The first generation of COVID-19 vaccines have been highly effective, but also have limitations: their efficacy can wane without a booster shot, and they may be less effective against some variants. Now, scientists have developed a more targeted vaccine that, in animal studies, shows stronger, broader, and more durable protection in a single, low dose.
Mice, guinea pigs and hamsters were all integral for the development of this breakthrough
The vaccine combines three technologies–immune focusing, self-assembling nanoparticles, and DNA delivery–into a single platform for the first time. In addition to its other advantages, the vaccine could be stored at room temperature, making it potentially easier to transport to remote or developing locations than existing mRNA vaccines, which require specialized cold storage.
“This is among the first next-generation vaccines that will have more advanced features and broader protection,” said Daniel Kulp, Ph.D.,corresponding author of the study.
Existing vaccines include an unmodified receptor binding domain of SARS-CoV-2 spike protein. The new vaccine includes an engineered receptor binding domain that eliminates ‘immune distracting’ sites and can therefore elicit stronger levels of protective, neutralizing antibodies.
Researchers then used proteins that self-assemble to form nanoparticles which display this engineered receptor binding domain. By arranging themselves into structures that resemble an actual virus, the nanoparticles are more easily recognized by the immune system and transported to the germinal centers, where they activate B cells which produce protective antibodies.
Using nucleic acid vaccine delivery technology similar to mRNA, the nanoparticle vaccine is encoded in DNA and delivered into cells thereby giving genetic instructions for the body to build the immunogen internally. This ability to use the body to produce the immunogen within the body is an advance over traditional vaccines methods, which require, for example, the growth of antibodies and pathogens within chicken embryos.
In animal models, researchers found that the DNA delivered immune-focused nanoparticle vaccine produced much higher levels of neutralizing antibodies than the vaccine that wasn’t immune-focused.
“A difficulty with current vaccines is that neutralizing antibodies decline over time,” Kulp said.
The nanoparticle vaccine produced durable responses after a single immunization out to six months in mice, unlike what we are seeing with current SARS-CoV-2 vaccines in people.
The ultimate test for SARS-CoV-2 vaccine candidates is protection from death in SARS-CoV-2 challenge experiments. The researchers found that in a lethal challenge model 100% of mice who received the immune-focused nanoparticle vaccine were protected from death with a single low dose. Most mice that received the standard, non-immune focused vaccine died within 10 days of the challenge.
The vaccine assessment was conducted in both wild-type mice and mice that were genetically engineered to mimic human immune systems, Kulpnoted.
Even without being updated, the immune-focused vaccine showed a comparable level of antibody production to Delta, and other variants, Kulp said. That’s partly because of the immune focusing approach itself, he noted; in blocking parts of the receptive binding domain for the purpose of inhibiting non-neutralizing antibodies, it also blocks many of the areas affected by spike protein mutations. Studies on the Omicron variant are underway.
Researchers are seeking funding to begin human trials of the new nanoparticle vaccine.
~Speaking of Research
*Content taken from press release and modified for content