From the Fahmy Lab, Vaccine Makes Use of "Artificial Bacteria"


Today, commercially available vaccines come in a solution with three main components: the antigen (the part of the pathogen that activates the immune system) the adjuvant (which further boosts the immune system) and the carrier. One flaw of this form of vaccine is that the body's immune cells may not receive all three of these, which diminishes the fight against the infection.

With what they call an "artificial bacteria," Yale researchers have developed a nanoparticle-based vaccine designed to deliver all three components directly to the immune cells. The results are published online in Biomaterials.

Prof. Tarek Fahmy, corresponding author of the study, said they designed the nanoparticle to alert the body's toll-like receptors (TLRs) – a kind of protein that activates the body's immune response once they recognize invading pathogens. There are 11 TLRs found in humans, each one specializing in recognizing different patterns in pathogens; Fahmy's nanoparticle focuses on two of them. One is TLR4, which recognizes lipopolysaccharide (LPS), found in Gram-negative bacteria, which are particularly resistant to drug treatment. The other is TLR9, which recognizes a type of harmful DNA found in bacteria.

"We looked at what happens when you put something recognized by TLR9 on the inside - like a particular type of DNA - and then put on the surface of these particles something recognized by TLR 4 like LPS," said Fahmy, who teaches biomedical engineering and immunobiology. "The result was that you have something that looked to the immune system like a bacteria on the outside and something like a bacteria on the inside. Once the immune system recognizes and tries to eliminate it, it would also take in the vaccine, the antigen, and develop a very healthy immune response."

The particle, he says, is like a Trojan horse. The key is that the DNA and the LPS are delivered together.

"It's a vehicle that has the immune stimulatory component, and the antigen and the carrier – it's all in the same package," he said. "The same immune cell that sees them will be responsive only to that specific antigen."