Protecting against RSV
A research paper published in ScienceImmunology on 17 May 2019, suggests there may be a new way to protect at-risk patients from potentially deadly viruses using engineered immune cells. For decades scientists have been searching for vaccinations for diseases including respiratory syncytial virus (RSV), the influenza virus, HIV and Epstein-Barr. All of these infections pose huge risks to certain groups of people, particularly children and older people.
Gene-editing technology against RSV
RSV is one of the most common viruses that affects children all around the world. Over recent decades, it’s become clear that it poses a significant threat to some adults too, particularly the elderly.
Globally, there are more than 33 million recorded episodes of acute lower respiratory infection associated with RSV in children under five. This results in a minimum of 3.2 million hospital admissions, and around 59,600 hospital deaths. For children aged under five. RSV is more of a threat than flu or other respiratory pathogens.
Vaccines generally contain minute particles of the virus they treat. These particles stimulate the patient’s immune system and cause it to produce antibodies that work against the targeted pathogen. While research has been ongoing for many years to find a vaccination for RSV, and other viruses, it hasn’t yet been possible.
Engineering B cells to boost antibodies
A research team behind the new study is being led by Dr Justin Taylor at the Fred Hutchinson Cancer Research Centre in Seattle, US. The team engineered a type of white blood cell called ‘B cells’ or ‘B lymphocytes’ to express antibodies to target RSV.
The B cells were engineered using clustered regularly interspaced palindromic repeats (CRISPR)-Cas9. This is a gene-editing technology that makes it possible to correct errors in the genome and switch genes in cells and organisms on or off cheaply, quickly and relatively easily. It has already repaired defective DNA in mice and cured their genetic disorders. Treating infectious diseases like HIV and RSV are other clinical applications of this technology.
In this case, the engineered B cells were injected into mice, which lacked T and B cells. The mice were subsequently shown to be protected against RSV when exposed, even in mice with compromised immune systems. They were protected for at least 86 days, while the control mice in the experiment quickly became seriously ill with the virus.
The gene-editing technology removed the gene associate with the antibody in the B cells before a viral vector was used to replace it with a gene encoding for the anti-RSV antibody. This allows the engineered cells to make enough of the antibody to protect the cells.
Potential use against other viruses
This approach may also work on other viruses, such as HIV and other deadly viruses that have no effective vaccine. Various studies show it is possible to engineer genes in mice and humans to express enough antibodies to protect against different viruses.
While some argue that immune cell-based therapies are too expensive, and may therefore be impractical, the findings of this research are significant. The researchers showed “specific and efficient engineering of cells to produce multiple potent antiviral antibodies.”
The authors of the research report write: “Although the use of antibody-producing primary B cells in adoptive cellular therapy has lagged behind that of other cell types, there has recently been a wave of innovation in this area that paves the way for future clinical trials.”
Report: Moffett, H.F. et al. B cells engineered to express pathogen-specific antibodies protect against infection. Science Immunology (2019). DOI: 10.1126/sciimmunol.aax0644
About Garth Rapeport
Garth Rapeport is CEO and co-founder of Pulmocide Ltd, which focuses on developing inhaled antifungal medicines to treat life-threatening lung conditions. These include Invasive Aspergillus, RSV (respiratory syncytial virus), asthma and cystic fibrosis. Garth is also Visiting Professor at the National Heart & Lung Institute, Imperial College School of Medicine.
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