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. The problem is, strategies like these could quickly lock us into a woefully mismatched fencing bout: Microbes mutate much faster than humans invent vaccines, and with every new thrust, we’ll have time only to parry in return. When spike operates alone, it creates an obvious immunological loophole through which a virus might slip.

There’s another solution. We could simply give the immune system more hunks of the virus to target. Several vaccines containing whole coronavirus particles—which have been chemically incapacitated so they can’t cause true infections—have already been authorized, including a couple made by the Chinese company Sinopharm. Whole-virus vaccines, however, can be a pain to produce, and have delivered mixed results in the past.



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