  In this article, we propose a theory to explain the reduction in vaccine
effectiveness (VE) against the Delta SARS-CoV-2 variant and decreasing VE over
time reported in recent studies. Using a model illustration, we show that
in-host viral replication dynamics and delays in immune response could play a
key role in VE. Given this, current laboratory approaches solely measuring
reductions in neutralizing ability cannot fully represent the potential impact
of new SARS-CoV-2 variants. We instead propose an alternative approach that
incorporates viral replication dynamics into evaluations of SARS-CoV-2 variant
impact on immunity and VE. This more robust assessment may better inform public
health response to new variants like the newly detected Omicron variant.
