Study to Assess the Immunogenicity and Safety of GSK's Investigational Vaccine (GSK3277511A) When Given to Healthy Smokers and Ex-smokers After Administration of Shingrix Vaccine

Antibody concentrations as measured by ELISA (Enzyme-linked immunosorbent assay) and expressed as adjusted (ANCOVA model) GMCs in ELISA units per milliliter (EU/mL). Cut-off value for the assay is 153, 16, 8 and 28 EU/mL for Anti-PD, Anti-PE, Anti-PilA and Anti-UspA2 antibodies respectively. The ANCOVA model includes study group, smoking status (current or former), age category (50-59, 60-69, 70-80 years of age) and center as factors and the antibody concentration before Dose 1 as covariate. As per protocol set (PPS) sample size was not met in Sh\_NTHi\_Mcat\_3 and Sh\_NTHi-Mcat\_6 groups then timeframe was adapted as follows: At 1 month after dose 2 of NTHi-Mcat vaccine (Day 181 in Sh\_NTHi-Mcat\_1 group and Day 91 in NTHi-Mcat group)

Time frame: At 1 month after dose 2 of NTHi-Mcat vaccine (Day 181, in Sh_NTHi-Mcat_1 group and Day 91 in NTHi-Mcat group)

Population: Analysis was performed on the per protocol set (PPS) which included all subjects who received full study treatment course to which they were randomized and had post-vaccination immunogenicity data minus subjects with protocol deviations that lead to exclusion.According to protocol,as PPS sample size for Sh\_NTHI\_Mcat\_3 and Sh\_NTHI\_Mcat\_6 Groups was not met,those were not part of the analysis. Shingrix-Only Group was not included in this analysis,as subjects didn't receive the NTHi MCAT vaccine.

GMCs and their 95% CI for each of the antibodies, as measured by ELISA, were calculated (the GMCs were computed by taking the Anti-log of the mean of the log concentration transformations)

Time frame: Before the first dose of NTHi-Mcat vaccine (Day 91, Day 151 and Day 241 for Sh_NTHi-Mcat_1, Sh_NTHi-Mcat_3 and Sh_NTHi-Mcat_6 group, respectively, and Day 1 for NTHi-Mcat group)

Population: Analysis was performed on the PPS which included all subjects who received full study treatment course to which they were randomized and had post-vaccination immunogenicity data minus subjects with protocol deviations that lead to exclusion. Subjects from the Shingrix-Only Group were not included in this analysis, as they didn't receive the NTHi MCAT vaccine.

GMCs and their 95% CI for each of the antibodies, as measured by ELISA, were calculated (the GMCs were computed by taking the Anti-log of the mean of the log concentration transformations) before the first dose of NTHi-Mcat vaccine

Time frame: At one month after the second dose of NTHi-Mcat vaccine (Day 181, 241, 331 in the Sh_NTHi-Mcat_1, Sh_NTHi-Mcat_3 and Sh_NTHi-Mcat_6 group, respectively, and Day 91 in the NTHi-Mcat group)

Population: Analysis was performed on the PPS which included all subjects who received full study treatment course to which they were randomized and had post-vaccination immunogenicity data minus subjects with protocol deviations that lead to exclusion. Subjects from the Shingrix-Only Group were not included in this analysis, as they didn't receive the NTHi MCAT vaccine.

Frequency of specific CD4+ T-cells was measured by flow cytometry ICS expressing at least 2 different markers among CD40L, IL-2, IL-13, IL-17, TNF-α and IFN-γ, upon in vitro stimulation

Time frame: At one month after second dose of NTHi-Mcat vaccine (Day 181, Day 241 and Day 331 in the Sh_NTHi-Mcat_1, Sh_NTHi-Mcat_3 and Sh_NTHi-Mcat_6 group, respectively, and Day 91 in the NTHi-Mcat group)

Population: Analysis was performed on CMI sub-cohort, which included approximately 60 subjects (15/each group), for which an additional blood sample was taken at each pre-defined time point (sub-cohort selected from sites able to process the blood samples according to GSK procedures for peripheral blood mononuclear cell preparation). Subjects from the Shingrix-Only Group were not included in this analysis, as they didn't receive the NTHi MCAT vaccine.

Frequency of specific CD4+ T-cells was measured by flow cytometry intracellular cytokine staining (ICS) expressing at least 2 different markers among CD40 Ligand (CD40L), interleukin (IL)-2, IL-13, IL-17, tumour necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ), upon in vitro stimulation

Time frame: Before the first dose of NTHi-Mcat vaccine (Day 91, Day 151 and Day 241 in the Sh_NTHi-Mcat_1, Sh_NTHi-Mcat_3 and Sh_NTHi-Mcat_6 group, respectively, and Day 1 in the NTHi-Mcat group)

Population: Analysis was performed on Cell-Mediated immune (CMI) sub-cohort, which included approximately 60 subjects (15/each group), for which an additional blood sample was taken at each pre-defined timepoint (sub-cohort selected from sites able to process the blood samples according to GSK procedures for peripheral blood mononuclear cell preparation). Subjects from the Shingrix-Only Group were not included in this analysis, as they didn't receive the NTHi MCAT vaccine.

A seropositive subject is defined as a subject whose Anti-PD, Anti-PE, Anti-PilA and Anti-UspA2 antibody concentrations are greater than or equal to the assay cut-off value. Seropositivity rates with 95% CI is defined using the assay lower limit of quantification (LLOQ). Cut-off value for the assay is 153, 16, 8 and 28 EU/mL for Anti-PD, Anti-PE, Anti-PilA and Anti-UspA2 antibodies respectively

Time frame: Before the first dose of NTHi-Mcat vaccine (Day 91, Day 151 and Day 241 in the Sh_NTHi-Mcat_1, Sh_NTHi-Mcat_3 and Sh_NTHi-Mcat_6 group, respectively, and Day 1 in the NTHi-Mcat group)

Population: Analysis was performed on the PPS which included all subjects who received full study treatment course to which they were randomized and had post-vaccination immunogenicity data minus subjects with protocol deviations that lead to exclusion. Subjects from the Shingrix-Only Group were not included in this analysis, as they didn't receive the NTHi MCAT vaccine.

A seropositive subject is defined as a subject whose Anti-PD, Anti-PE, Anti-PilA and Anti-UspA2 antibody concentrations are greater than or equal to the assay cut-off value. Seropositivity rates with 95% CI are defined using the assay (LLOQ). Cut-off value for the assay is 153, 16, 8 and 28 EU/mL for Anti-PD, Anti-PE, Anti-PilA and Anti-UspA2 antibodies respectively

Time frame: At one month after the second dose of NTHi-Mcat vaccine (Day 181, 241, 331 in the Sh_NTHi-Mcat_1, Sh_NTHi-Mcat_3 and Sh_NTHi-Mcat_6 group, respectively, and Day 91 in the NTHi-Mcat group)

Population: Analysis was performed on the PPS which included all subjects who received full study treatment course to which they were randomized and had post-vaccination immunogenicity data minus subjects with protocol deviations that lead to exclusion. Subjects from the Shingrix-Only Group were not included in this analysis, as they didn't receive the NTHi MCAT vaccine.

pIMD's are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune aetiology

Time frame: From Day 332 up to and including Day 661 (Epoch 002)

Population: Analysis was performed on the ES which included all subjects who received at least 1 dose of the study treatment.

pIMD's are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune aetiology.

Time frame: From Day 1 up to and including Day 331 (Epoch 001)

Population: Analysis was performed on the ES which included all subjects who received at least 1 dose of the study treatment.

The percentage of subjects with at least one SAE, regardless of intensity or relationship to vaccination, from Day 332 up to and including Day 661, are reported for each group. An SAE is defined as any untoward medical occurrence that resulted in death, was life-threatening, requires hospitalization or prolongation of hospitalization, resulted in disability/incapacity in a subject or was a congenital anomaly/birth defect in the offspring of a study subject. AE(s) considered as SAE(s) also include invasive or malignant cancers, intensive treatment in an emergency room or at home for allergic bronchospasm, blood dyscrasias or convulsions that do not result in hospitalization, as per the medical or scientific judgement of the physician.

Time frame: From Day 332 up to and including Day 661 (Epoch 002)

Population: Analysis was performed on the ES which included all subjects who received at least 1 dose of the study treatment.

The percentage of subjects with at least one SAE, regardless of intensity or relationship to vaccination, from Day 1 up to and including Day 331, were reported for each group An SAE is defined as any untoward medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity in a subject or was a congenital anomaly/birth defect in the offspring of a study subject. AE(s) considered as SAE(s) also include invasive or malignant cancers, intensive treatment in an emergency room or at home for allergic bronchospasm, blood dyscrasias or convulsions that do not result in hospitalization, as per the medical or scientific judgement of the physician

Time frame: From Day 1 up to and including Day 331 (Epoch 001)

Population: Analysis was performed on the Exposed Set (ES) which included all subjects who received at least 1 dose of the study treatment.

An unsolicited adverse event is an adverse event that was not solicited using a Subject Diary and that was spontaneously communicated by a subject who has signed the informed consent. The percentage of subjects with at least one unsolicited AE, regardless of intensity or relationship to vaccination, during the 30-day follow-up period after any NTHi-Mcat vaccine dose are reported for each group. Any solicited symptom with onset outside the specified period of follow-up for solicited symptoms is reported as an unsolicited adverse event

Time frame: During the 30-day follow-up period (i.e. day of vaccination and 29 subsequent days) after Dose 1 and after Dose 2 of NTHi-Mcat vaccine

Population: Analysis was performed on the Unsolicited safety set which included all subjects who receive at least 1 dose of the study treatment and who have unsolicited safety data

The percentage of subjects with at least one general solicited AE, regardless of intensity, during the 7-day follow-up period after each NTHi-Mcat vaccine dose, are reported by study group. Assessed solicited general symptoms were Fatigue, Gastrointestinal symptoms (nausea, vomiting, diarrhoea and/or abdominal pain), Headache, Myalgia, Chills and Fever (oral cavity or axillary route - temperature equal or higher than \[\>=\] 37.5 degrees Celsius \[°C\])

Time frame: During the 7-day follow-up period (i.e. day of vaccination and 6 subsequent days) after Dose 1 and after Dose 2 of NTHi-Mcat vaccine

Population: Analysis was performed on the SSS which included all subjects who received at least 1 dose of the study treatment and who have solicited safety data

The percentage of subjects with at least one local solicited AE, regardless of intensity, during the 7-day follow-up period after each NTHi-Mcat vaccine dose, are reported by study group. Assessed local symptoms were pain, redness and swelling. Any local injection site redness/swelling is scored as follows: diameter \>=20 milli-meters

Time frame: During the 7-day follow-up period (i.e. day of vaccination and 6 subsequent days) after Dose 1 and after Dose 2 of NTHi-Mcat vaccine

Population: Analysis was performed on the Solicited safety set (SSS) which included all subjects who received at least 1 dose of the study treatment and who have solicited safety data