This is because although high-effect mutations that contribute to virus adaption and fitness do occur, they tend to be in the minority compared with tolerated low-effect or no-effect ‘neutral’ amino acid changes 4. Further to understanding epidemiology, sequencing enables identification of emerging SARS-CoV-2 variants and sets of mutations potentially linked to changes in viral properties.Īs highly deleterious mutations are rapidly purged, most mutations observed in genomes sampled from circulating SARS-CoV-2 virions are expected to be either neutral or mildly deleterious. The use of pathogen genomes on this scale to track the spread of the virus internationally, study local outbreaks and inform public health policy signifies a new age in virus genomic investigations 3. Virus genomic sequences are being generated and shared at an unprecedented rate, with more than one million SARS-CoV-2 sequences available via the Global Initiative on Sharing All Influenza Data (GISAID), permitting near real-time surveillance of the unfolding pandemic 2. In this Review, we summarize the literature on mutations of the SARS-CoV-2 spike protein, the primary antigen, focusing on their impacts on antigenicity and contextualizing them in the protein structure, and discuss them in the context of observed mutation frequencies in global sequence datasets.Īs of April 2021, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, accounted for more than 143 million infections and more than three million deaths worldwide 1.
#Spike definition in vitro experiment update#
Nonetheless, manufacturers are preparing platforms for a possible update of vaccine sequences, and it is crucial that surveillance of genetic and antigenic changes in the global virus population is done alongside experiments to elucidate the phenotypic impacts of mutations. There is emerging evidence of reduced neutralization of some SARS-CoV-2 variants by postvaccination serum however, a greater understanding of correlates of protection is required to evaluate how this may impact vaccine effectiveness. Since late 2020, however, SARS-CoV-2 evolution has been characterized by the emergence of sets of mutations, in the context of ‘variants of concern’, that impact virus characteristics, including transmissibility and antigenicity, probably in response to the changing immune profile of the human population. The emergence of SARS-CoV-2 in late 2019 was followed by a period of relative evolutionary stasis lasting about 11 months. Although most mutations in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome are expected to be either deleterious and swiftly purged or relatively neutral, a small proportion will affect functional properties and may alter infectivity, disease severity or interactions with host immunity.
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