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

Sanjay Lalwani, Sukanta Chatterjee, Sundaram Balasubramanian, Ashish Bavdekar, Shailesh Mehta, Sanjoy Datta, Michael Povey, Ouzama Henry, Sanjay Lalwani, Sukanta Chatterjee, Sundaram Balasubramanian, Ashish Bavdekar, Shailesh Mehta, Sanjoy Datta, Michael Povey, Ouzama Henry

Abstract

Objective: This 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.

Design: Phase III, open, randomised, non-inferiority study.

Setting: 6 tertiary care hospitals located in India.

Participants: Healthy participants aged 9-10 months not previously vaccinated against/exposed to measles, mumps, rubella and varicella or without a history of these diseases.

Interventions: Participants 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 measures: To 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.

Results: Seroconversion 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.

Conclusions: The 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 number: NCT00969436.

Keywords: India; immunogenicity; measles-mumps-rubella-varicella vaccine; safety; vaccination schedule.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Figures

Figure 1
Figure 1
Participant disposition (ATP, according-to-protocol; MMR, measles-mumps-rubella vaccine; MMRV, measles-mumps-rubella-varicella vaccine; MMR+V, MMR+varicella vaccine).
Figure 2
Figure 2
(A) Prevalence of fever during the 43-day postvaccination period after dose 1 (total vaccinated cohort). (B) Prevalence of fever during the 43-day postvaccination period after dose 2 (total vaccinated cohort). MMR, measles-mumps-rubella vaccine; MMRV, measles-mumps-rubella-varicella vaccine; MMR+V, MMR+varicella vaccine.

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Source: PubMed

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