Solicited local symptoms assessed were pain, redness and swelling. Any was defined as any solicited local symptom reported irrespective of intensity. Grade 3 pain was defined as significant pain at rest that prevented normal everyday activities. Grade 3 redness and swelling was greater than 100 millimeters (mm) i.e. >100mm.

Analysis was performed on the Total Vaccinated cohort, which included all vaccinated subjects for whom safety data were available.

Solicited general symptoms assessed were fatigue, gastrointestinal symptoms, headache, joint pain, muscle ache, shivering, sweating and fever [oral temperature above 38.0 degrees Celsius (°C)]. Gastrointestinal symptoms included nausea, vomiting, diarrhea and/or abdominal pain. Any = any solicited general symptom reported irrespective of intensity and relationship to vaccination. Related = symptoms considered by the investigator to have a causal relationship to vaccination. Grade 3 symptoms = symptoms that prevented normal activity. Grade 3 fever = axillary temperature ≥ 39.0°C and ≤40°C.

Analysis was performed on the Total Vaccinated cohort, which included all vaccinated subjects for whom safety data were available.

Unsolicited AE covers any AE reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as occurrence of any unsolicited symptom regardless of intensity grade or relation to vaccination. Related was defined as an unsolicited symptom assessed as causally related to the study vaccination.

Analysis was performed on the Total Vaccinated cohort, which included all vaccinated subjects for whom safety data were available.

MAEs refer to events that required medical attention defined as hospitalization, an emergency room visit or a visit to or from medical personnel (medical doctor) for any reason. Related = symptom assessed by the investigator as causally related to the study vaccination.

Analysis was performed on the Total Vaccinated cohort included all vaccinated subjects for whom safety data were available.

Potential immune-mediated diseases (pIMDs) were defined as a subset of adverse events (AEs) that included autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune aetiology. Any was defined as occurrence of any pIMD regardless of intensity grade or relation to vaccination. Related was defined as pIMD(s) considered by the investigator to have a causal relationship to vaccination.

Analysis was performed on the Total Vaccinated cohort, which included all vaccinated subjects for whom safety data were available.

A serious adverse event was any untoward medical occurrence that: resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity or was a congenital anomaly/birth defect in the offspring of a study subject. Any was defined as occurrence of any symptom regardless of intensity grade or relation to vaccination and related was an event assessed by the investigator as causally related to the study vaccination.

Analysis was performed on the Total Vaccinated cohort, which included all vaccinated subjects for whom safety data were available.

Any = Occurrence of any adverse pregnancy outcomes regardless of intensity grade or relation to study vaccination. Related = Adverse pregnancy outcomes assessed by the investigator as causally related to the study vaccination

Analysis was performed on the Total Vaccinated cohort which included all vaccinated subjects for whom safety data were available.

The assessed parameters for change from baseline were Physical functioning (PF), Physical-health related role limitations (RP), Bodily pain (BP), General health (GH), Vitality (VT), Social functioning (SF), Emotional health related role limitations (RE), Mental health (MH) defined as subscale component, and physical (PCS) and mental (MCS) component defined as summary components, and Quality Adjusted Life Years (QALY). See methodology details in outcome 11 description. For all subscale components, scores range from 0 to 100, with high scores indicating high levels of functioning/quality of life. Subscale component scores are averaged to compute the summary component score and QALY score. Median and range of the change from baseline of the SF-36v2 score are presented for each component and time point. Analyses by age category were not performed for the daily SF-36v2 questionnaire results.

Analysis was performed on the Total Vaccinated cohort which included all vaccinated subjects. Only the subjects with available score test results were included.

The assessed parameters for change from baseline were Physical functioning (PF), Physical-health related role limitations (RP), Bodily pain (BP), General health (GH), Vitality (VT), Social functioning (SF), Emotional health related role limitations (RE), Mental health (MH) defined as subscale component. For all subscale components, scores range from 0 to 100, with high scores indicating high levels of functioning/quality of life. Median and range of the change from baseline of the SF-36 score are presented for each component and time point. Analysis was carried out for all subjects regardless of age stratum.

Analysis was performed on the Total Vaccinated cohort which included all vaccinated subjects. Only the subjects with available score test results were included.

The assessed parameters for change from baseline were physical and mental component defined as summary components (PCS and MCS) or general health scores (GHS). For all subscale component, scores range from 0 to 100, with high scores indicating high levels of functioning/quality of life. Subscale component scores are averaged to compute the summary component score. Median and range of the change from baseline of the SF-36v2 score are presented for each summary component and time point. Analysis was carried out for all subjects regardless of age stratum.

Analysis was performed on the Total Vaccinated cohort which included all vaccinated subjects. Only the subjects with available score test results were included.

The assessed parameters for change from baseline were QALY scores. The methodology used for the analysis of the SF-36v2 questionnaire was detailed in Ware et al [Ware 2008]. The QualityMetric Health Outcomes Scoring Software was used to generate a Quality of Life analysis dataset based on the SF-36 questionnaire. QoL data were transformed to generate Quality-Adjusted Life Years (QALY) scores. A standard algorithm was developed for processing subjects' answers and producing QALY scores. For all subscale components, scores range from 0 to 100, with high scores indicating high levels of functioning/quality of life. Median and range of the change from baseline of the SF-36v2 score are presented for each time point. Analysis was carried out for all subjects regardless of age stratum.

Analysis was performed on the Total Vaccinated cohort which included all vaccinated subjects. Only the subjects with available score test results were included.

The assessed parameters for change from baseline were Physical functioning (PF), Physical-health related role limitations (RP), Bodily pain (BP), General health (GH), Vitality (VT), Social functioning (SF), Emotional health related role limitations (RE), Mental health (MH) defined as subscale component, and physical (PCS) and mental (MCS) component defined as summary components, and Quality Adjusted Life Years (QALY). For all subscale component, scores range from 0 to 100, with high scores indicating high levels of functioning/quality of life. Subscale component scores are averaged to compute the summary component score and QALY score. Median and range of the change from baseline of the SF-36v2 score are presented for each component and time point. Analyses by age category were not performed for the daily SF-36v2 questionnaire results.

Analysis was performed on the Total Vaccinated cohort which included all vaccinated subjects who reported at least one local or general solicited AE post first vaccination. Only the subjects with available score test results were included.

Median and range of the change from baseline of the SF-36v2 score are presented for each component and time point. The assessed parameters for change from baseline were Physical functioning (PF), Physical-health related role limitations (RP), Bodily pain (BP), General health (GH), Vitality (VT), Social functioning (SF), Emotional health related role limitations (RE), Mental health (MH) defined as subscale component. For all subscale component, scores range from 0 to 100, with high scores indicating high levels of functioning/quality of life. There was only 1 study participant > 64 years of age and that experienced no grade 3 solicited symptoms. Hence, weekly questionnaire was assessed only on the 18-64 age category subjects.

Analysis was performed on the Total Vaccinated cohort (18-64 years of age) which included all vaccinated subjects within 18 to 64 years of age and for whom safety data were available. Only subjects with available score test results were included.

Median and range of the change from baseline of the SF-36v2 score are presented for each component and time point. The assessed parameters for change from baseline were physical and mental component defined as summary components (PCS and MCS) or general health scores (GHS). For all subscale component, scores range from 0 to 100, with high scores indicating high levels of functioning/quality of life. Subscale component scores are averaged to compute the summary component score. There was only 1 study participant > 64 years of age and that experienced no grade 3 solicited symptoms. Hence, weekly questionnaire was assessed only on the 18-64 age category subjects.

Analysis was performed on the Total Vaccinated cohort (18-64 years of age) which included all vaccinated subjects within 18 to 64 years of age and for whom safety data were available. Only the subjects with available score test results were included.

Median and range of the change from baseline of the SF-36v2 score are presented for each time point. The assessed parameters for change from baseline were QALY scores. For all subscale component, scores range from 0 to 100, with high scores indicating high levels of functioning/quality of life. There was only 1 study participant > 64 years of age and that experienced no grade 3 solicited symptoms. Hence, weekly questionnaire was assessed only on the 18-64 age category subjects.

Analysis were performed on the Total Vaccinated cohort (18-64 years of age) which included all vaccinated subjects within 18 to 64 years of age and for whom safety data were available. Only subjects with score test results were included.

The assessed parameters were Physical functioning (PF), Physical-health related role limitations (RP), Bodily pain (BP), General health (GH), Vitality (VT), Social functioning (SF), Emotional health related role limitations (RE), Mental health (MH) and physical and mental component summary measures (PCS, MCS) and QALY for subjects who reported unsolicited AEs in the first 7 days after Dose 1. Only negative deviations from baseline were considered. On any variable, if there was a negative deviation from baseline, then if and only if the value returned to baseline or above within the 7 days after dose 1, the number of days required to return to baseline or above was calculated. On any variable, if there was no variation within the 7 days after dose 1, then nothing was counted. If there was more than one negative deviation from baseline and more than one recovery, then only the first was considered. Analyses by age category were not performed for the daily SF-36v2 questionnaire results.

Analysis was performed on the Total Vaccinated cohort which included all vaccinated subjects who reported an unsolicited AE in the 7 days after Dose 1. Only subjects with negative deviations from baseline were analyzed.

The analysis of Quantitative differences between SF-36v2 questionnaire responses, and the solicited local and general adverse event data provided on diary cards was invalidated as the differences in scale between the measures could not be reconciled.

The analysis of Quantitative differences between SF-36v2 questionnaire responses, and the solicited local and general adverse event data provided on diary cards was invalidated as the differences in scale between the measures could not be reconciled.