A cluster of the new SARS‐CoV‐2 B.1.621 lineage in Italy and sensitivity of the viral isolate to the BNT162b2 vaccine

Abstract

In this study, we show a seven-individual cluster belonging to the SARS-CoV-2 B.1.621 lineage, imported into Italy by travelers from abroad. We isolated, for the first time, the authentic virus from one of these infected individuals and challenged it against 37 sera of BNT162b2 vaccinated volunteers. Here, we demonstrate that neutralization of SARS-CoV-2 B.1.621 lineage was robust, even if significantly lower than that observed on SARS-CoV-2 B.1. Our findings underline that vigilance of SARS-CoV-2 genomic evolution is fundamental to limit the spread of new SARS-CoV-2 lineages to different countries. Since autumn 2020, SARS-CoV-2 variants have emerged and spread globally. The Centers for Disease Control and Prevention (CDC) classified them as a variant of interest (VOI), variant of concern (VOC), and a variant of high consequence.1 In particular, VOI presents specific genetic markers predicted to affect transmission, diagnostic, therapeutics, or immune escape and are responsible for unique outbreak clusters or increased proportion of cases.2 A new SARS-CoV-2 VOI, defined as B.1.621 lineage, emerged in January 2021 in Colombia. This lineage carries several Spike mutations, some are common with other VOC (E484K, N501Y, P681H) while others are new (R346K, Y144T, Y145S, and 146N insertion).3, 4 To date, the B.1.621 lineage is predominantly retrieved in Colombia, the United States, Spain, the Netherlands, and Denmark.5 To monitor SARS-CoV-2 variants spread in the Brescia area (Northern Italy), a random genomic surveillance program of SARS-CoV-2-positive samples was implemented through Sanger sequencing. On April 20, 2021 during SARS-CoV-2 genomic surveys, we detected a sequence characterized by B.1.621 lineage typical Spike mutations. A whole-genome sequencing (WGS) was performed on this sample, confirming the B.1.621 lineage. Hence, all the contacts of this patient, suffering from unspecific symptoms, were traced allowing the identification of other six SARS-CoV-2-positive patients, whose samples underwent WGS and were assigned to the B.1.621 lineage. These data define the first Italian cluster of the SARS-CoV-2 B.1.621 lineage. The introduction of SARS-CoV-2 B.1.621 lineage in the Brescia area was ascribed to a traveler coming from Colombia. To assess the evolutionary relationships among these seven Italian SARS-CoV-2 B.1.621 lineage sequences on a global scale, a maximum likelihood tree was employed. All our sequences form a monophyletic cluster with the SARS-CoV-2 B.1.621 sequence from the United States (EPI_ISL_1581369) (Figure 1A). Figure 1B shows the key mutations in the SARS-CoV-2 B.1.621 Spike protein. In this study, we isolated for the first time the virus from the sample of the earliest positive patient and carried out a neutralization assay using the isolated virus soon after confirmation of its identity by WGS, and human sera collected between 10 and 20 days after the administration of the second dose of the BNT162b2 vaccine, which occurred 3 weeks after the first immunization. All sera efficiently neutralized the SARS-CoV-2 B.1.621 isolate (Figure 1C), demonstrating that this VOI is not a concern for vaccine efficacy. Indeed, neutralization of SARS-CoV-2 B.1.621 was robust, even if significantly lower than that observed on SARS-CoV-2 B.1. Our data show that despite several mutations in Spike, SARS-CoV-2 B.1.621 is neutralized by the BNT162b2 vaccine-elicited antibodies. Moreover, they highlight the importance of properly quarantining people after travel abroad to avoid spreading newly emerging SARS-CoV-2 lineages to different countries. The authors declare that there are no conflict of interests. Conceptualization: Francesca Caccuri and Arnaldo Caruso. Methodology: Serena Messali, Anna Bertelli, Alberto Zani, and Francesca Caccuri. Investigation: Serena Messali, Anna Bertelli, Alberto Zani, and Francesca Caccuri. Data curation: Serena Messali and Giovanni Campisi. Formal analysis: Serena Messali, Anna Bertelli, and Giovanni Campisi. Supervision: Francesca Caccuri and Arnaldo Caruso. Writing—original draft: Anna Bertelli and Francesca Caccuri. Writing—review and editing: Arnaldo Caruso. Data have been deposited in the Global Initiative on Sharing All Influenza Data (GISAID) database (accession numbers: EPI_ISL_3098720; EPI_ISL_3098721; EPI_ISL_3098722; EPI_ISL_3098723; EPI_ISL_3098724; EPI_ISL_3098725; EPI_ISL_3098726; EPI_ISL_3098727).

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