Effects of low dose everolimus and/or BEZ235 on vaccine response in the elderly

INTERVENTION: Everolimus, BEZ235 and corresponding placebo tablets and capsules will be dosed on a once‐daily basis. Subjects will receive placebo, 0.1 mg or 0.5 mg everolimus daily, 10 mg BEZ235 daily, or a combination of 0.1 mg everolimus and 10 mg BEZ235 daily for 6 weeks. Subjects will use a patient diary to record how many tablets are taken on each day. Subjects are required to bring back tablets or empty boxes to the clinic for drug accountability. Standard flu vaccine (FluVax) will be given at day 56. Fluvax dose is 0.5ml and mode of delivery is intramuscular or deep subcutaneous injection. CONDITION: Immune response to vaccination PRIMARY OUTCOME: To assess the efficacy of low dose everolimus and/or BEZ235 in enhancing the immune response to vaccination in the elderly as determined by the change in hemagglutination inhibition (HI) geometric mean titers (GMTs) 4‐weeks post influenza vaccination. ; ; Assessed using serum assays. To assess the safety and tolerability of low dose everolimus and/or BEZ235 in the elderly. Assessed via adverse event reporting and safety labs (chemistry and haematology lab tests). ; ; Known adverse events for both BEZ and everolimus include stomatitis, nausea, vomiting and diarrhoea. SECONDARY OUTCOME: To assess the PK of low dose everolimus and/or BEZ235 in the elderly. ; ; Assessed using plasma assays and whole blood assays. To assess the efficacy of low dose everolimus and/or BEZ235 in enhancing the immune response to vaccination in the elderly as determined by rates of seroconversion and seroprotection 4‐weeks post influenza vaccination ; ; Assessed using serum assays. To assess the efficacy of low dose everolimus and/or BEZ235 in enhancing the immune response to vaccination in the elderly as determined by the change in HI GMTs 1‐week post influenza vaccination. ; ; Assessed using serum assays. INCLUSION CRITERIA: Informed Consent obtained >= 65 yo, male and female >=40kg