New Polyclonal Antibody XAV-19 Neutralizes the UK and South African Variants

A study published on a preprint server has reported the high neutralizing efficacy of a polyclonal swine antibody against SARS-CoV-2. Polyclonal antibodies which recognize multiple epitopes on the spike protein have been explored as a therapeutic option.

The current study conducted by the company Xenothera produced glycohumanized polyclonal antibodies. The current study examines a glycohumanized swine polyclonal antibody, called XAV-19, that neutralizes the Wuhan D614G strain of the virus, for its ability to show the same activity against the UK and South African (SA) variants as well. The researchers used batches of XAV-219 with neutralizing activity against the viral RBD ranging from a 50% inhibitory concentration (IC50) of 2 to 12 μg/ml.

These were then tested against wildtype spike, as well as spike mutants containing N501Y, N439K, Y453F or E484K. Finally, spike mutants with the combinations of spike alterations found in the UK and SA variants were assayed for neutralization. All single mutations were fully neutralized at IC50, similar to that of the Wuhan type, albeit slightly lower for the E484K mutant. The antibody completely inhibited both UK- and SA-type spike proteins, with the IC50 being 6.4, 4.0 μg/ml, respectively, compared to 4.5 μg/ml for the Wuhan spike. In contrast, banlanivimab, an earlier mAb from Eli Lilly, was also able to inhibit both the Wuhan and the UK variants with a low IC50 of 0.01μg/ml, but could not inhibit the SA spike. Complete neutralization of live virus infection of human Vero cells was also demonstrated with a concentration above 5 μg/ml of XAV-19, but zero activity below 1.5 μg/ml.

The IC50 against Wuhan, UK and SA strains was 2.2 μg/ml for the first two, and 3.2 μg/ml, respectively. Again, bamlanivimab showed a low IC50 of 0.01 μg/ml against the Wuhan and UK lineages but could not neutralize the SA lineage at any concentration. The researchers also carried out two separate experiments to find the TCID100 (tissue culture infective dose 100, which is the concentration required to produce 100% inhibition of the cytopathogenic effect (CPE). For the UK strain, it was 0.78 μg/ml, compared to 1.56 μg/ml with the Wuhan strain. Partial neutralization was observed below 0.78 μg/ml, down to 0.1 μg/ml, for the UK strain, but not for the Wuhan strain. XAV-19 is now under testing in the POLYCOR trial, having already passed phase 2a safety testing at a median serum concentration of 50 μg/ml. The current study shows a high neutralization capacity of all variants at 5 μg/ml.

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