Evidence suggests that mutations occur at a high frequency in the Spike and receptor binding motif (RBM), as a result of recombination events and other positive pressures [
90] and that the RBM is the most divergent region of S [
91] which may lead to the emergence of escape mutants. Variants with several S mutations have been detected in Brazil, Denmark, South Africa, the UK, and USA [
92]. Variants B.1.1.7 and B.1.351 which were first reported in the UK and South Africa, respectively, have caused a great deal of concern regarding their potential impacts on vaccine efficacy. Recent data from in vitro studies demonstrate that vaccinee sera from several different vaccines have significantly decreased neutralization activity against variant B.1.351 compared to older viral isolates while the sera show little or no decreased neutralization against variant B.1.1.7 [
52,
67,
93‐
95]. Phase III trial results from Novavax and AstraZeneca revealed that the vaccines had high efficacy against the B.1.1.7 variant (85.6% and 74.6%, respectively) [
67,
96]. However, efficacy for the Novavax, Johnson & Johnson, and AstraZeneca vaccines were much lower against the B.1.351 variant (49.4%, 57% and <25%, respectively), although the percent efficacy of the AstraZeneca vaccine was only reported for mild and moderate disease [
52,
67,
97]. Based on these data, there is an urgent need to start development of updated versions of leading vaccines in order to protect against the B.1.351 variant, and also to develop a framework for expanded genomic surveillance and rapid analysis of new variants to generate actionable data.
To strengthen surveillance for mutations and variants of concern, CEPI formed a partnership with the GISAID Initiative (
www.gisaid.org), which hosts the largest open access pooled dataset of SARS-CoV-2 genomes (
n = 544,478 full genomes as of 23 February 2021). The GISAID Initiative’s EpiCoVTM application (
www.epicov.org) enables comparative analyses and modeling of sequences and builds a mutation risk map building on knowledge of epitopes and deep mutation scanning experiments [
98].
To rapidly respond to emerging variants, CEPI set up a collaborative project named “Agility” in partnership with Public Health England (PHE), NIBSC, and the GISAID Initiative, to enable the rapid biological assessment of emerging variants both in vitro and in vivo. The Agility project aims to provide open-access high quality reports on the biological implications of emerging variants and inform the need for strain changes or adaptions for vaccines to ensure effectiveness is maintained.