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

Author(s):Show less -

Rasmussen, Martin Kjaerulf ^{[1, 2]} ; Bordallo, Heloisa N. ^{[1, 3]} ; Bordenalli, Marcela Aparecida ^[4] ; Akamatsu, Milena Apetito ^[4] ; Trezena, Aryene Goes ^[4] ; Tino-De-Franco, Milene ^[4] ; Sant'Anna, Osvaldo A. ^[4] ; Martins, Tereza da Silva ^[5] ; de Souza Lopes, Jose Luiz ^[6] ; de Abreu Fantini, Marcia Carvalho ^[6] ; Pinto Oliveira, Cristiano Luis ^[6]

Affiliation

^[1] Univ Copenhagen, Niels Bohr Inst, Copenhagen - Denmark

^[2] Tech Univ Denmark, Dept Hlth Technol, Lyngby - Denmark

^[3] European Spallat Source, Lund - Sweden

^[4] Inst Butantan, Sao Paulo, SP - Brazil

^[5] Univ Fed Sao Paulo, Inst Ciencias Ambientais Quim & Farmaceut, Diadema, SP - Brazil

^[6] Univ Sao Paulo, Inst Fis, Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: Microporous and Mesoporous Materials; v. 312, JAN 2021.
• Web of Science Citations: 0

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. (AU)

• FAPESP's process: 17/17844-8 - Nanostructured silica as a protective vehicle for vaccines and biomolecules
• Grantee: Osvaldo Augusto Brazil Esteves Sant'Anna
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 18/19546-7 - Molecular mechanisms of the binding, insertion, and orientation of antimicrobial peptides in model membranes
• Grantee: Jose Luiz de Souza Lopes
• Support Opportunities: Regular Research Grants