Physicochemical and functional characterization of vaccine antigens and adjuvants

Abstract

As novel vaccine antigens and adjuvants are being tested in humans, understanding of critical quality attributes essential for eliciting optimal vaccine response and vaccine antigen–adjuvant interactions is pivotal for vaccine safety and eliciting ‘protective’ immune responses. Therefore, the efforts to better characterize and evaluate vaccine antigen and antigen–adjuvant drug products need to begin very early during the discovery and development phase. In this review, we discuss the importance of characterization of physicochemical and functional properties in vaccine antigen, adjuvant and the final antigen–adjuvant drug product and emphasize the greater need for more extensive understanding of vaccine antigen–adjuvant interactions. We highlight the key parameters and quality attributes that are critical to measure during preclinical and clinical testing of the vaccine and discuss in some detail the technologies, and their limitations, used in analyzing the key physicochemical and functional attributes of vaccine antigen and antigen–adjuvant drug product.

Keywords::

• analytical assays
• antigen–adjuvant interactions
• vaccine
• vaccine adjuvant
• vaccine antigen
• vaccine characterization

Financial & competing interests disclosure

AK Dey, P Malyala and M Singh are employees at Novartis Vaccines and shareholders of Novartis. Other than MF59^®, Novartis Vaccines’ proprietary adjuvant, the authors have no financial involvement with the subject matter or materials discussed in the manuscript. 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.

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

Key issues

• Despite significant technological advances, vaccine drug products still continue to be less well-characterized due to complex physicochemical interactions of antigen–adjuvant formulations in addition to limit of detection and limit of quantification challenges of the current techniques when applied to vaccine formulations where doses are in microgram concentrations.

• A systematic approach toward understanding of physicochemical and functional vaccine antigen-specific attributes that contributes to vaccine efficacy is essential to design next-generation tailored vaccines.

• Adjuvants are critical in potentiating and tailoring immune response of modern vaccines, hence more rigorous antigen–adjuvant combination characterization is warranted.

• Adopting a systematic and rational approach for antigen and drug product characterization, following a quality by design principle, will contribute to generation of robust, well-characterized, safe and efficacious vaccines.

• The majority of the approaches and challenges applicable to biologicals, therapeutic proteins, and sub-visible particle characterization and stability study principles are applicable to vaccine antigen and antigen–adjuvant analysis and hence should be used.