Association of E484K and L452R spike protein mutations with SARS-CoV-2 infection in vaccinated persons---Maryland, January – May 2021

Abstract

Background. The E484K and L452R amino acid substitutions on the spike protein of SARS-CoV-2 are associated with reduced neutralization by antibodies from acquired immunity. This study examines the respective association of these mutations with infection in persons who had previously received a COVID-19 vaccine. Methods. Genetic sequences from SARS-CoV-2 specimens collected from Maryland residents and reported to Maryland Department of Health were linked to vaccination history. The prevalence of infections in fully vaccinated persons -- defined as being at least two weeks past receiving the final scheduled dose of a COVID-19 vaccine series -- was compared between infections caused by viruses carrying E484K to those not carrying E484K, and between infections caused by viruses carrying L452R to those not carrying L452R, using logistic regression to adjust for confounding. Results. Of 9,048 sequenced SARS-CoV-2 specimens examined, 265 (2.9%) were collected from fully vaccinated persons. In adjusted analysis, the E484K substitution was associated with an increase in the odds of the sequenced specimen being collected from a fully vaccinated person (OR 1.96, 95% CI, 1.36 to 2.83). The L452R mutation was not significantly associated with infections in vaccinated persons (OR 1.07, 95% CI, 0.69 to 1.68). Conclusion. Though more than 97% of SARS-CoV-2 infections were in persons who were not fully vaccinated, the E484K mutation was associated with increased odds of SARS-CoV-2 infection in vaccinated persons. Linking vaccination and sequencing data can help identify and estimate the impact SARS-CoV-2 mutations may have on vaccine effectiveness.

Clinical and genomic signatures of SARS-CoV-2 Delta breakthrough infections in New York

“…In line with data from other laboratories, the pre-Delta breakthrough infections that we studied in early 2021 displayed a variant distribution similar to infections in unvaccinated individuals, 17 , 18 , 19 , 20 though with signs of a starting sieve effect of neutralizing antibody escape mutations, e.g., E484K. 15 , 16 , 17 , 57 The variant pattern in both breakthrough and unvaccinated cases dramatically changed towards the second half of 2021 with a clear dominance of Delta-associated mutations ( Figure 3 ). In the second half of 2021, breakthrough appeared to be primarily shaped by virological factors that increased transmissibility, facilitated by immunological permeability in times of waning vaccine efficacy.…”

COVID-19 Variant Detection with a High-Fidelity CRISPR-Cas12 Enzyme

“…We, therefore, quickly reconfigured our COVID-19 variant DETECTR assay for the identification of Omicron by targeting the E484A mutation, which alone differentiates Omicron from all other current VBM/VOI/VOC. Given that E484-related mutations are present in multiple circulating variants and have a strong effect on reducing antibody neutralization ( 10 , 51 , 52 ), we further updated our panel of CasDx1 gRNAs to detect all relevant mutations (E, K, Q, and A) at amino acid position 484 ( Fig. 4A , B ).…”

The (apparent) antibody paradox in COVID-19

“…Several factors appear to predispose to these breakthrough infections; age, comorbidities, waning immunity and the emergence and dominance of the delta and omicron variants [ 119–121 ]. Breakthrough infections in vaccinated individuals were more common with SARS-CoV-2 strains bearing mutations at the E484 and N501 positions, including the delta (E484K/N501Y) and omicron (E484A/N501Y) variants [ 122 ]. As noted, vaccines using the founder (Wuhan) strain may not induce optimal cross-protective antibodies (and therefore T cell responses) to other variants [ 123 ].…”