P Sabitha, M R Prabha Adhikari, Abhijit Chowdary, Malathi Prabhu, Mohammad Soofi, Meenakshi Shetty, Asha Kamath, S S Lokranjan, S S Bangera
Background: The recent emergence of multi-drug resistant Salmonella strains highlights the need for better prevantive measure, including vaccination. Safe and immunologic vaccines have been developed based on purified Vi polysaccharide.
Objective: To compare the immune response elicited by two different brands of Salmonella Vi capsular polysaccharide vaccine (ViCPS).
Setting and Design: Double blind, randomixed (3:1), controlled, parallel, phase III study was conducted at two centers in India to compare the safety and immunologenicity of TypbarTM, the investigational vaccine with an already marketed vaccine 'X', in healthy subjects aged between 12 - 25 years.
Material and Methods: A sample size of 184 subjects was calculated. Subjects were randomly distributed in two groups, immunized with single dose of TypbarTM or Vaccine 'X'. Serum samples were taken before 7 days and 4 weeks after immunization for the determination of antibodies to Vi polysaccharide, by ELISA method. Safety was assessed by physical examination, laboratory parameters before and after vaccination and by monitoring adverse events.
Statistics: The geometric mean antibody titre (GMT) 4 weeks after vaccination was compared from respective pre-vaccination values by Wilcoxon signed rank test. Geometric mean of antibody levels before and after immunization and the ratio between them (Mann-Whitney test), the Seroconversion rates (Z test proportions) and the adverse events (Fisher's exact testand Chi square test), were compared between two groups. P value < 0.005 was considered statistically significant. P values and 95% confidence intervals were estimated in two-tailed fashion.
Results: 153 subjects (Typbar TM = 116 and Vaccine 'X' = 37) were studied. 71.6% (95% CI = 63.4% - 79.8%) and 75.7% (95% CI = 64.9% - 89.5%) were the seroconversion rates with Typbar TM vaccine 'X' respectively.The GMT values for Vi antibodies induced after Typbar TM and vaccine 'X' were 10.23 Typbar TM and 13.46 mg/mL respectively and these values showed high significance when compared to their pre-immunization GMT values ( P < 0.0001) at 95% CI (-10.49 to - 7.19 mg/ML for Typbar TM and -14.69 to - 8.86 mg/mL for vaccine 'X' ). The induction of antibody response appeared to be slightly stronger ( P = 0.032) with vaccine 'X' when compared to that of Typbar TM . This is justifiable as the same group also had high pre-immunization GMT values (P = 0.0021).
Conclusion: The immunogenicty and safety of investigational vaccine Typbar TM was found to be similar to that of already marketed brand of Vi CPS, Vaccine 'X'. The availability of a single dose of vaccine that is safe and effective enhances the prospective for control of typhoid fever.