Placebo and vaccines were administered intramuscularly into the deltoid muscle of the non-dominant upper arm.

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1 The study listed may include approved and non-approved uses, formulations or treatment regimens. The results reported in any single study may not reflect the overall results obtained on studies of a product. Before prescribing any product mentioned in this Register, healthcare professionals should consult prescribing information for the product approved in their country. GSK Medicine: GSK A (GlaxoSmithKline [GSK] Biologicals investigational adjuvanted vaccine against Hepatitis B) Study Number: (EARLY-CLINRES-008) Title: Development of read-outs to detect and characterise the early and adaptive immune responses in healthy, hepatitis B virus naive adults vaccinated with the hepatitis B surface antigen in combination with a GSK Biologicals Adjuvant System. Rationale: The main purpose of this clinical trial is to develop new read-outs aimed at detecting and characterising the early immune response and its kinetics within the first days after vaccination as well as the adaptive immune response to the hepatitis B surface antigen (used as model antigen) in combination with a GSK Biologicals Adjuvant System or with aluminium hydroxide (Engerix -B). The immunogenicity and safety of the two vaccine formulations are to be evaluated up to 6 months post last study vaccine administration: HBsAg/AS - GSK Biologicals investigational adjuvanted Hepatitis B formulation Engerix -B (HBsAg/Alum) - GSK Biologicals Hepatitis B vaccine adjuvanted with aluminium hydroxide. Phase: II Study Period: From 25-Feb-13 to 05-Aug-2014 (end of Step 1) 13-Sept-2016 (end of Step 2) Study Design: Randomised, single-blind (in Step 1) and open-label (in Step 2), single centre controlled study in 2 Steps. The duration of the study for each subject enrolled in Step 1 was approximately 240 days from placebo administration. In Step 2, the duration of the study for each subject enrolled in the group receiving HBsAg/AS was approximately 180 days from Dose 1 administration and approximately 330 days from Dose 1 administration for each subject enrolled in the group receiving HBsAg/Alum. Centres: 1 Centre in Belgium. Indication: Hepatitis B surface antigen (HBsAg) vaccine administered in hepatitis B virus (HBV) naive adult subjects aged between 18 and 45 years old, inclusive, in good general health. Treatment: In Step 1, the study groups were as follows: -S1AS Group: ~30 subjects aged years, who received 1 dose of Placebo at Day -30 followed by 2 doses of HBsAg/AS, at Day 0 and Day 30 -S1Alum Group: ~30 subjects aged years, who received 1 dose of Placebo at Day -30 followed by 3 doses of HBsAg/Alum at Day 0, Day 30 and Day 180. In this step, a sub-cohort of ~30 subjects (~15 in each group) was asked to stay overnight at the study centre to allow collection of blood for the evaluation of immunogenicity and to evaluate reactogenicity and safety 18 hours post study product administration. In Step 2, the study groups were as follows: -S2AS Group: ~15 subjects aged years, receiving 2 doses of HBsAg/AS, at Day 0 and Day 30 -S2Alum Group: ~15 subjects aged years, receiving 3 doses of HBsAg/Alum at Day 0, Day 30 and Day 180. Placebo and vaccines were administered intramuscularly into the deltoid muscle of the non-dominant upper arm. Note: For each parameter analysed in both Step 1 and Step 2, subjects were pooled into S1AS+S2AS Group and S1Alum+ S2Alum Group. Pooling steps also occurred for safety analyses. Objectives: To detect and measure soluble mediators from the early immune response in plasma. Primary Outcome/Efficacy Variable: Innate/early immune response: Soluble mediators from the innate/early immune response at protocol-defined time-points in all subjects (Step 1 and Step 2): Cytokines and chemokines in plasma: Concentration of cytokines and chemokines (e.g. Interleukin (IL)-6, Interferon Gamma (IFN)-γ, Macrophage Inflammatory Protein (MIP-1α), IL-8), as measured by Multiplex. Secondary Outcome/Efficacy Variable(s): Adaptive response: Classical cellular and humoral immune response to components of the study vaccine at protocol-defined time-points:

2 Anti-HBs IgG antibody concentrations in serum, as measured by Chemi Luminescence Immuno Assay (CLIA) (Step 1 and Step 2). Frequency of HBs-specific Cluster of Differentiation (CD)4+/CD8+ T-cells expressing at least 2 immune markers among IL-2, IFN-γ, Tumor Necrosis Factor (TNF)-α, CD40L, as measured by classical (qualified assay) Intracellular Cytokine Staining (ICS), using frozen Peripheral blood mononuclear cells (PBMCs) (Step 1 only). Occurrence of solicited and non-serious unsolicited adverse events (AEs) post first 3 study product administration in Step 1 and after each vaccine administration in Step 2: Occurrence of each solicited local and general AE as assessed by the subject during a 7-day follow-up period (i.e. day of vaccination and 6 subsequent days). Recording of injection site pain (using a numerical rating scale [NRS]), recording of body temperature, and measurement of injection site redness and swelling as assessed by the investigator/study nurse up to 4 days post-placebo/vaccine administration (i.e. throughout the day of vaccination and at the 3 subsequent days) in Step 1. Recording of injection site pain (using a numerical rating scale [NRS]), recording of body temperature, and measurement of injection site redness and swelling as assessed by the investigator/study nurse during a 3-day follow-up period (i.e. throughout the day of vaccination and at the 2 subsequent days) post Dose 2/Dose 3 administration in the S2AS/S2Alum groups in Step 2. Occurrence of any unsolicited AE during a 28-day follow-up period (i.e. day of vaccination and 27 subsequent days). Occurrence of any serious adverse event (SAE) occurring from first placebo/vaccine administration up to study conclusion of each step. Occurrence of any Potential Immune-Mediated Disease (pimd) occurring from first placebo/vaccine administration up to study conclusion of each step. Occurrence of any new medical condition requiring medical attention occurring from first placebo/vaccine administration up to study conclusion of each step. Safety laboratory parameters at protocol defined time-points. Haematological (Red Blood Cell (RBC), White Blood Cell (WBC) and differential count, platelets count and haemoglobin) and biochemical (Alanine aminotransferase [ALT], Aspartate aminotransferase [AST], total bilirubin, serum creatinine, urea, Lactate dehydrogenase [LDH], Creatinine phosphokinase [CPK] and c-reactive protein [CRP]) levels in Step 1. Haematological (WBC and differential count and platelets count) and biochemical (ALT, AST, total bilirubin and CRP) levels in Step 2. Vital signs at protocol defined time-points. Systolic/diastolic blood pressure. Heart rate. Respiratory rate. Statistical Methods: Analyses were performed on the Total Vaccinated cohort, the According-To-Protocol (ATP) cohort for innate immunogenicity up to Day 60, the ATP cohort for adaptive immunogenicity up to Day 60, the ATP cohort for innate immunogenicity up to 30 days post last vaccination, the ATP cohort for adaptive immunogenicity up to 30 days post last vaccination and the ATP cohort for persistence: The Total Vaccinated cohort included all subjects with at least one vaccine administration documented. The ATP cohort for innate immunogenicity up to Day 60 (step 1 only) included all evaluable subjects (i.e. those who met all eligibility criteria, who received at least one dose of study vaccine according to their random assignment, who had not received a vaccine not specified or forbidden in the protocol), who complied with the procedures and intervals defined in the protocol and for whom data concerning innate immunogenicity were available for at least one innate assay at one post-vaccination time point (up to Day 60). The ATP cohort for adaptive immunogenicity up to Day 60 (step 1 only) included all evaluable subjects (i.e. those who met all eligibility criteria, who received at least one dose of study vaccine according to their random assignment, who had not received a vaccine not specified or forbidden in the protocol), who complied with the procedures and intervals defined in the protocol and for whom data concerning adaptive immunogenicity were available for at least one adaptive assay at one post-vaccination time point (up to Day 60). The ATP cohort for innate immunogenicity up to 30 days post last vaccination (step 2 only) included all evaluable subjects (i.e. those who met all eligibility criteria, who received at least one dose of study vaccine according to their random assignment, who had not received a vaccine not specified or forbidden in the protocol), who complied with the procedures and intervals defined in the protocol, with no elimination criteria during the study (up to Day 60 for the S2AS group and up to Day 210 for the S2Alum Group) for whom data concerning innate immunogenicity were

3 available for at least one innate assay at one post-vaccination time point (up to Day 60 for the S2AS group and up to Day 210 for the S2Alum Group). The ATP cohort for adaptive immunogenicity up to 30 days (step 2 only) post last vaccination included all evaluable subjects (i.e. those who met all eligibility criteria, who received at least one dose of study vaccine according to their random assignment, who had not received a vaccine not specified or forbidden in the protocol), who complied with the procedures and intervals defined in the protocol, with no elimination criteria during the study (up to Day 60 for the S2AS group and up to Day 210 for the S2Alum Group) for whom data concerning adaptive immunogenicity were available for at least one adaptive assay at one post-vaccination time point (up to Day 60 for the S2AS group and up to Day 210 for the S2Alum Group). The ATP cohort for persistence (step 1 only) included all subjects from the ATP cohort for analysis of adaptive immunogenicity who complied with the procedures and intervals defined in the protocol, with no elimination criteria during the study and for whom data concerning adaptive immunogenicity were available for at least one adaptive assay at Day 180. The ATP cohort for persistence (step 2 only) included all evaluable subjects (i.e. those who met all eligibility criteria, who received at least one dose of study vaccine according to their random assignment, who had not received a vaccine not specified or forbidden in the protocol), with no elimination criteria during the study, for whom data concerning adaptive immunogenicity were available for at least one adaptive assay at Day 180 for the S2AS Group and at Day 330 for the S2Alum Group. Analysis of Immunogenicity: For each study vaccine group in both steps, at each blood sampling time point for which results are available, descriptive statistics (N, Q1, median, Q3) of cytokine and chemokine concentrations in plasma were tabulated. For each study vaccine group in both steps, at each blood sampling time point for which anti-hbs IgG antibody concentrations are available, seropositivity rates, seroprotection rates and GMCs were tabulated with their 95% CIs. In step 1, for each study vaccine group, at each blood sampling time point for which HBs-specific CD4 + /CD8 + T-cells frequencies (by classical ICS using PBMCs) were available, descriptive statistics (N, Q1, median, Q3) were tabulated (data expressed in cells per million cells). Validated method was used, meaning that the replacement of negative and zero values was done after addition of the 11 combinations separately for the background and the HBs stimulation. The background value was then subtracted from the HBs stimulation. Analysis of Safety (solicited and unsolicited adverse events) For each study vaccine group, the following parameters were tabulated for step 1, step 2 and pooling steps: the percentage of subjects reporting each individual solicited local and general AE during the 7-day (Days 0-6) postplacebo/vaccine administration (after each dose and across doses) with exact 95% CI. The same tabulation was performed for grade 3 symptoms and for general symptoms assessed by the investigators as related to vaccination. the percentage of subjects with unsolicited AEs reported during the 28-day (Days 0-27) post-placebo/vaccine administration, as well as the summary of solicited and unsolicited AEs experienced by at least 5 % of subjects within the 28-day (Days 0-27) post-vaccination period including number of events - SAE excluded and classified according to the Medical Dictionary for Regulatory Activities (MedDRA) preferred terms. the percentage of subjects with pimds and the percentage of subjects with new medical condition requiring medical attention, reported from first placebo/vaccine administration up to study end. the percentage of subjects with SAEs and SAEs assessed by the investigator as related to the vaccination, reported up to study end. In addition, recording of injection site pain (using a numerical rating scale [NRS]), recording of body temperature, and measurement of injection site redness and swelling as assessed by the investigator/study nurse up to 4 days postplacebo/vaccine administration was tabulated by study vaccine group for step 1 and up to 3-days post-vaccine administration for step 2 and pooling steps (except for temperature). Descriptive statistics (N, Q1, median, Q3) of haematological and biochemical parameters and of vital signs assessed at different time points up to study end were tabulated per study vaccine group for step 1 and step 2. Study Population: Healthy male or female subjects between, and including, 18 and 45 years of age at the time of placebo (Step 1)/ first vaccine dose (Step 2) administration. Female subjects were to be of non-childbearing potential or if of childbearing potential, had to practice adequate contraception for 30 days prior to placebo (Step 1)/ first vaccine dose (Step 2) administration, to have a negative pregnancy test on the day of placebo administration/ vaccination, and were to continue such precautions during the entire treatment period and for 2 months after completion of the study. Subjects should not have any previous administration of vaccine components nor received any previous vaccination against Hepatitis B. Written informed consent was obtained from all subjects prior to enrolment in the study. Number of subjects vaccinated, completed and withdrawn with reason for withdrawal (Total Vaccinated cohort)

4 Step 1 S1AS Group S1Alum Group Total Group Number of subjects vaccinated Number of subjects completed Number of subjects withdrawn Reasons for withdrawal : Serious Adverse Event Non-Serious Adverse Event Protocol violation Consent withdrawal (not due to an adverse event) Migrated/moved from study area Lost to follow-up (subjects with incomplete vaccination course) Lost to follow-up (subjects with complete vaccination course) Sponsor study termination Others Step 2 S2AS Group S2Alum Group Total Group Number of subjects vaccinated Number of subjects completed Number of subjects withdrawn Reasons for withdrawal : Serious Adverse Event Non-Serious Adverse Event Protocol violation Consent withdrawal (not due to an adverse event) Migrated/moved from study area Lost to follow-up (subjects with incomplete vaccination course) Lost to follow-up (subjects with complete vaccination course) Sponsor study termination Others Pooling Steps S1AS+S2AS S1Alum+ Total Group Group S2Alum Group Number of subjects vaccinated Number of subjects completed Number of subjects withdrawn Reasons for withdrawal : Serious Adverse Event Non-Serious Adverse Event Protocol violation Consent withdrawal (not due to an adverse event) Migrated/moved from study area Lost to follow-up (subjects with incomplete vaccination course) Lost to follow-up (subjects with complete vaccination course) Sponsor study termination Others Vaccinated = number of subjects who were vaccinated in the study Completed = number of subjects who completed last study visit With Withdrawn = number of subjects who did not come back for the last visit Summary of demographic characteristics (Total Vaccinated cohort) Step 1 S1AS Group N = 30 S1Alum Group N = 30 Total Group N = 60 Value % Value % Value % Characteristics Parameters or Categories or n or n or n Age (years) at Dose 1 Mean SD Median Minimum Maximum

5 Gender Female Male Geographic Ancestry African Heritage / African American American Indian or Alaskan Native Asian - Central / South Asian Heritage Asian - East Asian Heritage Asian - Japanese Heritage Asian - South East Asian Heritage Native Hawaiian or Other Pacific Islander White - Arabic / North African Heritage White - Caucasian / European Heritage Other Step 2 S2A Group N = 10 S2Alum Group N = 11 Total Group N = 21 Value % Value % Value % Characteristics Parameters or Categories or n or n or n Age (years) at Dose 1 Mean SD Median Minimum Maximum Gender Female Male Geographic Ancestry African Heritage / African American American Indian or Alaskan Native Asian - Central / South Asian Heritage Asian - East Asian Heritage Asian - Japanese Heritage Asian - South East Asian Heritage Native Hawaiian or Other Pacific Islander White - Arabic / North African Heritage White - Caucasian / European Heritage Other Pooling Steps S1AS+S2AS N = 40 S1Alum+ S2Alum Group N = 41 Total N = 81 Value % Value % Value % Characteristics Parameters or Categories or n or n or n Age (years) at Dose 1 Mean SD Median Minimum Maximum Gender Female Male Geographic Ancestry African Heritage / African American American Indian or Alaskan Native Asian - Central / South Asian Heritage Asian - East Asian Heritage Asian - Japanese Heritage Asian - South East Asian Heritage Native Hawaiian or Other Pacific Islander White - Arabic / North African Heritage White - Caucasian / European Heritage Other

6 N = total number of subjects n/% = number / percentage of subjects in a given category Value = value of the considered parameter SD = standard deviation Primary Efficacy Results: Descriptive statistics of cytokines/chemokines concentrations (pg/ml) in plasma, by Multiplex (ATP cohort for innate immunogenicity up to Day 60) Step 1 Parameter Group Dose Time point N Q1 Median Q3 E-selectin S1AS Placebo PRE(D-30) PP(D-30 H1.5) PP(D-30 H3) PP(D-30 H6) PP(D-30 H9) PP(D-30 H12) PP(D-30 H18) PP(D-29) PP(D-28) PP(D-27) PP(D-23) Dose 1 PRE(D0) PI(D0 H1.5) PI(D0 H6) PI(D0 H12) PI(D0 H18) PI(D1) PI(D2) PI(D7) Dose 2 PI(D30) PII(D30 H1.5) PII(D30 H3) PII(D30 H6) PII(D30 H9) PII(D30 H12) PII(D30 H18) PII(D31) PII(D32) PII(D33) PII(D37) S1Alum Placebo PRE(D-30) PP(D-30 H1.5) PP(D-30 H3) PP(D-30 H6) PP(D-30 H9) PP(D-30 H12) PP(D-30 H18) PP(D-29) PP(D-28) PP(D-27) PP(D-23) Dose 1 PRE(D0) PI(D0 H1.5) PI(D0 H6) PI(D0 H12) PI(D0 H18) PI(D1) PI(D2) PI(D7)

7 Dose 2 PI(D30) PII(D30 H1.5) PII(D30 H3) PII(D30 H6) PII(D30 H9) PII(D30 H12) PII(D30 H18) PII(D31) PII(D32) PII(D33) PII(D37) GM-CSF S1AS Placebo PRE(D-30) PP(D-30 H1.5) PP(D-30 H3) PP(D-30 H6) PP(D-30 H9) PP(D-30 H12) PP(D-30 H18) PP(D-29) PP(D-28) PP(D-27) PP(D-23) Dose 1 PRE(D0) PI(D0 H1.5) PI(D0 H6) PI(D0 H12) PI(D0 H18) PI(D1) PI(D2) PI(D7) Dose 2 PI(D30) PII(D30 H1.5) PII(D30 H3) PII(D30 H6) PII(D30 H9) PII(D30 H12) PII(D30 H18) PII(D31) PII(D32) PII(D33) PII(D37) S1Alum Placebo PRE(D-30) PP(D-30 H1.5) PP(D-30 H3) PP(D-30 H6) PP(D-30 H9) PP(D-30 H12) PP(D-30 H18) PP(D-29) PP(D-28) PP(D-27) PP(D-23) Dose 1 PRE(D0) PI(D0 H1.5) PI(D0 H6) PI(D0 H12)

8 PI(D0 H18) PI(D1) PI(D2) PI(D7) Dose 2 PI(D30) PII(D30 H1.5) PII(D30 H3) PII(D30 H6) PII(D30 H9) PII(D30 H12) PII(D30 H18) PII(D31) PII(D32) PII(D33) PII(D37) IFN-γ S1AS Placebo PRE(D-30) PP(D-30 H1.5) PP(D-30 H3) PP(D-30 H6) PP(D-30 H9) PP(D-30 H12) PP(D-30 H18) PP(D-29) PP(D-28) PP(D-27) PP(D-23) Dose 1 PRE(D0) PI(D0 H1.5) PI(D0 H6) PI(D0 H12) PI(D0 H18) PI(D1) PI(D2) PI(D7) Dose 2 PI(D30) PII(D30 H1.5) PII(D30 H3) PII(D30 H6) PII(D30 H9) PII(D30 H12) PII(D30 H18) PII(D31) PII(D32) PII(D33) PII(D37) S1Alum Placebo PRE(D-30) PP(D-30 H1.5) PP(D-30 H3) PP(D-30 H6) PP(D-30 H9) PP(D-30 H12) PP(D-30 H18) PP(D-29) PP(D-28) PP(D-27) PP(D-23)

9 Dose 1 PRE(D0) PI(D0 H1.5) PI(D0 H6) PI(D0 H12) PI(D0 H18) PI(D1) PI(D2) PI(D7) Dose 2 PI(D30) PII(D30 H1.5) PII(D30 H3) PII(D30 H6) PII(D30 H9) PII(D30 H12) PII(D30 H18) PII(D31) PII(D32) PII(D33) PII(D37) IL-10 S1AS Placebo PRE(D-30) PP(D-30 H1.5) PP(D-30 H3) PP(D-30 H6) PP(D-30 H9) PP(D-30 H12) PP(D-30 H18) PP(D-29) PP(D-28) PP(D-27) PP(D-23) Dose 1 PRE(D0) PI(D0 H1.5) PI(D0 H6) PI(D0 H12) PI(D0 H18) PI(D1) PI(D2) PI(D7) Dose 2 PI(D30) PII(D30 H1.5) PII(D30 H3) PII(D30 H6) PII(D30 H9) PII(D30 H12) PII(D30 H18) PII(D31) PII(D32) PII(D33) PII(D37) S1Alum Placebo PRE(D-30) PP(D-30 H1.5) PP(D-30 H3) PP(D-30 H6) PP(D-30 H9) PP(D-30 H12) PP(D-30 H18)

10 PP(D-29) PP(D-28) PP(D-27) PP(D-23) Dose 1 PRE(D0) PI(D0 H1.5) PI(D0 H6) PI(D0 H12) PI(D0 H18) PI(D1) PI(D2) PI(D7) Dose 2 PI(D30) PII(D30 H1.5) PII(D30 H3) PII(D30 H6) PII(D30 H9) PII(D30 H12) PII(D30 H18) PII(D31) PII(D32) PII(D33) PII(D37) IL-18 S1AS Placebo PRE(D-30) PP(D-30 H1.5) PP(D-30 H3) PP(D-30 H6) PP(D-30 H9) PP(D-30 H12) PP(D-30 H18) PP(D-29) PP(D-28) PP(D-27) PP(D-23) Dose 1 PRE(D0) PI(D0 H1.5) PI(D0 H6) PI(D0 H12) PI(D0 H18) PI(D1) PI(D2) PI(D7) Dose 2 PI(D30) PII(D30 H1.5) PII(D30 H3) PII(D30 H6) PII(D30 H9) PII(D30 H12) PII(D30 H18) PII(D31) PII(D32) PII(D33) PII(D37) S1Alum Placebo PRE(D-30) PP(D-30 H1.5) PP(D-30 H3)

11 PP(D-30 H6) PP(D-30 H9) PP(D-30 H12) PP(D-30 H18) PP(D-29) PP(D-28) PP(D-27) PP(D-23) Dose 1 PRE(D0) PI(D0 H1.5) PI(D0 H6) PI(D0 H12) PI(D0 H18) PI(D1) PI(D2) PI(D7) Dose 2 PI(D30) PII(D30 H1.5) PII(D30 H3) PII(D30 H6) PII(D30 H9) PII(D30 H12) PII(D30 H18) PII(D31) PII(D32) PII(D33) PII(D37) IL-2 S1AS Placebo PRE(D-30) PP(D-30 H1.5) PP(D-30 H3) PP(D-30 H6) PP(D-30 H9) PP(D-30 H12) PP(D-30 H18) PP(D-29) PP(D-28) PP(D-27) PP(D-23) Dose 1 PRE(D0) PI(D0 H1.5) PI(D0 H6) PI(D0 H12) PI(D0 H18) PI(D1) PI(D2) PI(D7) Dose 2 PI(D30) PII(D30 H1.5) PII(D30 H3) PII(D30 H6) PII(D30 H9) PII(D30 H12) PII(D30 H18) PII(D31) PII(D32) PII(D33)

12 PII(D37) S1Alum Placebo PRE(D-30) PP(D-30 H1.5) PP(D-30 H3) PP(D-30 H6) PP(D-30 H9) PP(D-30 H12) PP(D-30 H18) PP(D-29) PP(D-28) PP(D-27) PP(D-23) Dose 1 PRE(D0) PI(D0 H1.5) PI(D0 H6) PI(D0 H12) PI(D0 H18) PI(D1) PI(D2) PI(D7) Dose 2 PI(D30) PII(D30 H1.5) PII(D30 H3) PII(D30 H6) PII(D30 H9) PII(D30 H12) PII(D30 H18) PII(D31) PII(D32) PII(D33) PII(D37) IL-3 S1AS Placebo PRE(D-30) PP(D-30 H1.5) PP(D-30 H3) PP(D-30 H6) PP(D-30 H9) PP(D-30 H12) PP(D-30 H18) PP(D-29) PP(D-28) PP(D-27) PP(D-23) Dose 1 PRE(D0) PI(D0 H1.5) PI(D0 H6) PI(D0 H12) PI(D0 H18) PI(D1) PI(D2) PI(D7) Dose 2 PI(D30) PII(D30 H1.5) PII(D30 H3) PII(D30 H6) PII(D30 H9) PII(D30 H12)

13 PII(D30 H18) PII(D31) PII(D32) PII(D33) PII(D37) S1Alum Placebo PRE(D-30) PP(D-30 H1.5) PP(D-30 H3) PP(D-30 H6) PP(D-30 H9) PP(D-30 H12) PP(D-30 H18) PP(D-29) PP(D-28) PP(D-27) PP(D-23) Dose 1 PRE(D0) PI(D0 H1.5) PI(D0 H6) PI(D0 H12) PI(D0 H18) PI(D1) PI(D2) PI(D7) Dose 2 PI(D30) PII(D30 H1.5) PII(D30 H3) PII(D30 H6) PII(D30 H9) PII(D30 H12) PII(D30 H18) PII(D31) PII(D32) PII(D33) PII(D37) IL-4 S1AS Placebo PRE(D-30) PP(D-30 H1.5) PP(D-30 H3) PP(D-30 H6) PP(D-30 H9) PP(D-30 H12) PP(D-30 H18) PP(D-29) PP(D-28) PP(D-27) PP(D-23) Dose 1 PRE(D0) PI(D0 H1.5) PI(D0 H6) PI(D0 H12) PI(D0 H18) PI(D1) PI(D2) PI(D7) Dose 2 PI(D30) PII(D30 H1.5)

14 PII(D30 H3) PII(D30 H6) PII(D30 H9) PII(D30 H12) PII(D30 H18) PII(D31) PII(D32) PII(D33) PII(D37) S1Alum Placebo PRE(D-30) PP(D-30 H1.5) PP(D-30 H3) PP(D-30 H6) PP(D-30 H9) PP(D-30 H12) PP(D-30 H18) PP(D-29) PP(D-28) PP(D-27) PP(D-23) Dose 1 PRE(D0) PI(D0 H1.5) PI(D0 H6) PI(D0 H12) PI(D0 H18) PI(D1) PI(D2) PI(D7) Dose 2 PI(D30) PII(D30 H1.5) PII(D30 H3) PII(D30 H6) PII(D30 H9) PII(D30 H12) PII(D30 H18) PII(D31) PII(D32) PII(D33) PII(D37) IL-5 S1AS Placebo PRE(D-30) PP(D-30 H1.5) PP(D-30 H3) PP(D-30 H6) PP(D-30 H9) PP(D-30 H12) PP(D-30 H18) PP(D-29) PP(D-28) PP(D-27) PP(D-23) Dose 1 PRE(D0) PI(D0 H1.5) PI(D0 H6) PI(D0 H12) PI(D0 H18) PI(D1)

15 PI(D2) PI(D7) Dose 2 PI(D30) PII(D30 H1.5) PII(D30 H3) PII(D30 H6) PII(D30 H9) PII(D30 H12) PII(D30 H18) PII(D31) PII(D32) PII(D33) PII(D37) S1Alum Placebo PRE(D-30) PP(D-30 H1.5) PP(D-30 H3) PP(D-30 H6) PP(D-30 H9) PP(D-30 H12) PP(D-30 H18) PP(D-29) PP(D-28) PP(D-27) PP(D-23) Dose 1 PRE(D0) PI(D0 H1.5) PI(D0 H6) PI(D0 H12) PI(D0 H18) PI(D1) PI(D2) PI(D7) Dose 2 PI(D30) PII(D30 H1.5) PII(D30 H3) PII(D30 H6) PII(D30 H9) PII(D30 H12) PII(D30 H18) PII(D31) PII(D32) PII(D33) PII(D37) IL-6 S1AS Placebo PRE(D-30) PP(D-30 H1.5) PP(D-30 H3) PP(D-30 H6) PP(D-30 H9) PP(D-30 H12) PP(D-30 H18) PP(D-29) PP(D-28) PP(D-27) PP(D-23) Dose 1 PRE(D0) PI(D0 H1.5)

16 PI(D0 H6) PI(D0 H12) PI(D0 H18) PI(D1) PI(D2) PI(D7) Dose 2 PI(D30) PII(D30 H1.5) PII(D30 H3) PII(D30 H6) PII(D30 H9) PII(D30 H12) PII(D30 H18) PII(D31) PII(D32) PII(D33) PII(D37) S1Alum Placebo PRE(D-30) PP(D-30 H1.5) PP(D-30 H3) PP(D-30 H6) PP(D-30 H9) PP(D-30 H12) PP(D-30 H18) PP(D-29) PP(D-28) PP(D-27) PP(D-23) Dose 1 PRE(D0) PI(D0 H1.5) PI(D0 H6) PI(D0 H12) PI(D0 H18) PI(D1) PI(D2) PI(D7) Dose 2 PI(D30) PII(D30 H1.5) PII(D30 H3) PII(D30 H6) PII(D30 H9) PII(D30 H12) PII(D30 H18) PII(D31) PII(D32) PII(D33) PII(D37) IL-6r S1AS Placebo PRE(D-30) PP(D-30 H1.5) PP(D-30 H3) PP(D-30 H6) PP(D-30 H9) PP(D-30 H12) PP(D-30 H18) PP(D-29) PP(D-28)

17 PP(D-27) PP(D-23) Dose 1 PRE(D0) PI(D0 H1.5) PI(D0 H6) PI(D0 H12) PI(D0 H18) PI(D1) PI(D2) PI(D7) Dose 2 PI(D30) PII(D30 H1.5) PII(D30 H3) PII(D30 H6) PII(D30 H9) PII(D30 H12) PII(D30 H18) PII(D31) PII(D32) PII(D33) PII(D37) S1Alum Placebo PRE(D-30) PP(D-30 H1.5) PP(D-30 H3) PP(D-30 H6) PP(D-30 H9) PP(D-30 H12) PP(D-30 H18) PP(D-29) PP(D-28) PP(D-27) PP(D-23) Dose 1 PRE(D0) PI(D0 H1.5) PI(D0 H6) PI(D0 H12) PI(D0 H18) PI(D1) PI(D2) PI(D7) Dose 2 PI(D30) PII(D30 H1.5) PII(D30 H3) PII(D30 H6) PII(D30 H9) PII(D30 H12) PII(D30 H18) PII(D31) PII(D32) PII(D33) PII(D37) IL-7 S1AS Placebo PRE(D-30) PP(D-30 H1.5) PP(D-30 H3) PP(D-30 H6) PP(D-30 H9)

18 PP(D-30 H12) PP(D-30 H18) PP(D-29) PP(D-28) PP(D-27) PP(D-23) Dose 1 PRE(D0) PI(D0 H1.5) PI(D0 H6) PI(D0 H12) PI(D0 H18) PI(D1) PI(D2) PI(D7) Dose 2 PI(D30) PII(D30 H1.5) PII(D30 H3) PII(D30 H6) PII(D30 H9) PII(D30 H12) PII(D30 H18) PII(D31) PII(D32) PII(D33) PII(D37) S1Alum Placebo PRE(D-30) PP(D-30 H1.5) PP(D-30 H3) PP(D-30 H6) PP(D-30 H9) PP(D-30 H12) PP(D-30 H18) PP(D-29) PP(D-28) PP(D-27) PP(D-23) Dose 1 PRE(D0) PI(D0 H1.5) PI(D0 H6) PI(D0 H12) PI(D0 H18) PI(D1) PI(D2) PI(D7) Dose 2 PI(D30) PII(D30 H1.5) PII(D30 H3) PII(D30 H6) PII(D30 H9) PII(D30 H12) PII(D30 H18) PII(D31) PII(D32) PII(D33) PII(D37) IL-8 S1AS Placebo PRE(D-30)

19 PP(D-30 H1.5) PP(D-30 H3) PP(D-30 H6) PP(D-30 H9) PP(D-30 H12) PP(D-30 H18) PP(D-29) PP(D-28) PP(D-27) PP(D-23) Dose 1 PRE(D0) PI(D0 H1.5) PI(D0 H6) PI(D0 H12) PI(D0 H18) PI(D1) PI(D2) PI(D7) Dose 2 PI(D30) PII(D30 H1.5) PII(D30 H3) PII(D30 H6) PII(D30 H9) PII(D30 H12) PII(D30 H18) PII(D31) PII(D32) PII(D33) PII(D37) S1Alum Placebo PRE(D-30) PP(D-30 H1.5) PP(D-30 H3) PP(D-30 H6) PP(D-30 H9) PP(D-30 H12) PP(D-30 H18) PP(D-29) PP(D-28) PP(D-27) PP(D-23) Dose 1 PRE(D0) PI(D0 H1.5) PI(D0 H6) PI(D0 H12) PI(D0 H18) PI(D1) PI(D2) PI(D7) Dose 2 PI(D30) PII(D30 H1.5) PII(D30 H3) PII(D30 H6) PII(D30 H9) PII(D30 H12) PII(D30 H18) PII(D31)

20 PII(D32) PII(D33) PII(D37) IP-10 S1AS Placebo PRE(D-30) PP(D-30 H1.5) PP(D-30 H3) PP(D-30 H6) PP(D-30 H9) PP(D-30 H12) PP(D-30 H18) PP(D-29) PP(D-28) PP(D-27) PP(D-23) Dose 1 PRE(D0) PI(D0 H1.5) PI(D0 H6) PI(D0 H12) PI(D0 H18) PI(D1) PI(D2) PI(D7) Dose 2 PI(D30) PII(D30 H1.5) PII(D30 H3) PII(D30 H6) PII(D30 H9) PII(D30 H12) PII(D30 H18) PII(D31) PII(D32) PII(D33) PII(D37) S1Alum Placebo PRE(D-30) PP(D-30 H1.5) PP(D-30 H3) PP(D-30 H6) PP(D-30 H9) PP(D-30 H12) PP(D-30 H18) PP(D-29) PP(D-28) PP(D-27) PP(D-23) Dose 1 PRE(D0) PI(D0 H1.5) PI(D0 H6) PI(D0 H12) PI(D0 H18) PI(D1) PI(D2) PI(D7) Dose 2 PI(D30) PII(D30 H1.5) PII(D30 H3) PII(D30 H6)

21 PII(D30 H9) PII(D30 H12) PII(D30 H18) PII(D31) PII(D32) PII(D33) PII(D37) MCP-1 S1AS Placebo PRE(D-30) PP(D-30 H1.5) PP(D-30 H3) PP(D-30 H6) PP(D-30 H9) PP(D-30 H12) PP(D-30 H18) PP(D-29) PP(D-28) PP(D-27) PP(D-23) Dose 1 PRE(D0) PI(D0 H1.5) PI(D0 H6) PI(D0 H12) PI(D0 H18) PI(D1) PI(D2) PI(D7) Dose 2 PI(D30) PII(D30 H1.5) PII(D30 H3) PII(D30 H6) PII(D30 H9) PII(D30 H12) PII(D30 H18) PII(D31) PII(D32) PII(D33) PII(D37) S1Alum Placebo PRE(D-30) PP(D-30 H1.5) PP(D-30 H3) PP(D-30 H6) PP(D-30 H9) PP(D-30 H12) PP(D-30 H18) PP(D-29) PP(D-28) PP(D-27) PP(D-23) Dose 1 PRE(D0) PI(D0 H1.5) PI(D0 H6) PI(D0 H12) PI(D0 H18) PI(D1) PI(D2) PI(D7)

22 Dose 2 PI(D30) PII(D30 H1.5) PII(D30 H3) PII(D30 H6) PII(D30 H9) PII(D30 H12) PII(D30 H18) PII(D31) PII(D32) PII(D33) PII(D37) MCP-2 S1AS Placebo PRE(D-30) PP(D-30 H1.5) PP(D-30 H3) PP(D-30 H6) PP(D-30 H9) PP(D-30 H12) PP(D-30 H18) PP(D-29) PP(D-28) PP(D-27) PP(D-23) Dose 1 PRE(D0) PI(D0 H1.5) PI(D0 H6) PI(D0 H12) PI(D0 H18) PI(D1) PI(D2) PI(D7) Dose 2 PI(D30) PII(D30 H1.5) PII(D30 H3) PII(D30 H6) PII(D30 H9) PII(D30 H12) PII(D30 H18) PII(D31) PII(D32) PII(D33) PII(D37) S1Alum Placebo PRE(D-30) PP(D-30 H1.5) PP(D-30 H3) PP(D-30 H6) PP(D-30 H9) PP(D-30 H12) PP(D-30 H18) PP(D-29) PP(D-28) PP(D-27) PP(D-23) Dose 1 PRE(D0) PI(D0 H1.5) PI(D0 H6) PI(D0 H12)

23 PI(D0 H18) PI(D1) PI(D2) PI(D7) Dose 2 PI(D30) PII(D30 H1.5) PII(D30 H3) PII(D30 H6) PII(D30 H9) PII(D30 H12) PII(D30 H18) PII(D31) PII(D32) PII(D33) PII(D37) MCP-4 S1AS Placebo PRE(D-30) PP(D-30 H1.5) PP(D-30 H3) PP(D-30 H6) PP(D-30 H9) PP(D-30 H12) PP(D-30 H18) PP(D-29) PP(D-28) PP(D-27) PP(D-23) Dose 1 PRE(D0) PI(D0 H1.5) PI(D0 H6) PI(D0 H12) PI(D0 H18) PI(D1) PI(D2) PI(D7) Dose 2 PI(D30) PII(D30 H1.5) PII(D30 H3) PII(D30 H6) PII(D30 H9) PII(D30 H12) PII(D30 H18) PII(D31) PII(D32) PII(D33) PII(D37) S1Alum Placebo PRE(D-30) PP(D-30 H1.5) PP(D-30 H3) PP(D-30 H6) PP(D-30 H9) PP(D-30 H12) PP(D-30 H18) PP(D-29) PP(D-28) PP(D-27) PP(D-23)

24 Dose 1 PRE(D0) PI(D0 H1.5) PI(D0 H6) PI(D0 H12) PI(D0 H18) PI(D1) PI(D2) PI(D7) Dose 2 PI(D30) PII(D30 H1.5) PII(D30 H3) PII(D30 H6) PII(D30 H9) PII(D30 H12) PII(D30 H18) PII(D31) PII(D32) PII(D33) PII(D37) MIG S1AS Placebo PRE(D-30) PP(D-30 H1.5) PP(D-30 H3) PP(D-30 H6) PP(D-30 H9) PP(D-30 H12) PP(D-30 H18) PP(D-29) PP(D-28) PP(D-27) PP(D-23) Dose 1 PRE(D0) PI(D0 H1.5) PI(D0 H6) PI(D0 H12) PI(D0 H18) PI(D1) PI(D2) PI(D7) Dose 2 PI(D30) PII(D30 H1.5) PII(D30 H3) PII(D30 H6) PII(D30 H9) PII(D30 H12) PII(D30 H18) PII(D31) PII(D32) PII(D33) PII(D37) S1Alum Placebo PRE(D-30) PP(D-30 H1.5) PP(D-30 H3) PP(D-30 H6) PP(D-30 H9) PP(D-30 H12) PP(D-30 H18)

25 PP(D-29) PP(D-28) PP(D-27) PP(D-23) Dose 1 PRE(D0) PI(D0 H1.5) PI(D0 H6) PI(D0 H12) PI(D0 H18) PI(D1) PI(D2) PI(D7) Dose 2 PI(D30) PII(D30 H1.5) PII(D30 H3) PII(D30 H6) PII(D30 H9) PII(D30 H12) PII(D30 H18) PII(D31) PII(D32) PII(D33) PII(D37) MIP-1 alpha S1AS Placebo PRE(D-30) PP(D-30 H1.5) PP(D-30 H3) PP(D-30 H6) PP(D-30 H9) PP(D-30 H12) PP(D-30 H18) PP(D-29) PP(D-28) PP(D-27) PP(D-23) Dose 1 PRE(D0) PI(D0 H1.5) PI(D0 H6) PI(D0 H12) PI(D0 H18) PI(D1) PI(D2) PI(D7) Dose 2 PI(D30) PII(D30 H1.5) PII(D30 H3) PII(D30 H6) PII(D30 H9) PII(D30 H12) PII(D30 H18) PII(D31) PII(D32) PII(D33) PII(D37) S1Alum Placebo PRE(D-30) PP(D-30 H1.5) PP(D-30 H3)

26 PP(D-30 H6) PP(D-30 H9) PP(D-30 H12) PP(D-30 H18) PP(D-29) PP(D-28) PP(D-27) PP(D-23) Dose 1 PRE(D0) PI(D0 H1.5) PI(D0 H6) PI(D0 H12) PI(D0 H18) PI(D1) PI(D2) PI(D7) Dose 2 PI(D30) PII(D30 H1.5) PII(D30 H3) PII(D30 H6) PII(D30 H9) PII(D30 H12) PII(D30 H18) PII(D31) PII(D32) PII(D33) PII(D37) MIP-1 beta S1AS Placebo PRE(D-30) PP(D-30 H1.5) PP(D-30 H3) PP(D-30 H6) PP(D-30 H9) PP(D-30 H12) PP(D-30 H18) PP(D-29) PP(D-28) PP(D-27) PP(D-23) Dose 1 PRE(D0) PI(D0 H1.5) PI(D0 H6) PI(D0 H12) PI(D0 H18) PI(D1) PI(D2) PI(D7) Dose 2 PI(D30) PII(D30 H1.5) PII(D30 H3) PII(D30 H6) PII(D30 H9) PII(D30 H12) PII(D30 H18) PII(D31) PII(D32) PII(D33)