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

Study Description

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
HIV Infections	Biological: Pneumococcal vaccines + CPG 7909; Biological: Pneumococcal vaccines	Phase 1; Phase 2

Detailed Description:

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

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	97 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Prevention
Official Title:	Immune Response to Toll-Like Receptor 9-Agonist Adjuvanted Pneumococcal Vaccination in HIV Infected Adults
Study Start Date :	January 2008
Actual Primary Completion Date :	January 2009
Actual Study Completion Date :	January 2009

Arms and Interventions

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm	Intervention/treatment
Experimental: A; 1 mg CpG 7909 + pneumococcal vaccines	Biological: Pneumococcal vaccines + CPG 7909; 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; Other Name: Cpg 7909/Vaximmune(TM)
Placebo Comparator: B; Pneumococcal vaccines	Biological: Pneumococcal vaccines; 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

Outcome Measures

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Primary Outcome Measures :

1. 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 [ Time Frame: At day 270 ]

Secondary Outcome Measures :

1. Functional activity of anticapsular antibodies measured by OPA [ Time Frame: At day 90, 120, 270, 300 ]
2. Safety/Tolerability [ Time Frame: During the entire trial period ]
3. Nasopharyngeal pneumococcal colonization [ Time Frame: At day 270 ]
4. Predictors of antibody response, i.e. CD4+ cell count and sCD163 [ Time Frame: At baseline ]
5. 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 [ Time Frame: At day 90,120 and 300 ]
6. Quantity and differentiation of IgG subtypes for HAART-experienced and HAART-naive individuals [ Time Frame: Day 0, 90, 120 ]
7. Cytokine response to various antigens by in vitro cell stimulation for HAART-experienced and HAART-naive individuals [ Time Frame: At day 0, 90, 120 ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

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Locations

Denmark
Department of Infectious Diseases, Aarhus University Hospital
Aarhus, Denmark, 8200

Sponsors and Collaborators

University of Aarhus

Aarhus University Hospital

Investigators

Principal Investigator:	Ole Sogaard, MD	Department of Infectious Diseases, Aarhus University Hospital, Denmark
Study Director:	Lars Ostergaard, MD,PhD,DmSC	Department of Infectious Diseases, Aarhus University Hospital, Denmark

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Offersen R, Melchjorsen J, Paludan SR, Østergaard L, Tolstrup M, Søgaard OS. TLR9-adjuvanted pneumococcal conjugate vaccine induces antibody-independent memory responses in HIV-infected adults. Hum Vaccin Immunother. 2012 Aug;8(8):1042-7. doi: 10.4161/hv.20707. Epub 2012 Aug 1.

Søgaard OS, Lohse N, Harboe ZB, Offersen R, Bukh AR, Davis HL, Schønheyder HC, Østergaard L. 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 Jul 1;51(1):42-50. doi: 10.1086/653112.

Responsible Party:	Ole Søgaard, MD, Department of Infectious Diseases, Skejby
ClinicalTrials.gov Identifier:	NCT00562939 History of Changes
Other Study ID Numbers:	2007-001588-31
First Posted:	November 26, 2007
Last Update Posted:	January 21, 2009
Last Verified:	January 2009

Keywords provided by University of Aarhus:

Antibody Formation; Antibody Affinity; Immunity; Pneumococcal Vaccines; Oligodeoxyribonucleotides

Additional relevant MeSH terms:

HIV Infections; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases	Immunologic Deficiency Syndromes; Immune System Diseases; Vaccines; Antibodies; Heptavalent Pneumococcal Conjugate Vaccine; Immunologic Factors; Physiological Effects of Drugs