Long-term Immunogenicity of the HIV gp120-NefTat/AS01B Vaccine (GSK SB732461)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the long-term persistence of binding antibody responses against V1V2 and gp120 in subjects who were vaccinated with the envelope glycoprotein 120 (gp120)-negative factor (Nef)Tat/ Adjuvant System 01B (AS01B) (GSKSB732461) vaccine candidate. Other immune parameters like the HIV-specific cluster of differentiation (CD4+) T cell and CD8+ T cell responses will also be evaluated.

Detailed Description
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GlaxoSmithKline (GSK) contributes to the public-private pox-protein partnership (P5) which is currently assessing the safety, immunogenicity and clinical efficacy of a prime-boost regimen aimed at preventing HIV transmission (http://www.hvtn.org/en.html). The booster component of the candidate vaccine used in this program consists of two gp120 clade C proteins administered with an adjuvant. In order to inform the selection of the adjuvant in future studies, data on long-term persistence of immunity after vaccination with gp120/AS01 would prove useful. The present study was designed to address this question using a cohort of volunteers vaccinated several years ago with a candidate vaccine containing gp120 and AS01.

Official Title
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Long-term Immunogenicity of the HIV gp120-NefTat/AS01B Vaccine (GSK SB732461)

Conditions
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Infection, Human Immunodeficiency Virus, HIV Infections

Intervention / Treatment
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* Procedure: Blood sampling


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who, in the opinion of the investigator, can and will comply with the requirements of the protocol. Written informed consent obtained from the subject prior to performing any study specific procedure. A subject who has received at least 3 doses of the gp120-NefTat/AS01B (GSKSB732461) vaccine candidate in GSK Biologicals-sponsored PRO HIV-002 study. Exclusion Criteria: Use of any investigational or non-registered product during 30 days prior to study enrolment. History of HIV-1 or HIV-2 infection. Participation to another clinical trial of an investigational HIV vaccine between study PRO HIV-002 and the present study. Chronic administration of immunosuppressants or other immune-modifying drugs during the period starting one month preceding this study. For corticosteroids, this will mean prednisone higher than or equal to (≥) 20 mg/day . Inhaled and topical steroids are allowed. Administration of cytotoxic medication within 6 months preceding this study. History of daily, long-term immunosuppressive medication between study PRO HIV-002 and the present study. Administration of immunoglobulins and/or any blood products during the period starting 3 months before enrolment. Any confirmed or suspected immunosuppressive or immunodeficient condition other than HIV disease, based on medical history and physical examination between study PRO HIV-002 and the present study. Past administration of an investigational vaccine containing AS01 other than the gp120-NefTat/AS01B (GSKSB732461) vaccine administered in PRO HIV-002 study.

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Interventional Model Description: Descriptive mono-centric study with one single group.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GSKSB732461 Group<br>Healthy HIV uninfected volunteers who participated in study PRO HIV-002 between February 2003 and February 2005 and who were vaccinated with at least 3 doses of the GSKSB732461 vaccine candidate in the PRO-HIV-002 study. | Procedure: Blood sampling<br>* Blood samples will be taken during the single study visit at Year 14 for the assessment of: HIV testing, antibody determination, cell mediated immune (CMI) responses and exploratory characterisation.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Anti-V1V2 Total Immunoglobulin G (IgG) Binding Antibody Multiplex Assay (BAMA) Response Call | To comply with BAMA methodology and terminology, the wording BAMA response call status was used instead of seropositivity in the analysis. Compared to baseline result (Day 0), a sample is called positive for a given analyte if the response magnitude is equal to or above (≥) the analyte specific cutoff from all baseline samples in the study (where the cutoff is the 95th percentile of the baseline response, or 100, whichever is higher) OR ≥3 times the response magnitude as compared to the sample specific baseline. The C.1086C_V1_V2 Tags strain was not part of any breadth panel. Due to low or infrequent response, or undetectable levels of response among the breadth panel strains, some additional strains, not part of the breadth panels, were also analyzed. | At Day 182, Day 672 historical time points of PRO-HIV-002 and at Year 14 | 
| Anti-V1V2 Total IgG Antibody BAMA Response Magnitude | Whenever results were provided as Mean Fluorescence Intensity (MFI), the statistical outputs BAMA response magnitude (MFI) terminology is used instead of concentrations/titres. The C.1086C_V1_V2 Tags strain was not part of any breadth panel. Due to low or infrequent response, or undetectable levels of response among the breadth panel strains, some additional strains, not part of the breadth panels, were also analyzed. | At Day 0, Day 182, Day 672 historical time points of PRO-HIV-002 and at Year 14 | 
| Number of Subjects With Anti-V1V2 Subtypes Range: IgG1, IgG2, IgG3 and IgG4 Response Call | To comply with BAMA methodology and terminology, the wording BAMA response call status was used instead of seropositivity in the analysis. Compared to baseline result (Day 0), a sample is called positive for a given analyte if the response magnitude is equal to or above (≥) the analyte specific cutoff from all baseline samples in the study (where the cutoff is the 95th percentile of the baseline response, or 100, whichever is higher) OR ≥3 times the response magnitude as compared to the sample specific baseline. Antigen IgG3 was assessed for all strains. Antigens IgG1, IgG2 and IgG4 were assessed only for C.1086C_V1_V2 Tags strain that was not part of any breadth panel. Due to low or infrequent response, or undetectable levels of response among the breadth panel strains, some additional strains, not part of the breadth panels, were also analyzed. | At Day 182, Day 672 historical time point of PRO-HIV-002 and at Year 14 | 
| Anti-V1V2 IgG1, IgG2, IgG3 and IgG4 Antibody BAMA Response Magnitude | Whenever results were provided as Mean Fluorescence Intensity (MFI), the statistical outputs BAMA response magnitude (MFI) terminology is used instead of concentrations/titres. Antigen IgG3 was assessed for all strains. Antigens IgG1, IgG2 and IgG4 were assessed only for C.1086C_V1_V2 Tags strain that was not part of any breadth panel. Due to low or infrequent response, or undetectable levels of response among the breadth panel strains, some additional strains, not part of the breadth panels, were also analyzed. | At Day 0, Day 182, Day 672 historical time points of PRO-HIV-002 and at Year 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Anti-envelope Glycoprotein (Anti-gp) 120 Total IgG BAMA Response Call | To comply with BAMA methodology and terminology, the wording BAMA response call status was used instead of seropositivity in the analysis. Compared to baseline result (Day 0), a sample is called positive for a given analyte if the response magnitude is equal to or above (≥) the analyte specific cutoff from all baseline samples in the study (where the cutoff is the 95th percentile of the baseline response, or 100, whichever is higher) OR ≥3 times the response magnitude as compared to the sample specific baseline. The strains: 086C_D7gp120.avi/293F IgG, Con 6 gp120/B IgG, and gp120 (Clone W6.1D) IgG were not part of any breadth panel. Due to low or infrequent response, or undetectable levels of response among the breadth panel strains, some additional strains, not part of the breadth panels, were also analyzed. | At Day 182, Day 672 historical time points of PRO-HIV-002 and at Year 14 | 
| Anti-gp 120 Total IgG Antibody BAMA Response Magnitude | Whenever results were provided as Mean Fluorescence Intensity (MFI), the statistical outputs BAMA response magnitude (MFI) terminology is used instead of concentrations/titres. The strains: 086C_D7gp120.avi/293F IgG, Con 6 gp120/B IgG, and gp120 (Clone W6.1D) IgG were not part of any breadth panel. Due to low or infrequent response, or undetectable levels of response among the breadth panel strains, some additional strains, not part of the breadth panels, were also analyzed. | At Day 0, Day 182, Day 672 historical time points of PRO-HIV-002 and at Year 14 | 
| Number of Subjects With Anti-gp120 (IgG1, IgG2, IgG3 and IgG4) BAMA Response Call for Analytes Not Part of Any Breadth Panel | To comply with BAMA methodology and terminology, the wording BAMA response call status was used instead of seropositivity in the analysis. Compared to baseline result (Day 0), a sample is called positive for a given analyte if the response magnitude is equal to or above (≥) the analyte specific cutoff from all baseline samples in the study (where the cutoff is the 95th percentile of the baseline response, or 100, whichever is higher) OR ≥3 times the response magnitude as compared to the sample specific baseline.Analysis was performed on the gp120 antigen (IgG1, IgG2, IgG3 and IgG4) for the following vaccine HIV strains which were not part of any breadth panel: 1086C_D7gp120.avi/293F IgG, Con 6 gp120/B IgG, and gp120 (Clone W6.1D) IgG. Due to low or infrequent response, or undetectable levels of response among the breadth panel strains, some additional strains, not part of the breadth panels, were also analyzed. | At Day 182, Day 672 historical time points of PRO-HIV-002 and at Year 14 | 
| Anti-gp120 (IgG1, IgG2, IgG3 and IgG4) BAMA Response Magnitude for Analytes Not Part of Any Breadth Panel | Whenever results were provided as Mean Fluorescence Intensity (MFI), the statistical outputs BAMA response magnitude (MFI) terminology is used instead of concentrations/titres. Analysis was performed on the gp120 antigen (IgG1, IgG2, IgG3 and IgG4) for the following vaccine HIV strains: which were not part of any breadth panel: 1086C_D7gp120.avi/293F IgG, Con 6 gp120/B IgG, and gp120 (Clone W6.1D) IgG. Due to low or infrequent response, or undetectable levels of response among the breadth panel strains, some additional strains, not part of the breadth panels, were also analyzed. | At Day 0, Day 182, Day 672 historical time points of PRO-HIV-002 and at Year 14 | 
| Frequency of Human Immunodeficiency Virus Type 1 (HIV-1) Specific Cluster of Differentiation-4 (CD4+) T Cells Expressing at Least 2 Cytokine Markers | Assessed cytokines include: cluster of differentiation-40 lingand (CD40-L), Interleukin-2 (IL2), Tumour Necrosis Factor-alpha (TNF-α), Interferon-gamma (INF-γ), by Intracellular Cytokine Staining (ICS). CD4+ T-cells were expressed in CD4+ T-cells/million cells. | At Day 0, Day 98, Day 672 historical time points of PRO-HIV-002 and at Year 14 | 
| Number of Vaccine Responders for HIV-1-specific CD4+ T-cells Expressing at Least 2 Cytokine Markers | Vaccine response rates for HIV-1-specific CD4+ T cells expressing at least two markers among CD40L, IL-2, TNF-α and IFN-γ with responders were defined as subjects with: a 2-fold increase as compared to the cut-off (=354, limit of quantification [LOQ] of the assay), for subjects with pre-vaccination frequency below the cut-off, at Day 0, OR at least 2-fold increase as compared to pre-vaccination frequency, for subjects with pre-vaccination frequency above the cut-off. | At Day 98 and at Day 672 historical time points of PRO-HIV-002 and at Year 14 | 
| Frequency of Human Immunodeficiency Virus Type 1 (HIV-1) Specific CD8+ T-cells Expressing at Least 2 Cytokine Markers | Assessed cytokines include: CD40-L, IL2, TNF-α, INF-γ, by ICS. CD8+ T-cells were expressed in CD8+ T-cells/million cells/million cells. | At Day 0, Day 98, Day 672 historical time points of PRO-HIV-002 and at Year 14 | 
| Number of Vaccine Responders for HIV-1-specific CD8+ T-cells Expressing at Least 2 Cytokine Markers | Vaccine response rates for HIV-1-specific CD8+ T cells expressing at least two markers among CD40L, IL-2, TNF-α and IFN-γ with responders were defined as subjects with: a 2-fold increase as compared to the cut-off (=354, limit of quantification [LOQ] of the assay), for subjects with pre-vaccination frequency below the cut-off, at Day 0, OR at least 2-fold increase as compared to pre- vaccination frequency, for subjects with pre-vaccination frequency above the cut-off. | At Day 98, Day 672 historical time points of PRO-HIV-002 and at Year 14 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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gp120, HIV infections, RV144, gp120-NefTat/AS01B vaccine candidate, V1V2