Antibodies work against COVID-19 D614G variant

The body is capable of mounting a humoral immune response with functional cross-reactivity against the D614G variant of SARS-CoV-2, claims a recent Singapore study.

“Overall, our study shows that the D614G mutation on the S protein does not impact SARS-CoV-2 neutralization by the host antibody response, nor confer viral resistance against the humoral immunity,” the researchers said. “Hence, there should be negligible impact towards the efficacy of antibody-based therapies and vaccines that are currently being developed.”

The study included 44 novel coronavirus disease (COVID-19) patients with confirmed D614 infection, and six with G614. Following cell culture experiments, flow cytometry was used to characterize antibody profiles. To measure titres of neutralizing antibodies, pseudotyped lentiviruses were produced and subjected to a neutralization assay. Seven other patients with isolates from other viral clades were also included.

Plasma samples were collected at a median of 31 days postillness onset (pio), during the early recovery phase, and at a postrecovery median of 98 days pio. All patients saw declining immunoglobulin (Ig) M responses over time, such that levels were significantly diminished by 98 vs 31 days pio (p<0.001). [Clin Transl Immunol 2021;10:e1241]

IgG response, on the other hand, was slightly more persistent, though a significant drop in average levels over time was also detected (p<0.05).

Neutralization assays showed that for both the D614 and G614 variants, neutralization capacity, expressed as the log of the half maximal effective concentration (EC₅₀) weakened significantly from 31 to 98 days pio (p<0.001 for both).

Notably, however, the efficacies of neutralizing antibodies were comparable between the two major variants, such that at 31 and 98 days pio, the log EC₅₀ for both the D614 and G614 variants were not statistically different.

“Of clinical importance, all the patients infected with either the D614 or G614 clade elicited a similar degree of neutralization against both D614 and G614 pseudoviruses,” the researchers said, suggesting no impact of the D614G mutation on the neutralization capacity of the antibodies.

In March 2020, a novel variant of SARS-CoV-2 was first detected in Europe, characterized by the nonsynonymous mutation of aspartic acid to glycine at the 614th residue of the virus’ spike protein. By May of the same year, D614G became the dominant variant in Europe, hinting at a potential transmission advantage. [Nat Commun 2020;11:6013]

“Our results support the notion that the locus where the point mutation occurred is not critical for antibody-mediated immunity and may not have an impact on virus resistance towards antibody-based interventions,” the researchers said.

“[I]t is of clinical relevance to assess if cross-reactivity between the variants may enhance viral infection when neutralizing antibodies are present at suboptimal concentrations,” they added. “More importantly, further studies using monoclonal antibodies are necessary to validate the cross-reactivity profiles between both SARS-CoV-2 S variants.”