A Rational, Systematic Approach for the Development of Vaccine Formulations

Abstract

Abstract. With the continuous emergence of new infectious diseases and new strains of current diseases, such as the novel H1N1 influenza in 2009, in combination with expanding competition in the vaccine marketplace, the pressure to develop vaccine formulations right the first time is increasing. As vaccines are complex, costly, and have high risk associated with their development, it is necessary to maximize the potential for development of a successful formulation quickly. To accomplish this goal, the historical empirical approach to formulation development needs to be updated with a rational, systematic approach allowing for more rapid development of safe, efficacious, and stable vaccine formulations. The main components to this approach are biophysical characterization of the antigen, evaluation of stabilizers, investigation of antigen interactions with adjuvants, evaluation of product contact materials, and monitoring stability both in real time and under accelerated conditions. An overview of investigations performed for each of these components of formulation development is discussed. The information gained in these studies is valuable in forming the base of knowledge for the design of a robust formulation. With the use of continually advancing technology in combination with maintaining a rational, systematic approach to formulation development, there is a great increase in the probability of successfully developing a safe, effective, and stable vaccine formulation.

The two faces of His‐tag: Immune response versus ease of protein purification

“…Although the conformation of a protein antigen in a vaccine formulation is recognized to be critical for generating an appropriate immune response [11], it is not generally known exactly which aspects of a protein antigen's conformation must be maintained in order to retain full potency of the vaccine. The His-tag dependent immune responses to a potential vaccine antigen observed by Khan et al [7] emphasize that subtle alterations in protein structure may influence their antigenicity.…”

Established and advanced adjuvants in vaccines' formulation: Mineral adsorbents, nanoparticulate carriers and microneedle delivery systems

“…During storage at room temperature, aluminum adjuvants become more ordered due to deprotonation and dehydration. Once the physical properties of the adjuvant are known, an antigen interaction with the adjuvant can be determined (17). As a general rule, the antigen should be adsorbed onto the adjuvant prior to immunization and the adsorption should be carefully monitored (7).…”

“…Owing to the complex structure of antigens, it is not surprising that a number of attractive mechanisms may contribute to their adsorption (11). These mechanisms include electrostatic attraction, hydrogen bonding, hydrophobic interactions, ligand exchange and van der Waals forces (11,17), while each binding force in a given antigen-adjuvant combination depends on the nature of the antigen and the chemical environment: pH, ionic strength, presence of surfactants, etc. (7).…”

Particulate inorganic adjuvants: recent developments and future outlook

“…One reason for this might be that antigens are thought to be less stable when adsorbed to alum than when in solution[63] because in the former setting there is an increased susceptibility to physical and chemical degradation [64,65]. Two recent reviews discuss these challenges in detail and posit future formulation strategies to maximise vaccine efficacy [66,67]…”

“…[64,65] Two recent reviews discuss these challenges in detail and posit future formulation strategies to maximise vaccine efficacy. [66,67]…”