New hope for a Covid-19 vaccine that protects against all variants

The first generation of Covid-19 vaccines has proven to be very effective. But now that new variants of SARS-CoV-2 are on the rise, the durability and true scope of protection they offer is being questioned. While we certainly hope its manufacturers can 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. If this pancoronavirus vaccine were to come to fruition, it would not be necessary to review existing Covid-19 vaccines year after year.

The first hint that more potent forms of immunization are possible was a previous study that looked at, among other things, the immune responses of recovered Covid-19 patients who had also received a dose of Moderna or Pfizer mRNA vaccines. BioNTech. The antibody titers of participants who had previous infections and at least one dose of a vaccine were so high and had such a powerful impact that they even demonstrated cross-protective capabilities against SARS-CoV-1.

Two new research articles reinforce this concept. Although their methods differ, they both use animal models to test whether nanoparticle immunization technology, which combines fragments of different viruses into a single particle and the load in a vaccine, is effective in protecting against a broad spectrum of coronaviruses. Both also had promising results, which, if expanded in additional studies and eventually clinical trials, could pave the way for a stronger and more 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 be even more crucial when the front line of immunization campaigns moves to more rural and remote parts of the world. country.

The first study, conducted by researchers at Duke University and currently undergoing peer review, developed their nanoparticle vaccine using a “cage” made of ferritin, an iron-rich blood protein. The ferritin cage served as the basis for building a multimeric nanoparticle, adding pieces of spike protein from different viruses to achieve an optimal level of compatibility with the immune system. The mean 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 overshadowed 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 mouse models, was conducted by Caltech researchers and published in Sciences last January. Its nanoparticles were of the “mosaic” variety, consisting of 60 spike protein fragments that were identical in appearance and function, but actually taken from up to eight different coronaviruses. Tested against a homotypic nanoparticle, a uniform structure with fragments of SARS-CoV-2 only, mosaic nanoparticles were shown to have more powerful binding and neutralization capabilities. Not only that, but they remained effective against SARS-like coronaviruses found in Chinese, Buglarian and Kenyan bats, the animal reservoir suspected of being the origin of Covid-19. Even a mosaic that did not include a SARS-CoV-2 fragment was able to neutralize the virus, while the mosaic with fragments of eight different viruses performed exceptionally well, much better than homotypic SARS-CoV-2. If the first study established the importance of high antibody titers for a strong immune response, it emphasized that cross-protection may 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 injections and were exposed not only to SARS-CoV-2 and bat coronaviruses, but also to variant B.1.1.7 (UK), SARS-CoV-1 and to MERS-CoV. While the nanoparticle vaccine performed better against SARS-CoV-2, according to the first study, its antibodies were cross-protective, effective in neutralizing B.1.1.7, SARS-CoV-1, and bat coronavirus. In particular, it failed to neutralize the seasonal cold-causing coronaviruses and MERS-CoV, a deficiency that can be attributed to differences in their receptor-binding domains. However, this is not a deal breaker, as it can be improved in future iterations.

While the long-term effects of the new SARS-CoV-2 variants remain to be seen, by now we should know that any chance we have of outpacing this virus and preventing further slaughter must be exploited in haste. SARS-CoV-2 is unlikely to be the latest coronavirus to make the leap from animals to humans, just as Covid-19 will not be the last lethal pandemic to change the course of modern life. We must invest resources, funds and brainpower in more clinical and laboratory studies that explore our potential to create a vaccine against pancoronavirus. If we don’t, the consequences will be far greater than a missed opportunity.