Characterization of the SARS-CoV-2 B.1.621 (Mu) variant

Abstract

The SARS-CoV-2 B.1.621 (Mu) variant emerged in January 2021 and was categorized as a variant of interest by the World Health Organization in August 2021. This designation prompted us to study the sensitivity of this variant to antibody neutralization. In a live virus neutralization assay with serum samples from individuals vaccinated with the Pfizer/BioNTech or Moderna mRNA vaccines, we measured neutralization antibody titers against B.1.621, an early isolate (spike 614D), and a variant of concern (B.1.351, Beta variant). We observed reduced neutralizing antibody titers against the B.1.621 variant (3.4- to 7-fold reduction, depending on the serum sample and time after the second vaccination) compared to the early isolate and a similar reduction when compared to B.1.351. Likewise, convalescent serum from hamsters previously infected with an early isolate neutralized B.1.621 to a lower degree. Despite this antibody titer reduction, hamsters could not be efficiently rechallenged with the B.1.621 variant, suggesting that the immune response to the first infection is adequate to provide protection against a subsequent infection with the B.1.621 variant.

Fig. 1.

Serum antibody responses to B.1.621 are reduced relative to the parental strain. (A and B) Neutralization antibody titers were measured using human serum samples obtained from individuals vaccinated twice with either the Moderna (A) or Pfizer/BioNTech (B) vaccines. Neutralization assays were performed with an isolate of SARS-CoV-2 with only the D614G mutation in the spike (S-614G) or B.1.621. (C) Neutralization antibody titers were determined using a selected group of human serum samples obtained from individuals vaccinated twice with the Pfizer vaccine (Selected Pfizer). Neutralization assays were performed with an isolate of SARS-CoV-2 with only the D614G mutation in the spike (S-614G), B.1.621, or B.1.351 (beta), a variant of concern. In all groups, each circle or square represents an individual serum sample. The geometric mean of the neutralization titers obtained from a single experiment for each set is indicated by the solid black bars and the numeric values of the geometric means are indicated in parentheses. The lower limit of detection was a dilution of serum at 1:20 and is indicated by the dashed lines.

Fig. 2.

Hamsters previously infected with WA-1 S-614D were partially protected from rechallenge with B.1.621. (A to D) Virus replication in the lungs or nasal turbinates (NT) was measured in groups of naïve hamsters (open bars) or hamsters previously infected with WA-1 S-614D (gray bars). Hamsters were re-challenged with 10³ pfu of S-614D (circles) or B.1.621 (squares) at 8 weeks (A and B) or 28 weeks (C and D) after the first infection. Symbols in the figure indicate individual hamsters in each group from a single experiment (n=3 to 4 per group). Statistical significance was determined in the previously infected hamsters by a Student’s t test between the two challenge viruses (S-614D and B.1.621). Symbols on the x-axis represent virus titers below the limit of detection (10 pfu/g). ****p<0.0001; ns, not significant.

Fig. 3.

SARS-CoV-2 titers are decreased in the lungs of infected hamsters after passive transfer of convalescent human serum. Virus replication of WA-1 S-614G (A) or B.1.621 (B) on day 4 after infection with 10³ pfu of either virus in groups of hamsters treated with convalescent human serum obtained after: 1) vaccination with two doses of the Pfizer vaccine (vaccine serum); 2) infection with SARS-CoV-2 (A.1 lineage), then vaccination with two doses of the Pfizer vaccine (infect-vaccine serum); or 3) administration of pre-pandemic, pooled control serum (control serum). Symbols in the figure indicate individual hamsters (n=3 per group) from a single experiment. Statistical significance was determined by an ordinary one-way analysis of variance (ANOVA) test followed by Tukey’s multiple comparisons, where control serum was the control group. *p <0.01, **p <0.001, ****p <0.0001.