Pharmacodynamic and safety considerations for influenza vaccine and adjuvant design

ABSTRACT

Introduction

A novel adjuvant evaluation system for safety and immunogenicity is needed. Vaccination is important for infection prevention, for example, from influenza viruses. Adjuvants are considered critical for improving the effectiveness of influenza vaccines. Adjuvant development is an important issue in influenza vaccine design.

Areas covered

A conventional in vivo evaluation method for vaccine safety has been limited in analyzing phenotypic and pathological changes. Therefore, it is difficult to obtain information on the changes at the molecular level. This review aims to explain the recently developed genomics analysis-based vaccine adjuvant safety evaluation tools verified by AddaVax^TM and polyinosinic-polycytidylic acid (poly I:C) using 18 biomarker genes and whole-virion inactivated influenza vaccine as a toxicity control. Genomics analyzes would help provide safety and efficacy information regarding influenza vaccine design by facilitating appropriate adjuvant selection.

Expert opinion

The efficacy and safety profiles of influenza vaccines and adjuvants using genomics technologies provide useful information regarding immunogenicity, which is related to safety and efficacy. This approach provides important information to select appropriate inoculation routes, combinations of vaccine antigens and adjuvants, and dosing amounts. The efficacy of vaccine adjuvant evaluation by genomics analysis should be verified by various studies using various vaccines in the future.

KEYWORDS:

• Adjuvant
• biomarker
• genomics
• immunotoxicity
• influenza vaccine
• preclinical test
• pharmacodynamics
• safety evaluation

Article highlights

• Although the safety of vaccines and adjuvants has been evaluated by classical methods, such as body weight and pathological changes, the development of an evaluation system that is more sensitive and can provide detailed information on toxicity and immunity is desirable.

• Genomics analyses have been shown to be useful in influenza vaccine and adjuvant evaluation.

• Biomarker genes identified from genomics analyses have been shown to be indicators of influenza vaccine and adjuvant immunogenicity, such as blood toxicity and interferon (IFN)-mediated immune response.

• From the verification studies using AddaVaxTM and poly I:C, risk evaluations of toxicity development could be partially predicted and evaluated by simulation using the biomarker gene expression data, suggesting that it may be useful for the design of adjuvanted influenza vaccines.

• Analyses of biomarker gene expression changes by AddaVaxTM and poly I:C have been shown to contribute to the selection of optimal adjuvant candidates for influenza vaccines as well as optimal dosage and inoculation routes.

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This work was supported by the Japan Agency for Medical Research and Development (AMED) under Grant Numbers JP19fk0108051, JP19fk0108100, JP18ak0101071 and Ministry of Education, Culture, Sports, Science and Technology, Japan Society for the Promotion of Science under Grant Number 19K12873.