Although the researchers used only one RBD from one version of Covid, their vaccine produced a robust polyclonal response – meaning it produced multiple types of antibodies, not just one. For Saunders, that’s part of the charm of the approach: Creating many types of antibodies is beneficial, he says, because one that’s extremely effective against one variant might not be as effective against another. Or vice versa: a previously weak antibody could be better at neutralizing a newer variant. “Some of these antibodies will respond great to Omicron, some will respond great to Alpha, some will respond great to Delta,” he says. And some will ideally be great at responding to variants that don’t even exist yet.
Jump start for the vaccine
David Martinez, a postdoctoral researcher at the University of North Carolina at Chapel Hill who was a co-author of several RBD nanoparticle papers, has been investigating whether these types of vaccines can be boosted by an adjuvant: a substance that “boosts” the immune system and is supplied with the vaccine. “If you were asleep in bed, your alarm went off, you didn’t get up, and someone threw an ice-cold bucket of water on you — that’s what an immune system adjuvant can do,” he says.
Adjuvants can be made from lipids, salts, or other types of oils. One variety even contains oil from a shark. They are commonly used in vaccines; For example, the first mRNA Covid vaccines used lipid nanoparticles as an adjuvant.
In the January preprint with Saunders’ lab, the team tested its RBD nanoparticle vaccine with three different types of adjuvants. They found that those with any of the three adjuvants produced higher levels of antibodies compared to the stand-alone vaccine.
A particular adjuvant called 3M-052-AF produced the highest number of antibodies that cross-neutralized different sarbecovirus strains. While the exact formulation is proprietary, the adjuvant contains what is known as a TLR7/8 agonist: small molecules that stimulate immune cells to mount an immune response. These types of molecules can “essentially talk to the immune system and hyperactivate the immune system to counter any external insult it sees,” says Martinez.
Scientists are also researching other nano-based methods for variant-safe vaccination. One of these, dubbed the “nanotrap,” was originally described in matter in June 2021 as a treatment for those already infected and not as a vaccine. A nanotrap is a mechanism to get rid of Covid viruses through phagocytosis, which means a macrophage or other immune cell eats them. Nanotraps act a bit like bait – essentially tricking the body into eating the invading virus.
The idea could work for a variety of viruses, but University of Chicago bioengineer Jun Huang and his team developed one that’s specific to sarbecoviruses because it has a polymeric nanoparticle shell studded with ACE2 receptors, which the There are receptors on human cells that the Covid virus binds to. Due to the high density of ACE2 receptors on the surface of the nanotrap, Covid viruses are attracted to it and get stuck. But this is where the trap comes in: interposed between the ACE2 receptors are ligands, small molecules that can bind to a cell receptor and, in this case, trigger phagocytosis. The body’s macrophages recognize the ligand and eat up the rest of the virus-tainted nanotrap, getting rid of the virus. “We first catch the virus and then eliminate it,” says Huang.