Factors associated with vaccine reactogenicity in school aged children and young adults following administration of two protein-based vaccines

Abstract

Aim To identify or exclude factors associated with injection site reactions following immunisation. Methods Literature review identifying key factors of gender, psychological stress, and exercise and injection technique. Study conducted involving secondary analyses of existing data from a clinical trial of outer membrane vesicle meningococcal (OMV) vaccines in children aged eight to 12 years including examination of factors associated with perceived pain at the time of injection, followed by a randomised trial of three injection techniques used to deliver the quadrivalent human papillomavirus vaccine in females aged 14-45 years and males aged 14-26 years. Data collected included stress variables and blood samples for evaluation of cytokines. Findings In the first study vaccinator was the variable with largest effect on reactogenicity outcomes of injection site pain, erythema and induration. Ethnicity had an effect on injection site pain and erythema. Body mass index was associated with injection site pain. Baseline antibody did not affect injection site reactions but reactogenicity effected antibody levels measured after dose two. Perceived pain on injection was most strongly effected by vaccinator and vaccine formulation. These outcomes informed the design for the prospective study. This trial found the three injection techniques did not affect injection site reactogenicity. Females tended to experience more reactogenicity. Perceived stress, social support and atopy were not associated with reactogenicity outcomes and exercise showed little effect. No cytokine functional groups nor individual cytokines were associated with reactogenicity outcomes. No variables, including injection technique, were associated with wide variation in perceived pain on injection. Case-by-case observational data suggest some variations in anatomical site may be important. Conclusions This thesis demonstrated factors that can ameliorate both reactogenicity and pain on injection. Injection technique plays an important role in both reactogenicity and perceived pain on injection following OMV vaccines. Why vaccinator effects on pain on injection was not elucidated from the trial but anatomical site may be a factor, which has implications for vaccinator education. Ethnic differences in injection site reactions requires further research. Calling reactogenicity an adverse event may be a misnomer since it correlates positively with antibody response, a finding which could improve confidence in immunisation.