In sub-cohort 1, drowsiness and loss of appetite were also recorded from D0 to D3, and varicella-like rash was recorded from D0 to D42, as solicited general AEs (Number 4). Unsolicited AEs were recorded from D0 to D42, whereas SAEs were documented throughout the entire study period (D0C180). booster reactions, we used antibody concentration thresholds that were approved by the Food and Drug Administration (FDA) as endpoints defining active immunization offering clinical benefit. The anti-VZV threshold was approved from the FDA as threshold generally used in earlier studies.29 Seroresponse was defined as an IgG antibody concentration 200 mIU/mL for anti-measles, 10 EU/mL for anti-mumps, 10 IU/mL for anti-rubella, and 75 mIU/mL for anti-VZV, at D42, and did not take into account pre-vaccination concentrations (since most of the participants were expected to be seroresponsive before their second dose of MMR vaccine and VV vaccine, administered with this study). Booster reactions for PT, FHA, and PRN antigens were defined as: For participants with pre-vaccination antibody concentration below the assay cut-off (i.e., 2.693 IU/mL for anti-PT, 2.046 IU/mL for anti-FHA, and 2.187 IU/mL for anti-PRN): post-vaccination antibody concentration 4 instances the assay cut-off. For participants with pre-vaccination antibody concentration between the assay cut-off and 4 instances above the assay cut-off: post-vaccination antibody concentration 4 instances the pre-vaccination antibody concentration. For participants with pre-vaccination antibody concentration 4 instances the assay cut-off: post-vaccination antibody concentration 2 times the pre-vaccination antibody concentration. Booster reactions for DT and TT antigens were defined as: For participants with pre-vaccination concentration 0.1 IU/mL (i.e., below the seroprotection threshold): post-vaccination antibody concentrations 0.4 IU/mL. For participants with pre-vaccination concentration 0.1 IU/mL: an increase in antibody concentrations 4 instances the pre-vaccination concentration 43?days after vaccination. Demethylzeylasteral Reactogenicity and security assessments In all the sub-cohorts, solicited local AEs (injection site pain, redness, and swelling) were recorded from D0 to D3. MMR-specific solicited general AEs were recorded from AMLCR1 D0 to D42 (Number 4) and included: fever (defined as temp 38.0C), rash (including measles/rubella-like and any rash), swelling of the parotid or additional salivary glands, symptoms suggestive of meningeal irritation including febrile convulsions and headaches. In sub-cohort 1, drowsiness and loss of hunger were also recorded from D0 to D3, and varicella-like rash was recorded from D0 to D42, as solicited general AEs (Number 4). Unsolicited AEs were recorded from D0 to D42, whereas SAEs were documented throughout the entire study period (D0C180). NOCDs (e.g., autoimmune disorders, asthma, type I diabetes, vasculitis, celiac disease, conditions associated with sub-acute or chronic thrombocytopenia, and allergies) were recorded from D0 to D180. We graded solicited AEs relating to their intensity (grade 1C3). Grade 3 was defined as: limb spontaneously painful or child cried when limb was relocated (pain); redness or swelling of diameter 50 mm; temp 39.5C (fever); AE avoiding normal, everyday activities (any rash, febrile convulsion, drowsiness, unsolicited AEs); swelling with accompanying general symptoms (parotid/salivary gland swelling); not eating whatsoever (loss of hunger). All solicited local (injection site) reactions were considered causally related to vaccination. Causality of all additional AEs was assessed from the investigator. Statistical analyses We planned to enroll 4000 children with this study: 1096 in sub-cohort 1 (MMR-RIT, N =?822; MMR II, N =?274), 1096 in sub-cohort 2 (MMR-RIT, N =?822; Demethylzeylasteral MMR II, N =?274), and 1808 in sub-cohort Demethylzeylasteral 3 (MMR-RIT, N =?1356; MMR II, N =?452). Presuming a 20% non-evaluable rate in the according-to-protocol cohort for immunogenicity, 876 children (MMR-RIT, N =?657; MMR II, N =?219) would be evaluable in each of the sub-cohorts 1 and 2. All the immunogenicity objectives (main and secondary) were statistically run. The 4 co-primary objectives were assessed in parallel. To control the.