Researchers at MIT have developed an enhanced mRNA vaccine system that can elicit a greater immune response at lower doses. The vaccine technology is so potent that it may be useful for intranasal COVID-19 vaccines. This would have the benefit of localized immunity in the nasal mucus membranes that could kill the SARS-CoV-2 virus before it enters the body. The system includes an mRNA strand that encodes the viral spike protein, as with earlier generations of such vaccines, but in this case the strand also encodes for an immune protein called C3d. This protein typically binds to antigens, such as the spike protein, in the body and amplifies the antibody response against them. The mRNA strand included in the vaccine encodes the spike protein already fused with C3d, ensuring a potent immune response.
mRNA vaccines have opened new possibilities in preventing severe disease, which was particularly useful during the recent COVID-19 pandemic. However, these vaccines are still very new, and there is room for improvement. For instance, increasing the immune responses elicited by such vaccines could lead to greater and longer protection from disease, and may also reduce the dose required, which would reduce the cost of treatment and increase access to vaccines in low resource regions. Moreover, a highly potent vaccine may be suitable for intranasal administration.
Not only is this less invasive than injections, and therefore more suitable for children and other nervous patients, but can also lead to strong immunity in the nasal membranes. “With intranasal vaccination, you might be able to kill Covid at the mucus membrane, before it gets into your body,” said Daniel Anderson, a researcher involved in the study. “Intranasal vaccines may also be easier to administer to many people, since they don’t require an injection.”
Traditional mRNA vaccines consist of a lipid nanoparticle enclosing a strand of mRNA that encodes an antigen protein, which in this case is the viral spike protein. The researchers took this one step further, designing the mRNA strand to encode the spike protein fused to C3d, which greatly enhances its stimulatory properties for the immune system, and specifically increases the antibody response. However, the researchers also focused on the lipid composition within the nanoparticle delivery vehicle, as certain lipids can help to enhance immune responses.
“We understood that nanoparticles themselves could be immunostimulatory, but we weren’t quite sure what the chemistry was that was needed to optimize that response,” said Anderson. “So instead of trying to make the perfect one, we made a library and evaluated them, and through that we identified some chemistries that seemed to improve their response.”
Study in journal Nature Biomedical Engineering: Enhancing the immunogenicity of lipid-nanoparticle mRNA vaccines by adjuvanting the ionizable lipid and the mRNA