AAV Gene Therapy Successfully Protects Against Ebola in Mice

Infectious disease researchers have discovered a new method for effectively protecting against and treating Ebola infections. The study, performed in mice, used an adeno-associated virus (AAV) to deliver monoclonal antibody genes against Ebola. Similar viral vector treatments have been used to effectively treat human immunodeficiency virus (HIV) infections.

“Our goal is to make an antibody-based therapy that can protect against all strains of Ebola, and potentially Marburg virus, as well,” says Prof., who, along with PhD student found a new way to fight Ebola. “It would be used to stop the spread of the virus in outbreak situations.”

Traditional monoclonal antibody (mAb) treatments for Ebola are promising but are limited by the resources required for production and the immunity they provide is short-term. Using a viral vector method, anti-Ebola monoclonal antibody genes are delivered to the cell and the cell will produce the antibody and secrete it into the bloodstream to fight an infection. The research team demonstrated that in mice, 100 percent protection was provided against an Ebola infection with a mixture of two different types of antibodies and 83 percent protection was provided with a different antibody cocktail. The gene therapy was shown to provide protection from the disease for five months following administration.

“We are hoping to use this technology in a post-exposure scenario. Let’s say someone has been exposed to Ebola. The idea would be to give them this AAV vector to start producing the antibodies that prevent death, commented the Prof.”

The preliminary findings are promising and the team is moving forward to develop a gene-based therapeutic or vaccine to Ebola or one that can be used to treat other filovirus infections such as Marbug.

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Antibody-producing cells discovered in spleen

Researchers have discovered a type of cells in human spleen that are essential for the production of antibodies, paving way for development of new vaccines to fight meningitis and pneumonia.

Innate lymphoid cells were recently described by the scientific community and represent the first line of immunological defence on our body surfaces, which are constantly exposed to bacteria, such as the intestine or skin.

Now, for the first time their presence and function in human spleen has been described, said Dr Giuliana Magri, member of the research group of B Cell Biology at IMIM (Institut Hospital del Mar d'Investigacions Mediques) in Barcelona, and first author in the paper.

"We have discovered how these cells regulate the innate immune response of a subset of splenic B lymphocytes that are responsible to fight against encapsulated bacteria, causative agents of meningitis or pneumonia," said Magri.

"The current available vaccines against encapsulated bacteria confer only a limited protection in immunodeficient patients, and are too expensive to be implemented in developing countries.

"At the same time, we lack information on the underlying mechanisms that regulate B lymphocytes, which has been a major hurdle in the development of novel vaccine strategies," said Dr Andrea Cerutti, ICREA (Institucio Catalana de Recerca i Estudis Avancats) research professor and leader in the field of B lymphocyte biology.

"This makes the current discovery key in the design of novel more efficient and well-oriented therapies," Cerutti said.

The research involved in vitro studies with isolated cells from human spleen samples and in vivo studies performed with different mice models.

The work explored the function of the innate lymphoid cells in homeostasis, in short, in the absence of any illness, opening the door in the future to study the possible implication of innate lymphoid cells in diverse pathological processes both at the mucosal and systemic level, as well as deepening the understanding of autoimmune and immunodeficient diseases.

The study was published in the journal Nature Immunology.

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