Effect of vaccine administration modality on immunogenicity and efficacy

Abstract

The many factors impacting the efficacy of a vaccine can be broadly divided into three categories: features of the vaccine itself, including immunogen design, vaccine type, formulation, adjuvant and dosing; individual variations among vaccine recipients and vaccine administration-related parameters. While much literature exists related to vaccines, and recently systems biology has started to dissect the impact of individual subject variation on vaccine efficacy, few studies have focused on the role of vaccine administration-related parameters on vaccine efficacy. Parenteral and mucosal vaccinations are traditional approaches for licensed vaccines; novel vaccine delivery approaches, including needless injection and adjuvant formulations, are being developed to further improve vaccine safety and efficacy. This review provides a brief summary of vaccine administration-related factors, including vaccination approach, delivery route and method of administration, to gain a better understanding of their potential impact on the safety and immunogenicity of candidate vaccines.

Keywords:

• administration
• efficacy
• immunogenicity
• vaccination
• vaccine
• vaccine delivery

Financial & competing interests disclosure

This study was supported in part with grants from the Priority Academic Program Development of Jiangsu Higher Education Institutions (JX10231801), NIH Grants AI-087191, AI-082274, AI-082676 and Bill and Melinda Gates Foundation Grant OPP1033112. The authors have 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.

Key issues

• Overall, although vaccine administration-related factors may not be physically part of a vaccine, the immunogenicity and safety of a vaccine can be greatly impacted by vaccination administration factors, including vaccination schedules and methods.

• Most vaccines require multiple prime-boost immunizations in order to achieve adequate protective immunity. However, other vaccines may require fewer or more immunizations in order to achieve protective immunity and optimal intervals between immunizations appear to differ among these different vaccines.

• Although conventional intramuscular injection has been used and recommended for many licensed vaccines in the market, the vaccine efficacy and safety profile can be further improved by using an alternative route of vaccine delivery (including subcutaneous and intradermal injection and needle-free injection) or by taking other administration factors into account, such as inoculation sites and needle length.

• Targeting mucosal compartments to induce protective immunity at both the mucosal site and the systemic level remains a great challenge. Investigation and understanding of the best way to incorporate the mucosal immunizations into prime-boost vaccination regimens in combination with parenteral vaccination to enhance both mucosal and systemic immune responses is critical.

• With the development of novel vaccine delivery methods, including needle-free injection, microneedle delivery, topical application and ultrasonication, safety profile and vaccine delivery efficiency will need to be evaluated individually and in combination with other vaccination approaches.