Influence of parenteral administration routes and additional factors on vaccine safety and immunogenicity: a review of recent literature.

Vaccines have to be administered via an appropriate route, i.e. a route, which is optimal regarding safety, immunogenicity and practicability. In addition, there are factors, such as body site, needle length, injection technique, depth of injection, type of antigen, vaccine formulation, adjuvants, age, sex, race/ethnicity, body mass, and pre-existing immunity, which can have an impact on the reactogenicity and tolerability and/or on the immunogenicity of a given vaccine. For parenteral vaccine administration there are currently three routes licensed: intramuscular, subcutaneous and intradermal, either by using conventional hypodermic needles or by using alternative or needle-free injection devices. The factors potentially impacting on the 'performance' of a given route of administration, as reported in recent literature, are outlined and discussed in view of their importance. These factors need to be accounted and controlled for when designing vaccine studies and should be reported in a transparent and standardised way in publications.