Clinical trial NCT00562939: Immune Response to Toll-Like Receptor 9-Agonist Adjuvanted Pneumococcal Vaccination in HIV Infected Adults
Official title: Immune Response to Toll-Like Receptor 9-Agonist Adjuvanted Pneumococcal Vaccination in HIV Infected Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: HIV Infections
Keywords: Antibody Formation
Antibody Affinity
Immunity
Pneumococcal Vaccines
Oligodeoxyribonucleotides
Lead sponsor: University of Aarhus
Sponsor class: OTHER
Collaborators: name: Aarhus University Hospital
First posted: 2007-11-26
Enrollment: 97
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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

Eligibility 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

Primary outcomes:
measure: 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
timeFrame: At day 270
Secondary outcomes:
measure: Functional activity of anticapsular antibodies measured by OPA
timeFrame: At day 90, 120, 270, 300
measure: Safety/Tolerability
timeFrame: During the entire trial period
measure: Nasopharyngeal pneumococcal colonization
timeFrame: At day 270
measure: Predictors of antibody response, i.e. CD4+ cell count and sCD163
timeFrame: At baseline
measure: 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
timeFrame: At day 90,120 and 300
measure: Quantity and differentiation of IgG subtypes for HAART-experienced and HAART-naive individuals
timeFrame: Day 0, 90, 120
measure: Cytokine response to various antigens by in vitro cell stimulation for HAART-experienced and HAART-naive individuals
timeFrame: At day 0, 90, 120
Other outcomes:
Locations:
city: Aarhus
country: Denmark
facility: Department of Infectious Diseases, Aarhus University Hospital
Study officials:
affiliation: Department of Infectious Diseases, Aarhus University Hospital, Denmark
name: Ole Sogaard, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Infectious Diseases, Aarhus University Hospital, Denmark
name: Lars Ostergaard, MD,PhD,DmSC
role: STUDY_DIRECTOR
References:
citation: Offersen R, Melchjorsen J, Paludan SR, Ostergaard L, Tolstrup M, Sogaard 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.
citation: Sogaard OS, Lohse N, Harboe ZB, Offersen R, Bukh AR, Davis HL, Schonheyder HC, Ostergaard 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.