Digitally colored electron micrograph shows monkeypox virus infection in marmoset liver cell from previously published study. Viral particles are shown in red, mitochondria in green, lipid in yellow, nuclei in teal, and cell cytoplasm in blue. Dashed inset of viral particles (upper right) enlarged to show detail (lower right). Credit: USAMRIID/Mucker et al., Janice Williams, Ph.D.
The development of the COVID-19 vaccine showed how messenger RNA (mRNA) can be used as a tool to fight disease-causing viruses. The groundwork for mRNA vaccines was laid through years of previous research, including projects funded through the Defense Advanced Research Projects Agency’s ADEPT: PROTECT program, which is aimed at early detection and rapid response to disease outbreaks. Now, a new ADEPT: PROTECT program study conducted at the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), in collaboration with biopharmaceutical company CureVac, has shown how mRNA could be used to treat infectious diseases in addition to preventing them, by enabling the production of therapeutic antibodies against infections like smallpox and monkeypox.
In contrast to the COVID-19 mRNA vaccine, which encodes part of the SARS-CoV-2 spike protein in order to “teach” the immune system to fight the virus, the mRNA technology used by the USAMRIID researchers encodes specific monoclonal antibodies (mAbs) that are known to counteract poxviruses. In this study, the researcher administered unmodified mRNA encoding the c8A, c6C and c7D11 mAbs, to rabbits; the mRNA was encapsulated in lipid nanoparticles and administered through separate intramuscular injections for each antibody. Enzyme-linked immunosorbent assays (ELISA) and extracellular virus neutralization assays were performed to assess the levels of biologically active antibodies in the animals’ serum after injection.
The researchers found that when all three mRNAs were administered to the same rabbit, all three mAbs were shown to be circulating in the animal’s blood within just one day. The proof-of-concept study successfully demonstrated how mRNA could be delivered and used to express functional antibodies against infectious disease within the body, along with the potential to encode multiple different antibodies in the same organism at the same time. However, the researchers noted, the antibody levels shown in the rabbits in the study likely would not be sufficient to protect against an active infection, and more research is needed to explore how this technology can ultimately be applied to develop effective treatments for humans in the future.
“We are pleased that with this project we were able to show, for the first time, significant systemic levels of functional antibody transcribed from an mRNA upon intramuscular injection,” said Patrick Baumhof, Senior Vice President for Technology at CureVac. “The possibility of simultaneous expression of three distinct antibodies within the same animal shows the potential of mRNA antibody technology.”
In light of recent monkeypox outbreaks around the world, the researchers believe that their technology-based study will contribute to future-generation countermeasures that can prevent and treat diseases caused by pathogenic poxviruses, stated senior author Jay Hooper, of USAMRIID.