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

Abstract

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.

Keywords::

• administration route
• age
• aluminium adjuvant
• body mass
• ethnicity
• hepatitis A vaccine
• immunogenicity
• injection devices
• intradermal
• intramuscular
• needle length
• pre-existing immunity
• race
• review
• safety
• sex
• subcutaneous
• vaccines
• virosomes

Acknowledgements

Sincere thanks go to M. Royals and S. Herzog for their critical review of the manuscript.

Financial & competing interests disclosure

The author worked from 1994 to 2011 for Crucell Switzerland AG (formerly Berna Biotech/Swiss Serum and Vaccine Institute and now Janssen Pharmaceuticals Inc [part of the pharmacuetical companies of Johnson & Johnson]), the manufacturer of the virosomal hepatitis A vaccine, first as Medical Director and later as Medical Advisor. He currently works as an independent biopharmaceutical consultant. He does not hold any shares in Janssen Pharmaceuticals or Johnson & Johnson and this Review is written independently from these companies. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• A particular vaccine has to be administered via the appropriate route, that is, a route that is optimal regarding immunogenicity, safety and practicability.

• For a correct intradermal, subcutaneous or intramuscular administration of an injectable vaccine, appropriate needle length and size have to be selected.

• Apart from the route itself, there are factors, such as body site, needle length, injection technique, type of antigen, adjuvants, vaccine formulation, age, sex, body mass, race and pre-existing immunity, which can have an impact on the safety and the immunogenicity performance of a vaccine.

• The technical and demographic factors potentially impacting on the performance of a vaccine need to be accounted and controlled for when designing vaccine studies and should be reported in a transparent and standardized way in the publications.