Immunogenicity and safety of early vaccination with two doses of a combined measles-mumps-rubella-varicella vaccine in healthy Indian children from 9 months of age: a phase III, randomised, non-inferiority trial

• Published in: BMJ open 2015-09, Vol.5 (9), p.e007202-e007202
• Main Authors: Lalwani, Sanjay, Chatterjee, Sukanta, Balasubramanian, Sundaram, Bavdekar, Ashish, Mehta, Shailesh, Datta, Sanjoy, Povey, Michael, Henry, Ouzama
• Format: Article
• Language: English
• Subjects: Age; Chicken pox; Chickenpox Vaccine - administration & dosage; Disease; Epidemics; Female; Fever; Health care; Healthy Volunteers; Humans; Immunization; Immunization Schedule; India - epidemiology; Infant; Male; Measles; Measles-Mumps-Rubella Vaccine - administration & dosage; Mortality; Mumps; Paediatrics; Patient Safety; Rubella; Tertiary Care Centers; Treatment Outcome; Vaccination - methods; Vaccines; Vaccines, Combined - administration & dosage
• ISSN: 2044-6055; 2044-6055
• DOI: 10.1136/bmjopen-2014-007202

ObjectiveThis study (NCT00969436) compared the immunogenicity and safety of measles-mumps-rubella (MMR) followed by MMR+varicella (V) vaccines to (1) 2 doses of combined MMRV and (2) MMR followed by MMRV, in Indian children.DesignPhase III, open, randomised, non-inferiority study.Setting6 tertiary care hospitals located in India.ParticipantsHealthy participants aged 9–10 months not previously vaccinated against/exposed to measles, mumps, rubella and varicella or without a history of these diseases.InterventionsParticipants were randomised (2:2:1) to receive 2 doses of either MMRV (MMRV/MMRV group) or MMR followed by MMRV (MMR/MMRV group) or MMR followed by MMR+V (MMR/MMR+V, control group) at 9 and 15 months of age. Antibody titres against measles, mumps and rubella were measured using ELISA and against varicella using an immunofluorescence assay.Main outcome measuresTo demonstrate non-inferiority of the 2 vaccination regimens versus the control in terms of seroconversion rates, defined as a group difference with a lower bound of the 95% CI >−10% for each antigen, 43 days postdose 2. Parents/guardians recorded solicited local and general symptoms for a 4-day and 43-day period after each vaccine dose, respectively.ResultsSeroconversion rates postdose 1 ranged from 87.5% to 93.2% for measles, 83.3% to 86.1% for mumps and 98.7% to 100% for rubella across the 3 vaccine groups. The seroconversion rates postdose 2 were 100% for measles, mumps and rubella and at least 95.8% for varicella across the 3 vaccine groups. Non-inferiority of MMRV/MMRV and MMR/MMRV to MMR/MMR+V was achieved for all antigens, 43 days postdose 2. The 3 vaccination regimens were generally well tolerated in terms of solicited local and general symptoms.ConclusionsThe immune responses elicited by the MMRV/MMRV and MMR/MMRV vaccination regimens were non-inferior to those elicited by the MMR/MMR+V regimen for all antigens. The 3 vaccination schedules also exhibited an acceptable safety profile in Indian children.Trial registration numberNCT00969436.