Immune non-interference and safety study of Vi-DT typhoid conjugate vaccine with a measles, mumps and rubella containing vaccine in 9-15 months old Nepalese infants.

ABSTRACT

BACKGROUND: Typhoid fever is a common disease in developing countries especially in the Indian subcontinent and Africa. The available typhoid conjugate vaccines (TCV) have been found to be highly immunogenic in infants and children less than 2 years of age. Many countries are planning to adopt TCV in their routine EPI programs around 9 months of age when measles containing vaccines are given. Therefore, Vi-DT TCV was tested in 9-15 months aged healthy infants in Nepal to demonstrate non-interference with a measles containing vaccine. METHODS: This was a randomized, open label, phase III study to assess the immune non-interference, safety, and reactogenicity of Vi-DT typhoid conjugate vaccine when given concomitantly with measles, mumps and rubella (MMR) vaccine. A total of 360 participants aged 9-15 months were enrolled and randomized equally into Vi-DT + MMR (180 participants) or MMR alone (180 participants) group and were evaluated for immunogenicity and safety 28 days post vaccination. RESULTS: Using the immunogenicity set, difference between proportions (95% CI) of the Vi-DT + MMR group vs MMR alone group were -2.73% (-8.85, 3.38), -3.19% (-11.25, 4.88) and 2.91% (-3.36, 9.18) for sero-positivity rate of anti-measles, anti-mumps and anti- rubella, respectively. Only the lower bound of the range in difference of the proportions for sero-positivity rate of anti-mumps did not satisfy the non-inferiority criteria as it was above the -10% limit, which may not be of clinical significance. These results were confirmed in the per protocol set. There were no safety concerns reported from the study and both Vi-DT + MMR and MMR alone groups were comparable in terms of solicited and unsolicited adverse events . CONCLUSIONS: Results indicated that there is non-interference of MMR vaccine with Vi-DT and Vi-DT conjugate vaccine could be considered as an addition to the EPI schedule among children at risk of contracting typhoid.