Structure and compositional analysis of aluminum oxyhydroxide adsorbed pertussis vaccine
| Autor: | Sasmit S. Deshmukh, Wayne Williams, Jessie Rose Payne, Manjit Haer, Kristen Kalbfleisch, Ibrahim Durowoju, Marina Kirkitadze, Jessica Duprez |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
medicine.medical_treatment
Biophysics Pertussis toxin Biochemistry 03 medical and health sciences 0302 clinical medicine Adsorption Pertussis Structural Biology Genetics medicine Thermal stability TLR agonist Fourier transform infrared spectroscopy Protein secondary structure Particle sizing 030304 developmental biology ComputingMethodologies_COMPUTERGRAPHICS 0303 health sciences Chemistry Tdap vaccines Computer Science Applications Crystallography FTIR 030220 oncology & carcinogenesis Pertussis vaccine Particle size Adjuvant PAT TP248.13-248.65 medicine.drug Research Article Biotechnology |
| Zdroj: | Computational and Structural Biotechnology Journal, Vol 19, Iss, Pp 439-447 (2021) Computational and Structural Biotechnology Journal |
| ISSN: | 2001-0370 |
| Popis: | Graphical abstract Purpose The goal of this study was to characterize an acellular pertussis vaccine (Tdap) containing genetically modified pertussis toxin (gdPT) and TLR agonist adsorbed to AlOOH adjuvant. Methods Several analytical tools including nanoDSF, FTIR, and LD were used to examine the conformation of novel gdPT and the composition of AlOOH adjuvant formulations adsorbed to pertussis vaccine. Results DLS particle size results were 9.3 nm and 320 nm for gdPT. For pertussis toxoid (PT), the DLS particle size results were larger at ~440 nm. After adsorption to AlOOH, which was driven by the protein antigen, the size distribution ranged from 3.5 to 22 µm. Two thermal transitions were observed by DSC for gdPT at 70 °C and 102 °C. The main thermal transition was confirmed to be at 72 °C by nanoDSF. All three vaccine formulations showed one thermal transition: Tdap-AlOOH had a thermal transition of 74.6 °C, Tdap-E6020-AlOOH had a thermal transition at 74.2 °C, and Tdap-CpG-AlOOH had a thermal transition at 77.0 °C. Analysis of pertussis toxin (PTx) and gdPT was also performed by FTIR spectroscopy for the purpose of comparison. The second derivative of the FTIR spectra showed an additional feature for PTx at 1685 cm−1 compared to gdPT. The antigen’s amide I and II regions were largely unchanged after adsorption to AlOOH adjuvant as shown by FTIR, suggesting that there were no significant changes in the secondary structure. Conclusion gdPT conformation was successfully characterized using an array of analytical methods. All three Tdap formulations have similar thermal stability as shown by nanoDSF, similar size distribution as shown by LD, and similar overall secondary structure as shown by FTIR. In-line particle sizing and IR can be used as in-process characterization tools to monitor consistency of adsorbed vaccine and to confirm product identity. |
| Databáze: | OpenAIRE |
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