Ehrlichia Infection Blocked with Novel Nanobody

Ohio State University researchers have created nanobodies intended to target a protein that makes E. chaffeensis bacteria particularly infectious. Their experiments showed that one specific nanobody they created in the lab could inhibit infection by blocking three ways the protein enables the bacteria to hijack immune cells. Their findings will be published in PNAS. 

"Infected cells normally would commit suicide by apoptosis to kill the bacteria inside. But these bacteria block apoptosis and keep the cell alive so they can multiply hundreds of times very rapidly and then kill the host cell," lead researcker Yasuko Rikihisa said. The team had previously identified which proteins help the bacteria block programmed cell death. 

For their most recent study, the researchers synthesized one of these proteins, called Etf-1, to make a vaccine-style agent that they used to immunize a llama. Camels, llamas and alpacas are known to produce single-chain antibodies that include a large antigen binding site on the tip. The team snipped apart segments of that binding site to create a library of nanobodies with potential to function as antibodies that recognize and attach to the Etf-1 protein and stop E. chaffeensis infection.

"They function similarly to our own antibodies, but they're tiny, tiny nano-antibodies," Rikihisa said. "Because they are small, they get into nooks and crannies and recognize antigens much more effectively.

After screening the candidates for their effectiveness, the researchers landed on a single nanobody that was able to attach to Etf-1 in cell cultures and inhibited three of its functions. With this study providing the proof of principle that nanobodies can inhibit  E. chaffeensis infection by targeting a single protein, Rikihisa said there are multiple additional targets that could provide even more protection with nanobodies delivered alone or in combination. She also said the concept is broadly applicable to other intracellular diseases.