Interaction of Aluminum-adjuvanted Recombinant P[4] Protein Antigen With Preservatives: Storage Stability and Backbone Flexibility Studies

Formulation development and comparability studies with an aluminum-salt adjuvanted SARS-CoV-2 spike ferritin nanoparticle vaccine antigen produced from two different cell lines

“…Agarwal et al (2020) examined the P[ 8 ] antigen of a subunit rotavirus vaccine candidate by DSC and no notable changes in Tm or ΔH′ values were observed after AH adsorption, however, a ~5°C reduction of the Tonset values was observed [ 23 ]. Interestingly, HX-MS analysis of the closely related AH-adsorbed P(4)antigen revealed site-specific structural alterations in the key epitope involved in the binding of a P(4) specific mAb [ 51 ]. As another example, Bajoria et al (2022) performed DSC analysis of a SARS-CoV-2 receptor binding domain (RBD) vaccine candidate before and after adsorption to AH, and results demonstrated a large reduction in both Tm (~12°C) and ΔH′ values [ 52 ].…”

Analytical and Preformulation Characterization Studies of Human Papillomavirus Virus-Like Particles to Enable Quadrivalent Multi-Dose Vaccine Formulation Development

“…DSC has not only been widely used to evaluate preservative effects on the conformational stability of recombinant proteins but it can also be utilized to evaluate such effects for in-solution and AH-adsorbed subunit vaccine antigens. 28,43,69,72 In this work, we used DSC to evaluate the effects of preservatives on the stability of in-solution and AH-adsorbed HPV16 VLPs at pharmaceutically relevant concentrations that inhibit microbial growth. In addition, DSC analysis was also performed at a common concentration to evaluate trends between the physicochemical properties of the preservatives and their effects on conformational stability.…”

Multi-Dose Formulation Development for a Quadrivalent Human Papillomavirus Virus-Like Particle-Based Vaccine: Part I - Screening of Preservative Combinations

“…3 The incompatibility of APs with recombinant protein-based therapeutics and vaccines has been widely reported. [4][5][6][7] For example, thimerosal (TH), which is a commonly used vaccine preservative, is incompatible with HPV VLP antigens leading to a loss of in vitro antigenicity and in vivo immunogenicity. [8][9][10] Thus, there is an ongoing need to identify multi-dose HPV vaccine formulations and to determine if the limited reports available to date using alternative APs are generally applicable to HPV VLPs of varying serotypes and/or VLPs produced from different expression systems and processes.…”

“…[8][9][10] Thus, there is an ongoing need to identify multi-dose HPV vaccine formulations and to determine if the limited reports available to date using alternative APs are generally applicable to HPV VLPs of varying serotypes and/or VLPs produced from different expression systems and processes. 8,11,12 Since APs at their "in-use" concentration ranges (i.e., levels found in approved parenteral products) often destabilize recombinant protein candidates (e.g., monoclonal antibodies (mAbs) and vaccine antigens), 4,6,7,13 one alternate approach to potentially maintain both protein antigen stability and antimicrobial effectiveness is to combine multiple APs at varying concentrations. [13][14][15][16] In this work, we evaluated if such a strategy could be applied to develop a stable multi-dose formulation for a multivalent HPV VLP-based vaccine.…”