February 08, 2018 -- Researchers are working on new generations of oral vaccines for infectious diseases. But to be effective, oral vaccines must survive digestion and reach immune cells within the intestinal wall. As a step in this direction, UC San Diego nanoengineering researchers have developed oral vaccines powered by micromotors that target the mucus layer of the intestine.
The work appears in the ACS journal Nano Letters. It’s a collaboration between the labs of nanoengineering professors Joseph Wang and Liangfang Zhang at the UC San Diego Jacobs School of Engineering.
The lack of needles is one reason oral vaccines are attractive. Another reason: oral vaccines can generate a broad immune response by stimulating immune cells within the mucus layer of the intestine to produce a special class of antibody called immunoglobulin A (IgA).
The NanoLetters paper documents the team’s efforts to use magnesium particles as tiny motors to deliver an oral vaccine against the bacterial pathogen Staphylococcus aureus. When coated over most of their surfaces with titanium dioxide, magnesium microparticles use water as fuel to generate hydrogen bubbles that power their propulsion.
To develop the oral vaccine, the researchers coated magnesium micromotors with red blood cell membranes that displayed the Staphylococcal α-toxin, along with a layer of chitosan to help them stick to the intestinal mucus. Then, they added an enteric coating that protects drugs from the acidic conditions of the stomach.
The micromotors safely passed through the stomach to the intestine, at which point the enteric coating dissolved, activating the motors. Imaging of mice that had been given the vaccine showed that the micromotors accumulated in the intestinal wall much better than non-motorized particles. The micromotors also stimulated the production of about ten times more IgA antibodies against the Staphylococcal α-toxin than the static particles.
Paper title: Biomimetic Micromotor Enables Active Delivery of Antigens for Oral Vaccination
Authors: Xiaoli Wei, Mara Beltrán-Gastélum, Emil Karshalev, Berta Esteban-Fernández de Ávila, Jiarong Zhou, Danni Ran, Pavimol Angsantikul, Ronnie H. Fang, Joseph Wang, and Liangfang Zhang / Department of NanoEngineering and Chemical Engineering Program, University of California San Diego Jacobs School of Engineering
Funders: This work was supported by the Defense Threat Reduction Agency Joint Science and Technology Office for Chemical and Biological Defense (HDTRA1-18-1-0014 and HDTRA1-13-1-0002). M.B.-G. acknowledges a postdoctoral fellowship from Consejo Nacional de Ciencia y Tecnología (CONACyT). E.K. acknowledges support from the Charles Lee Powell Foundation. J.Z. acknowledges support from a National Institutes of Health 5T32CA153915 training grant from the National Cancer Institute.
Press release source: American Chemical Society (ACS)