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Nanotechnology could efficiently deliver hepatitis B vaccine

Publicado em 12 julho 2019

Researchers are working on nanotechnology delivering an oral vaccine against hepatitis B

Agroup of international researchers has collaboratively demonstrated how a nanotechnology-based compound can deliver an oral vaccine against hepatitis B to the immune system. When particles containing silica and an antigen combine, despite being of different sizes, they reach the intestine without being eliminated by the acidity of the digestive system. Developing technology which enables oral vaccines to work efficiently remains a considerable effort.

Hepatitis B: a global health problem
Hepatitis B is a potentially life-threatening liver infection that is caused by the hepatitis B virus (HBV). It is a major global health problem.

Such can cause chronic infection and put people at high risk of death from cirrhosis and liver cancer. The virus is usually transmitted from mother to child during birth and delivery; and via contact with blood or other body fluids. The World Health Organization (WHO) estimates that as of 2015, 257 million people were living with chronic hepatitis B infection.

There are two vaccines that protect against hepatitis B:

  • The hepatitis B vaccine protects infants, children, and adults from hepatitis B.
  • The hepatitis A and B combination vaccine protects adults from both hepatitis B and hepatitis A.

Both are given by the intramuscular route. An oral vaccine could provide convenience and access to various populations.

Nanotechnology showing great potential
A compound of nanostructured SBA-15 silica and HBsAg, the hepatitis B surface antigen, was submitted by the research team to different types of X-ray imaging in European laboratories.

The nanostructured silica was conceived by researchers at the University of São Paulo’s Physics Institute (IF-USP) in Brazil. The antigen was created by the Butantan Institute (also located in São Paulo).

The goal of the study was to truly understand how a 22-nanometer-sized antigen binds to silica nanotubes with a diameter of approximately 10 nanometers and a honeycomb-like structure. One nanometer (1 nm) is a billionth of a meter. Studies carried out at USP uncovered the measurements of both the antigen and the silica nanotubes using small-angle X-ray scattering (SAXS), dynamic light scattering (DLS), and transmission electron microscope.

“Despite the size difference, tests [in animals] produced an excellent immune response to the oral vaccine — as good as the injectable form or better,” stated Márcia Fantini, a researcher at IF-USP.

X-ray and neutron imaging was arranged by Heloisa Bordalo, a Brazilian researcher at the University of Copenhagen’s Niels Bohr Institute in Denmark. In collaboration with other researchers in Denmark as well as colleagues in France, Germany, Sweden and Switzerland, Bordalo submitted the compound to small-angle X-ray scattering (SAXS), along with other techniques.

The three-dimensional images generated by these techniques showed that although the antigen did not enter the nanotubes, it was indeed retained in 50 nm macropores between the nanotubes. This protected it from the harsh acidity of the digestive system.

The images also allowed the researchers to gauge the ideal proportion of silica and HBsAg so that the antigen did not form into as mass, hampering the dispersion of the active principle in the patient’s intestine. “The oral and intranasal routes are natural modes of vaccine administration. Nature is the best vaccination agent. However, a vaccine that contains a protein, as in this case, is destroyed by high acidity and its own proteases in passing through the stomach, so it doesn’t reach the immune system, particularly the small intestine,” explained Osvaldo Augusto Sant”Anna, Scientific Leader at Butantan Institute and responsible for development of the HbsAg antigen.

Prior to proceeding to clinical trials, the team will test polymers which can be used to coat the whole structure and increase the medication’s resistance to the human stomach. In animal trials, the formulation proved to be as effective as the injected vaccine (if not more) in delivering the antigen to the intestine, where the immune system can detect it and produce antibodies against the virus.