It’s time for more weapons in the shots-versus-virus arms race.
In the race to build the world’s first round of coronavirus vaccines, the spike protein—the thorny knobs that adorn each of the pathogen’s particles—was our MVP. Spike is a key ingredient in virtually every one of our current pandemic-fighting shots; it has been repeatedly billed as essential for tickling out any immune response worth its salt. “People put all their eggs in the spike basket,” Juliet Morrison, a virologist at UC Riverside, told me. And it undoubtedly paid off. In recent months, though, it’s become clear that the coronavirus is a slippery, shape-shifting foe —and spike appears to be one of its most malleable traits. Eventually, our first generation of spike-centric vaccines will likely become obsolete. To get ahead of that inevitability, several companies are already looking to develop new vaccine formulations packed with additional bits of the coronavirus, ushering in an end to our monogamous affair with spike. The potential perks of this tactic run the gamut: More vaccine ingredients could help the body identify more targets to attack, and loop in untapped reservoirs of immune cells that have no interest in spike. Multifaceted shots also up the ante for the virus, which can alter only so many aspects of its anatomy at once. “It’s like diversifying a portfolio,” William Matchett, a vaccinologist at the University of Minnesota who’s researching reformulated COVID-19 vaccines, told me. To be clear, setting our sights on spike has served us well. The vaccines we’ve built against the coronavirus continue to be astoundingly effective shields against disease largely because the protein is such an excellent teaching tool for an immune system that’s readying itself to duel. Spike, which helps the virus unlock and enter human cells, is one of the pathogen’s most salient and dangerous features, certainly among the first that will be spotted by immune cells and molecules on patrol. Vaccines that teach the immune system to recognize the spike will, in all likelihood, be vaccines that teach the immune system to act effectively, and fast— quickly enough, perhaps, to waylay an invading virus before it even has a chance to break into cells. This process, called neutralization, is carried out by specific types of antibodies, and it holds a venerated status in the field of vaccinology, David Martinez, a vaccine expert at the University of North Carolina at Chapel Hill, told me. Once a vaccinated person produces enough neutralizing antibodies, so the theory goes, they need little else to stave off sickness. And the spike protein appears to be top-notch antibody bait. “Spike is here to stay—it is absolutely necessary,” Smita Iyer, an immunologist at UC Davis, told me. But although antibodies zero in on targets with laser-sharp precision, they are easily discombobulated by change: Even subtle shifts in the spike’s structure can make it harder for molecules to glom on to the surface of the virus and bring it to heel. Antibody-dodging variants of the virus, each carrying slightly rejiggered versions of spike, have now appeared in several countries, including South Africa, Brazil, India, and the United States; more will certainly follow. None of our current vaccines has yet been completely nullified by a coronavirus variant, and vaccine makers such as Moderna and Pfizer are planning to cook up additional shots containing tweaked, variant-conscious versions of spike.
