Using crystallography tools to improve vaccine formulations

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  • Marcia Carvalho de Abreu Fantini
  • Cristiano Luis Pinto Oliveira
  • Jose Luiz de Souza Lopes
  • Tereza da Silva Martins
  • Milena Apetito Akamatsu
  • Aryene Goes Trezena
  • Milene Tino-De-Franco
  • Viviane Fongaro Botosso
  • Osvaldo Augusto Brazil Esteves Sant'Anna
  • Nikolay Kardjilov
  • Rasmussen, Martin Kaag
  • Nunes Bordallo, Heloisa

This article summarizes developments attained in oral vaccine formulations based on the encapsulation of antigen proteins inside porous silica matrices. These vaccine vehicles show great efficacy in protecting the proteins from the harsh acidic stomach medium, allowing the Peyer's patches in the small intestine to be reached and consequently enhancing immunity. Focusing on the pioneering research conducted at the Butantan Institute in Brazil, the optimization of the antigen encapsulation yield is reported, as well as their distribution inside the meso- and macroporous network of the porous silica. As the development of vaccines requires proper inclusion of antigens in the antibody cells, X-ray crystallography is one of the most commonly used techniques to unveil the structure of antibody-combining sites with protein antigens. Thus structural characterization and modelling of pure antigen structures, showing different dimensions, as well as their complexes, such as silica with encapsulated hepatitis B virus-like particles and diphtheria anatoxin, were performed using small-angle X-ray scattering, X-ray absorption spectroscopy, X-ray phase contrast tomography, and neutron and X-ray imaging. By combining crystallography with dynamic light scattering and transmission electron microscopy, a clearer picture of the proposed vaccine complexes is shown. Additionally, the stability of the immunogenic complex at different pH values and temperatures was checked and the efficacy of the proposed oral immunogenic complex was demonstrated. The latter was obtained by comparing the antibodies in mice with variable high and low antibody responses.

Original languageEnglish
JournalIUCrJ
Volume9
Pages (from-to)11-20
Number of pages14
ISSN2052-2525
DOIs
Publication statusPublished - 1 Jan 2022

    Research areas

  • oral vaccines, porous silica, SAXS, XAS, imaging, MESOPOROUS SILICA NANOPARTICLES, ADJUVANT, SBA-15, ANTIGEN, SIZE

ID: 301614256