Some COVID-19 Dual-Antibody Therapies Prove Effective Against Variants in Animal Study at WashU

    By Kathleen Berger, Executive Producer for Science and Technology

     COVID-19 therapies made from antibodies are often given to patients who are high risk of severe illness and hospitalization. But virologist and immunologist Michael Diamond, MD, PhD, at Washington University School of Medicine in St. Louis wanted to answer nagging questions about whether such antibody therapies retain their effectiveness against variants of the virus that causes COVID-19.

    “If there was a drug that was available as a (COVID-19) antibody therapy by (for example) AbbVie, AstraZeneca, Eli Lily or Regeneron; what would happen in the context of new variant viruses? We already knew from some studies in cell culture that some of the antibodies might have liabilities against some of the variants, meaning that they might not show as great efficacy, but they had not actually been tested in any animal model to be able to assess whether they could still protect,” explained Diamond.

    The professor of molecular microbiology, and of pathology and immunology wanted to know whether a single antibody therapy or dual antibody combination therapies, available through emergency use authorization or part of advanced clinical trials, would still be effective against new and emerging variants.

    So Diamond’s lab put the therapies to the test against the variants in animal models. In all, the researchers evaluated antibodies corresponding to the FDA-authorized ones made by Eli Lilly and Co., Regeneron and Vir Biotechnology/GlaxoSmithKline, as well as the antibodies that were under development and in clinical trials during study period by AbbVie, Vir and AstraZeneca.

    Many, but not all, dual antibody therapies made from combinations of two antibodies proved effective against a wide range of variants.

    “Most, in particular, the AstraZeneca, Vir, and Regeneron combinations did quite well against all the variants,” said Diamond. “Antibodies that bind different sites may actually work together to get what we call synergy. So if you take one antibody, it has a certain activity, if you take another antibody, it has another activity. If you add the two of them together, you can either get additive activity or you can get even better than that or what we call synergy- such that when the two antibodies are combined, they actually work better than either of the components of the combination.”

    The research suggests that COVID-19 drugs made of two antibodies often retain potency as a therapy against variants and appear to prevent the emergence of drug resistance.

    “Give two antibodies, you have to have almost simultaneous events to get resistance to both components and that turns out to be evolutionarily very challenging for the virus.”

    The initial study took place before the fast spreading Delta variant became a problem. More work needs to be done testing the therapies against the Delta variant in animal models. Diamond said the studies help the FDA make decisions.

    “Our data sort of highlights to the FDA and to others that, hey, you need to evaluate this to make some decisions whether we need to limit the indication for certain antibodies to certain strains or we need to think about broadening the coverage,” said Diamond.