Low Neutralizing Antibody Titers against the Mu Variant of SARS-CoV-2 in 31 BNT162b2 Vaccinated Individuals in Colombia

Abstract

Global surveillance programs for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are showing the emergence of variants with mutations in the spike protein. Genomic and laboratory surveillance are important to determine if these variants may be more infectious or less susceptible to antiviral treatments and vaccine-induced antibodies. Three of the most predominant SARS-CoV-2 variants in Colombia during the epidemiological peaks of 2021 were isolated: Mu, a variant of interest; Gamma, a variant of concern; B.1.111, which lacks genetic markers associated with greater virulence. Microneutralization assays were performed by incubating 120 mean tissue culture infectious doses (TCID50) of each SARS-CoV-2 isolate with five two-fold serial dilutions of sera from 31 BNT162b2-vaccinated volunteers. The mean neutralization titer (MN50) was calculated by the Reed-Muench method. At the end of August, Mu represented 49% of coronavirus disease 2019 (COVID-19) cases in Colombia, followed by 25% of Gamma. In contrast, B.1.111 became almost undetectable. The evaluation of neutralizing antibodies suggests that patients vaccinated with BNT162b2 generate neutralizing antibody titers against the Mu variant at significantly lower concentrations relative to B.1.111 and Gamma. This study shows the importance of continuing surveillance programs of emerging variants, as well as the need to evaluate the neutralizing antibody response induced by other vaccines.

Keywords: COVID-19; Mu (B.1.621) variant; SARS-CoV-2 variants; gamma (P.1) variant; neutralizing antibodies; spike protein.

Figure 1

Spatiotemporal distribution of the most representative SARS-CoV-2 lineages in Colombia (bars) and its regions (map). SARS-CoV-2 lineage distribution in the five Colombian regions and Bogotá D.C. December 2020–January 2021 (left), and April–August 2021 (right). Ring colors represent the region. The interactive map is available at https://microreact.org/project/6GjGXeoUW7uVauMTFCFEkE/d9357c6c (accessed on 8 January 2022) [20]. Figure design was based on data by OpenStreetMap (https://openstreetmap.org accessed on 8 January 2022), CC BY-SA 2.0; ODbL. Abbreviations, D.C.: Distrito Capital (Capital District).

Figure 2

Neutralizing titers of BNT162b2-vaccinated volunteers against Mu, Gamma, and B.1.111 SARS-CoV-2 isolates. TCID50-based assays were performed by incubating 120 TCDI50 of each SARS-CoV-2 isolate with five two-fold serial dilutions of sera from BNT162b2-vaccinated volunteers. The MN50 titer was calculated by the Reed–Muench method. Statistical differences between the median values of MN50 titers against Mu, Gamma, and B.1.111 variants were determined using the Kruskal–Wallis test, followed by Dunn’s post hoc test for multiple comparisons. An arbitrary MN50 titer value of 2 was assigned to the 11 out of 31 serum samples that do not neutralize the virus at the lowest dilution (1:4). Abbreviations. n: number of samples, GMT: geometric mean titer, MN50: mean neutralizing antibody titer.