Deconvolution-based deblurring of reconstructed images in photoacoustic/thermoacoustic tomography

Photoacoustic/thermoacoustic tomography is an emerging hybrid imaging modality combining optical/microwave imaging with ultrasound imaging. Here, a k-wave MATLAB toolbox was used to simulate various configurations of excitation pulse shape, width, transducer types, and target object sizes to see their effect on the photoacoustic/thermoacoustic signals. A numerical blood vessel phantom was also used to demonstrate the effect of various excitation pulse waveforms and pulse widths on the reconstructed images. Reconstructed images were blurred due to the broadening of the pressure waves by the excitation pulse width as well as by the limited transducer bandwidth. The blurring increases with increase in pulse width. A deconvolution approach is presented here with Tikhonov regularization to correct the photoacoustic/thermoacoustic signals, which resulted in improved reconstructed images by reducing the blurring effect. It is observed that the reconstructed images remain unaffected by change in pulse widths or pulse shapes, as well as by the limited bandwidth of the ultrasound detectors after the use of the deconvolution technique. (C) 2013 Optical Society of Americ

Multi-dose Formulation Development for a Quadrivalent Human Papillomavirus Virus-Like Particle-Based Vaccine: Part II- Real-time and Accelerated Stability Studies (Dataset)

This is the dataset for the article Multi-dose Formulation Development for a Quadrivalent Human Papillomavirus Virus-Like Particle-Based Vaccine: Part II- Real-time and Accelerated Stability Studies, published in 2022 in the Journal of Pharmaceutical Sciences (Elsevier).This work describes Part 2 of multi-dose formulation development of a Human Papillomavirus (HPV) Virus-Like Particles (VLPs) containing vaccine (see Part 1 in companion paper). Storage stability studies with candidate multi-dose formulations containing individual or combinations of seven different antimicrobial preservatives (APs) were performed with quadrivalent HPV VLP (6, 11, 16, 18) antigens adsorbed to aluminum-salt adjuvant (Alhydrogel®). Real-time (up to two years, 2-8°C) and accelerated (months at 25 and 40°C) stability studies identified eight lead candidates as measured by antigen stability (competitive ELISA employing conformational serotype-specific mAbs), antimicrobial effectiveness (modified European Pharmacopeia assay), total protein content (SDS-PAGE), and AP concentration (RP-UHPLC). The AH-adsorbed HPV18 VLP component was most sensitive to AP-induced destabilization. Optimal quadrivalent antigen storage stability while maintaining antimicrobial effectiveness was observed with 2-phenoxyethanol, benzyl alcohol, chlorobutanol, and 2-phenoxyethanol + benzyl alcohol combination. Interestingly, for single-AP containing multi-dose formulations, this rank-ordering of storage stability did not correlate with previously reported biophysical measurements of AP-induced antigen destabilization. Moreover, other APs (e.g., m-cresol, phenol, parabens) described by others for inclusion in multi-dose HPV VLP formulations showed suboptimal stability. These results suggest that each HPV VLP vaccine candidate (e.g., different serotypes, expression systems, processes, adjuvants) will require customized multi-dose formulation development

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

The development of multi-dose, subunit vaccine formulations can be challenging since antimicrobial preservatives (APs) often destabilize protein antigens. In this work, we evaluated Human Papillomavirus (HPV) Virus-Like Particles (VLPs) to determine if combining different APs used in approved parenteral products, each at lower concentrations than used alone, would maintain both antimicrobial effectiveness and antigen stability. To identify promising AP combinations, two different screening strategies were utilized: (1) empirical one-factor-at-a-time (OFAT) and (2) statistical design-of-experiments (DOE). Seven different APs were employed to screen for two- and three-AP combinations using high-throughput methods for antimicrobial effectiveness (i.e., microbial growth inhibition assay and a modified European Pharmacopeia method) and antigen stability (i.e., serotype-specific mAb binding to conformational epitopes of HPV6, 11, 16 VLPs by ELISA). The OFAT and DOE approaches were complementary, such that initial OFAT results (and associated lessons learned) were subsequently employed to optimize the combinations using DOE. Additional validation experiments confirmed the final selection of top AP-combinations predicted by DOE modeling. Overall, 20 candidate multi-dose formulations containing two- or three-AP combinations were down-selected. As described in Part 2 (companion paper), long-term storage stability profiles of aluminum-adjuvanted, quadrivalent HPV VLP formulations containing these lead candidate AP combinations are compared to single APs

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

Introducing multi-dose formulations of Human Papillomavirus (HPV) vaccines will reduce costs and enable improved global vaccine coverage, especially in low- and middle-income countries. This work describes the development of key analytical methods later utilized for HPV vaccine multi-dose formulation development. First, down-selection of physicochemical methods suitable for multi-dose formulation development of four HPV (6, 11, 16, and 18) Virus-Like Particles (VLPs) adsorbed to an aluminum adjuvant (Alhydrogel®, AH) was performed. The four monovalent AH-adsorbed HPV VLPs were then characterized using these down-selected methods. Second, stability-indicating competitive ELISA assays were developed using HPV serotype-specific neutralizing mAbs, to monitor relative antibody binding profiles of the four AH-adsorbed VLPs during storage. Third, concentration-dependent preservative-induced destabilization of HPV16 VLPs was demonstrated by addition of eight preservatives found in parenterally administered pharmaceuticals and vaccines, as measured by ELISA, dynamic light scattering, and differential scanning calorimetry. Finally, preservative stability and effectiveness in the presence of vaccine components were evaluated using a combination of RP-UHPLC, a microbial growth inhibition assay, and a modified version of the European Pharmacopoeia assay (Ph. Eur. 5.1.3). Results are discussed in terms of analytical challenges encountered to identify and develop high-throughput methods that facilitate multi-dose formulation development of aluminum-adjuvanted protein-based vaccine candidates