Post-immunisation fever and the antibody response to measles-containing vaccines

Fever is a common adverse event following measles vaccination, more frequent among older children and those receiving Measles-Mumps-Rubella-Varicella vaccine vs. Measles-Mumps-Rubella vaccine, two factors associated with a better antibody response. However, the role of fever in the immunogenicity of measles-containing vaccines (MCV) is unclear. We performed a post-hoc pooled analysis of data of 5 216 11 to 22 month-old children receiving MCV from 2004 to 2012 in Europe and USA to evaluate the association between post-immunisation fever and antibody response, measured by geometric mean concentrations (GMCs). We further evaluated fever as an effect modifier or a mediator in the associations between the type of MCV or the age at first vaccination and vaccine immunogenicity. After the first dose, fever was associated with 60% higher GMCs (95% CI 1.51-1.68). For children vaccinated at ≥12 months, the fever did not modify and minimally mediated (2% to 3%) the association between age and antibody response. Fever mediated 18% of the association between type of MCV and GMCs. In a model including fever, age and type of vaccine, fever was the strongest predictor of GMCs. These results suggest that fever is associated with a stronger measles antibody response independently of age and type of MCV.