Immunogenicity and safety of combined immunization of healthy children with varicella vaccine and measles, mumps and rubella vaccine
Objective 
To evaluate the immunogenicity and safety of combined vaccination of healthy children with varicella vaccine and measles, mumps and rubella (MMR) vaccine and to provide a guidance for reasonable arrangement of immunization schedule. 
 
 
Methods 
Healthy and eligible children aged 17-24 months were recruited and divided into three groups. Subjects in the three groups were respectively immunized with varicella or MMR vaccine alone or in combination. Blood samples were collected from the subjects before and 35-42 days after vaccination for the detection of seroprevalence. Subjects were also asked to fill in safety observation forms 30 minutes, 24, 48, 72 hours and 7, 14, 30 days after vaccination. Each group contained no less than 100 subjects. Statistical analysis was conducted by using χ2 test, Fisher's exact test and non-parametric test. 
 
 
Results 
A total of 445 subjects completed the serologic detection and 450 completed the safety observation. Seropositive rates and geometric mean titers (or concentrations) (GMT or GMC) of antibodies against varicella, measles, mumps and rubella were all significantly increased after immunizing the subjects of different groups with corresponding vaccination strategies. The seropositive rates, seroconversion rates and antibody levels of the combined immunization group were higher than those of the other two groups. Subjects in the MMR group who were negative for anti-mumps antibody before vaccination showed significantly higher GMC of anti-mumps antibody than those in combined immunization group. Subjects in MMR group with positive results of anti-rubella antibody showed significantly higher GMC of anti-rubella antibody than those in combined immunization group. Adverse reactions were reported in 23 subjects with a rate of 5.11%. All of the 23 cases were manifested as moderate or severe fever and one was accompanied with rash. No significant differences in the incidence rates of adverse reactions were observed between three groups. 
 
 
Conclusion 
Immunizing children aged 18-23 months with varicella vaccine or MMR vaccine alone or in combination could significantly increase the seropositive rates and antibody levels. Adverse reactions caused by the combined immunization were mainly fever and rash. No significant difference in the incidence rates was found between the combined vaccination group and the other two groups. The titers of antibody against varicella in subjects immunized with both varicella and MMR vaccines were significantly higher than those immunized with varicella vaccine alone. No significant difference in the levels of antibodies against measles, rubella and mumps was found between the MMR vaccination group and the combined vaccination group. However, considering the limitation of this study, these results still need further study for verification. 
 
 
Key words: 
Varicella vaccine; Measles, mumps and rubella (MMR) vaccine; Combined immunization; Immunogenicity; Safety