Assessing the efficiency of SBA-15 as a nanocarrier for diphtheria anatoxin

Martin Kjærulf Rasmussen, Heloisa N. Bordallo, Marcela Aparecida Bordenalli, Milena Apetito Akamatsu, Aryene Góes Trezena, Milene Tino-De-Franco, Osvaldo A. Sant'Anna, Tereza da Silva Martins, José Luiz de Souza Lopes, Márcia Carvalho de Abreu Fantini, Cristiano Luis Pinto Oliveira

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

SBA-15 ordered mesoporous silica can be considered a promising inorganic nanocarrier with emerging potential as an oral vaccine adjuvant. In this study, we investigated its application in the encapsulation of the diphtheria anatoxin (dANA). We observed a considerable preservation of dANA secondary and tertiary structures, even after the drying process by means of Circular Dichroism (CD) and fluorescence spectroscopies. Antigen loading was assessed at a number of different ratios of adjuvant-to-antigen using a combination of nitrogen adsorption porosimetry and Small Angle X-ray Scattering (SAXS). Our data showed that the mass ratio of 1:10 (dANA:SBA-15) is recommended for total encapsulation of dANA in the mesopores, considering that at this relative mass concentration antigen clustering was avoided, which is deleterious effect for immunization purposes. dANA release in mimetic intestine fluid, at a pH equal to 6.8, was followed by in-situ SAXS measurements and shown to be slow, being more pronounced after 6 h and continuous up to 35 h. Finally, the immunogenic complex was tested in isogenic Balb C mice by oral and subcutaneous immunization routes, including a comparison with the only permitted adjuvant for human use, aluminum hydroxide. A higher antibody titer was obtained by subcutaneous and oral administration routes using SBA-15 as the vehicle of dANA, compared with the conventional aluminum hydroxide, demonstrating the viability to use this ordered mesoporous silica in the formulation of oral vaccines, as already proved for the Virus Like Particles (VLP) Hepatitis B (HBsAg) case.
Original languageEnglish
Article number110763
JournalMicroporous and mesoporous materials
Volume312
Number of pages9
ISSN1387-1811
DOIs
Publication statusPublished - 2021

Keywords

  • Diphtheria anatoxin
  • Ordered mesoporous silica
  • Oral vaccine

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