Toward the Next-Generation COVID-19 Vaccines That Circumvent Antigenic Drift while Defusing Viral Infection

The emergence of vaccine-resistant variants suggests a complicated endemic scenario in the vaccination aftermath for COVID-19. The situation prompts us to enquire whether the antigen adopted by extant vaccines, the trimeric spike (S) protein, is the optimal in the sense of inducing an immunity that leaves the virus with no evolutionary route of evasion. The patterns of glycosylation camouflage suggest that the answer is negative while also suggesting an alternative antigen that appears to be better optimized, eliciting an additional immune attack as the virus gets primed for cell penetration. This type of vaccine is expected to induce antibodies capable of defusing the virus during the priming phase while also circumventing antigenic drift.