Michaels, Robert A. Comment on “Viral evolution may herald new pandemic phase.” Science Magazine, e-Letter, online: https://science.sciencemag.org/content/371/6525/108/tab-e-letters, 19 January 2021;
Development of vaccines to protect against Covid-19 has progressed to clinical trials against a largely invisible background of rapid genetic evolution of the SARS-CoV-2 RNA virus in the UK and other countries (Kupferschmidt, 8 January). The UK, however, has been a standout for detection of the B.1.1.7 variant and others. Coincidentally, the AstraZeneca/Oxford vaccine collaboration in the UK revealed an anomaly in which effectiveness of its two-dose vaccine regimen was greater when a standard-size booster dose was preceded by a half-size primer dose than when preceded by a full-size primer dose. Clinical trials were conducted over several months. The half-size primer came first, and months later was switched to, and compared with, the full-size primer dose. This timing suggests the hypothesis that the apparent vaccine effectiveness difference, which seems anomalous, predominantly is attributable to genetic changes associated with ascendancy of the UK variant during this interval. This hypothesis, to the degree confirmed, would suggest that diminished effectiveness with the full-size primer dose was attributable to enhanced vaccine resistance of the UK virus variant. It also might suggest, with accelerating vaccination, greater future genetic plasticity of the virus with increasing selective pressure favoring vaccine-escape mutations. This in turn might affect the useful vaccine lifetime, and the frequency of needed vaccine modification to maintain protectiveness against the adapting virus.