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.

Is Rerum^® the New Coley's Vaccine?

“…Although supplements are usually meant to be administered through the oral route, in compliance with national rules and regulations and under the direct responsibility of the Therapist, they can also be administered through other routes such as the sublingual or the parenteral. The subcutaneous, intradermal or intramuscular routes of administration are of particular interest since these are efficient ways to prime and modulate the immune system in the context of vaccinations and immunotherapies (Herzog, 2014;Casale and Stokes, 2014) and are consistent with the observation of Prudden who reported excellent results using a combination of oral and subcutaneous administration of bovine cartilage extracts (Prudden, 1985). Using a variety of routes of administration, Rerum ® has been used in the complementary approach to cancer in patients with different malignancies; preliminary results concerning this clinical experience were published in this Journal in 2016 (Schwalb et al, 2016).…”

Comparison of intramuscular and subcutaneous administration of a herpes zoster live-attenuated vaccine in adults aged ≥50 years: A randomised non-inferiority clinical trial

“…The results show that the immune response to IM Zostavax is similar to that to SC Zostavax. In addition, IM administration results in significantly fewer injection-site reactions with a comparable rate of systemic AEs, as has been described for other vaccines [51,52].…”

Evidence calls for practice change in intramuscular injection techniques

“…Manufacturers of vaccines and medications specify the route and injection site based on route and site used in clinical trials, but they rarely state patient weight or gender of the studied population and instrument data such as needle length. [27,28] Another manufacturing problem is the "one size fits all" auto injectors used with medications such as epinephrine. The typical needles used in these injectors are often too short to reach muscle in heavier populations, including women and children.…”

“…[3,21,27] Healthcare facilities should provide a variety of needles with different lengths and gauges, including 2+ inch safety needles. [25] In addition, requiring a clinical assessment of morbidly obese patients by a clinical nurse specialist, nurse practitioner or other specialized nurse before IM injections are given should be a standard within all healthcare facilities.…”