrin 600 mg x1 for a minimum of 6 months) Previous enrollment in this study Any medical, psychiatric, social, or occupational condition or other responsibility that, in the judgment of the Principal Investigator (PI), would interfere with the evaluation of study objectives (such as severe alcohol abuse, severe drug abuse, dementia) Unable to follow protocol regimen Pneumococcal vaccination 5 years or less prior to inclusion Planned participation in other vaccination trials during the time of the study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>1 mg CpG 7909 + pneumococcal vaccines | Biological: Pneumococcal vaccines + CPG 7909<br>* Day 0: 1 ml Prevenar (double dose) + 1 mg CpG 7909, IM Day 90: 1 ml Prevenar (double dose) + 1 mg CpG 7909, IM Day 270: 0.5 ml Pneumo Novum + 1 mg CpG 7909, IM<br>* Other names: Cpg 7909/Vaximmune(TM);|
| Placebo Comparator: B<br>Pneumococcal vaccines | Biological: Pneumococcal vaccines<br>* Day 0: 1 ml Prevenar (double dose) + placebo, IM Day 90: 1 ml Prevenar (double dose) + placebo, IM Day 270: 0.5 ml Pneumo Novum + placebo, IM<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Numbers of vaccine high responders - defined as 2-fold increase and IgG levels ≥1 µg/mL to at least 5 of 7 pneumococcal serotypes (by quantitative IgG measurements) - in the CpG 7909 group vs. the control group |  | At day 270 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Functional activity of anticapsular antibodies measured by OPA |  | At day 90, 120, 270, 300 | 
| Safety/Tolerability |  | During the entire trial period | 
| Nasopharyngeal pneumococcal colonization |  | At day 270 | 
| Predictors of antibody response, i.e. CD4+ cell count and sCD163 |  | At baseline | 
| Numbers of vaccine high responders - defined as 2-fold increase and IgG levels ≥1 µg/mL to at least 5 of 7 pneumococcal serotypes (by quantitative IgG measurements) - in the CpG 7909 group vs. the control group |  | At day 90,120 and 300 | 
| Quantity and differentiation of IgG subtypes for HAART-experienced and HAART-naive individuals |  | Day 0, 90, 120 | 
| Cytokine response to various antigens by in vitro cell stimulation for HAART-experienced and HAART-naive individuals |  | At day 0, 90, 120 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Antibody Formation, Antibody Affinity, Immunity, Pneumococcal Vaccines, Oligodeoxyribonucleotides