Vaccine breakthrough infections with SARS-CoV-2 Alpha mirror mutations in Delta Plus, Iota, and Omicron
Brenda Martínez-González, Lucía Vázquez-Sirvent, María E. Soria, Pablo Mínguez, Llanos Salar-Vidal, Carlos García-Crespo, Isabel Gallego, Ana I. de Ávila, Carlos Llorens, Beatriz Soriano, Ricardo Ramos-Ruiz, Jaime Esteban, Ricardo Fernandez-Roblas, Ignacio Gadea, Carmen Ayuso, Javier Ruíz-Hornillos, Concepción Pérez-Jorge, Esteban Domingo, Celia Perales
Brenda Martínez-González, Lucía Vázquez-Sirvent, María E. Soria, Pablo Mínguez, Llanos Salar-Vidal, Carlos García-Crespo, Isabel Gallego, Ana I. de Ávila, Carlos Llorens, Beatriz Soriano, Ricardo Ramos-Ruiz, Jaime Esteban, Ricardo Fernandez-Roblas, Ignacio Gadea, Carmen Ayuso, Javier Ruíz-Hornillos, Concepción Pérez-Jorge, Esteban Domingo, Celia Perales
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Concise Communication Virology

Vaccine breakthrough infections with SARS-CoV-2 Alpha mirror mutations in Delta Plus, Iota, and Omicron

Abstract

Replication of SARS-CoV-2 in the human population is defined by distributions of mutants that are present at different frequencies within the infected host and can be detected by ultra-deep sequencing techniques. In this study, we examined the SARS-CoV-2 mutant spectra of amplicons from the spike-coding (S-coding) region of 5 nasopharyngeal isolates derived from patients with vaccine breakthrough. Interestingly, all patients became infected with the Alpha variant, but amino acid substitutions that correspond to the Delta Plus, Iota, and Omicron variants were present in the mutant spectra of the resident virus. Deep sequencing analysis of SARS-CoV-2 from patients with vaccine breakthrough revealed a rich reservoir of mutant types and may also identify tolerated substitutions that can be represented in epidemiologically dominant variants.

Authors

Brenda Martínez-González, Lucía Vázquez-Sirvent, María E. Soria, Pablo Mínguez, Llanos Salar-Vidal, Carlos García-Crespo, Isabel Gallego, Ana I. de Ávila, Carlos Llorens, Beatriz Soriano, Ricardo Ramos-Ruiz, Jaime Esteban, Ricardo Fernandez-Roblas, Ignacio Gadea, Carmen Ayuso, Javier Ruíz-Hornillos, Concepción Pérez-Jorge, Esteban Domingo, Celia Perales

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Figure 1

(A) Heatmaps of mutations that define the SARS-CoV-2 variants Alpha, Delta Plus, and Iota as described by the WHO and Omicron as described by Sun et al.

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(A) Heatmaps of mutations that define the SARS-CoV-2 variants Alpha, Del...
(15) (top heatmap) and the corresponding mutations detected in our cohort (n = 5) (bottom heatmap). Amino acid substitutions are displayed in the top row, and their presence in the variants Alpha, Delta Plus, Iota, and Omicron is indicated by a black square. The frequency of the substitutions within the mutant spectrum of each sample (with the patient identification code on the left of each row) is color coded, as shown in the bottom box. Substituted amino acids that map at the same position but that are not identical to the substitutions reported for that position in the Delta Plus, Iota, and Omicron variants are indicated in red in the bottom heatmap (from left to right: F157L, K417R, L452P, and T547A). Mutations and deletions are identified relative to the Wuhan-Hu-1 NCBI reference sequence NC_045512.2. (B) Representation of the six S amplicons used to perform UDS analysis, with indication of the relevant protein domains: signal peptide (SP), N-terminal domain (NTD), the receptor binding domain (RBD), and the S1/S2 cleavage site (S1/S2). Flanking black boxes indicate the amino acids (aa) of the S protein covered by the amplicons. Mutations and deletions that coincide with the Alpha, Delta Plus, Iota, and Omicron variants found in our patient cohort are indicated.