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Combining Wet and Dry Lab Techniques to Guide the Crystallization of Large Coiled-coil Containing Proteins

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Using crystallography tools to improve vaccine formulations.

Márcia Carvalho de Abreu Fantini¹, Cristiano Luis Pinto Oliveira¹, José Luiz de Souza Lopes¹

¹Physics Institute, University of São Paulo, Rua do Matão 1371, São Paulo, SP 05508-090, Brazil.

|January 21, 2022

Summary

Oral vaccines using porous silica protect antigens from stomach acid, enhancing immunity. Research optimized antigen encapsulation and demonstrated efficacy in mice, paving the way for advanced vaccine delivery.

Keywords:

SAXS XAS imaging oral vaccines porous silica

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Area of Science:

Biomaterials Science
Vaccinology
Nanotechnology

Background:

Oral vaccine delivery faces challenges due to harsh stomach acidity, which degrades protein antigens.
Porous silica matrices offer a protective vehicle for oral vaccine antigens, targeting intestinal immune sites.
Research at the Butantan Institute focuses on optimizing silica-based oral vaccine formulations.

Purpose of the Study:

To summarize advancements in oral vaccine formulations using porous silica matrices.
To detail the optimization of antigen encapsulation and distribution within silica.
To structurally characterize and assess the efficacy of silica-encapsulated antigen complexes.

Main Methods:

Small-angle X-ray scattering (SAXS)
X-ray absorption spectroscopy (XAS)
X-ray phase contrast tomography
Neutron and X-ray imaging
X-ray crystallography
Dynamic light scattering (DLS)
Transmission electron microscopy (TEM)

Main Results:

Optimized antigen encapsulation yield and distribution within porous silica.
Structural characterization of silica-encapsulated hepatitis B virus-like particles and diphtheria anatoxin.
Demonstrated stability of immunogenic complexes across various pH and temperatures.
Validated efficacy of oral immunogenic complexes by comparing antibody responses in mice.

Conclusions:

Porous silica matrices effectively protect encapsulated antigens for oral delivery.
Structural and stability analyses confirm the potential of these vaccine complexes.
The developed oral vaccine formulations show promising immunogenic efficacy in preclinical models.