In a pioneering study published in Molecular Therapy, researchers from the University of Oslo have unveiled a revolutionary DNA vaccine that can present influenza to our immune system on a silver (and single-chain variable fragment) platter. Influenza’s second most common external protein is being delivered directly to the immune system cells that need to learn about this invader.
Image by CDC and kstudio on Freepik
Influenza viruses, with their envelope glycoproteins hemagglutinin (HA) and neuraminidase (NA), are notorious for causing annual human flu epidemics. NA is the second most common influenza A envelope protein and is crucial to viral replication and release from infected cells. Targeting NA can prevent the spread of the virus and alleviate flu symptoms.
Vaccine development commonly focuses on stimulating immune responses by presenting antigens derived from the extracellular part of a virus to antigen-presenting cells (APCs) to initiate an immune response.
DNA vaccines offer a dynamic and precise approach to training the immune system against specific threats. Unlike inactivated vaccines, which contain premade fragments of dead viruses or attenuated viruses, DNA vaccines introduce a sequence of DNA that encodes a part of the virus. This leads to a robust immune response from both B- and T-cells, offering enhanced protection against future exposures. Furthermore, DNA vaccines are easy to manufacture and do not rely on the use of actual viral components.
Researchers have enhanced DNA vaccinations by combining several different molecular strategies to prime the body against influenza. The team created DNA plasmids that carried the code to produce the NA antigen and attached it to a molecule called a single-chain variable fragment that targets APCs. After injection, the plasmid was transcribed into mRNA, translated into protein, and the vaccine was released by muscle cells. These APC-targeted vaccine molecules, called a Vaccibody, successfully triggered a robust immune response and provided the mice in this study with complete protection against influenza.
While no DNA vaccines are currently approved for humans in the US, ongoing clinical trials aim to improve their efficacy and safety. The APC-targeted approach developed by Werninghaus et al. holds great promise, increasing the uptake of vaccine proteins by APCs and stimulating a more potent immune response for influenza. The hope is that this strategy would work well for other diseases, including those caused by other viruses as well as those by bacteria and parasites.
Sources: Molecular Therapy, USHHS, WHO, Frontiers in Immunology
