The first generation of Covid-19 vaccines has proven to be remarkably effective. But now that new variants of SARS-CoV-2 are on the rise, the durability and true extent of the protection they offer is being called into question. While we certainly hope that their makers will be able to adapt, there is now evidence that a vaccine capable of immunizing against coronaviruses more broadly—not just SARS-CoV-2 and its new variants—could be on the horizon.
Were this pancoronavirus vaccine to come to fruition, revising existing Covid-19 vaccines year in and year out wouldn’t be necessary.
By William A. Haseltine
Reprinted for educational purposes and social benefit, not for profit.
The first generation of Covid-19 vaccines has proven to be remarkably effective. But now that new variants of SARS-CoV-2 are on the rise, the durability and true extent of the protection they offer is being called into question. While we certainly hope that their makers will be able to adapt, there is now evidence that a vaccine capable of immunizing against coronaviruses more broadly—not just SARS-CoV-2 and its new variants—could be on the horizon. Were this pancoronavirus vaccine to come to fruition, revising existing Covid-19 vaccines year in and year out wouldn’t be necessary.
The first hint that more potent forms of immunization are possible was a preprint study that analyzed, among other things, the immune responses of recovered Covid-19 patients who had also received a dose of either the Moderna or Pfizer-BioNTech mRNA vaccines. Antibody titers from participants who had prior infections and at least one dose of a vaccine were so high, and packed a punch so powerful, they even demonstrated cross-protective capabilities against SARS-CoV-1.
Two new research papers reinforce this concept. Though their methods differ, both use animal models to test whether nanoparticle immunization technology, which combines fragments of different viruses into a single particle and loads it up into a vaccine, is effective at protecting against a large spectrum of coronaviruses. Both also obtained promising results—which, if expanded upon in further studies and eventually clinical trials, could pave the way for a more potent and more broadly protective second generation of vaccines. Not only that, but nanoparticle vaccines are reportedly more cost-effective and easier to develop and store—qualities that will become all the more crucial when the frontlines of immunization campaigns shift to more rural and remote parts of the country.
The first study, conducted by researchers at Duke University and currently undergoing peer view, developed its nanoparticle vaccine using a “cage” made of ferritin, an iron-rich blood protein. The ferritin cage served as a base for constructing a multimeric nanoparticle, aggregating bits of spike protein from different viruses to reach an optimal level of compatibility with the immune system. The average antibody titer elicited by the resulting vaccine was nearly 50,000—a remarkably robust response comparable to that of recovered Covid-19 patients who have also been vaccinated. It also eclipsed the response generated by an mRNA vaccine the researchers made that was functionally similar to those created by Moderna, Pfizer, and BioNTech—the implication being a correlation between high antibody titers and robust immunization.
The second study, which used mice models, was conducted by researchers from Caltech and published in Science this past January. Their nanoparticles were of the “mosaic” variety, consisting of 60 spike protein fragments that were identical in appearance and function, but in actuality taken from up to eight different coronaviruses. Tested against a homotypic nanoparticle—a uniform structure with SARS-CoV-2 fragments only—the mosaic nanoparticles were proven to have more potent binding and neutralizing capabilities. Not only that, but they remained effective against SARS-like coronaviruses found in Chinese, Buglarian, and Kenyan bats, the animal reservoir suspected to be the origins of Covid-19. Even a mosaic that didn’t include a fragment of SARS-CoV-2 was nevertheless able to neutralize the virus, while the mosaic with fragments from eight distinct viruses performed exceptionally well, much better than homotypic SARS-CoV-2. If the first study established the significance of high antibody titers to a strong immune response, this one emphasized that cross-protection can be just as important.
Do nanoparticle vaccines work in animals other than mice? According to the first study, which gave injections to macaque monkeys, the answer is yes. The monkeys received a total of three booster shots and were exposed to not just SARS-CoV-2 and bat coronaviruses, but the B.1.1.7 (UK) variant, SARS-CoV-1, and MERS-CoV as well. While the nanoparticle vaccine performed best against SARS-CoV-2, consistent with the first study its antibodies were cross-protective, effective at neutralizing B.1.1.7, SARS-CoV-1, and bat coronaviruses. Notably, it failed to neutralize seasonal cold-causing coronaviruses and MERS-CoV, a deficiency that can be attributed to differences in their receptor-binding domains. This isn’t a dealbreaker, however, as it can be improved upon in future iterations.
While the longer-term effects of new SARS-CoV-2 variants remain to be seen, by now we should know that any chance we have to outmaneuver this virus and prevent further carnage must be seized with haste. SARS-CoV-2 is unlikely to be the last coronavirus to make the leap from animals to humans, just as Covid-19 won’t be the last lethal pandemic to shift the course of modern life. We must pour resources, funds, and brainpower into further lab and clinical studies that explore our potential to create a pancoronavirus vaccine. If we don’t, the consequences will be far greater than a missed opportunity.