Omicron renders most monoclonal antibody therapy ineffective : Study
New York : Monoclonal antibody therapy, once hailed as 100 per cent effective in stopping Covid-19 in its tracks, has been defeated by the new super mutant Omicron variant of the coronavirus, according to an international study involving researchers from the US, Japan, and Switzerland.Monoclonal antibodies are proteins designed to attach to a specific target, in this case the spike protein of SARS-CoV-2, which the virus uses to enter human cells. Several studies have shown that monoclonal antibody therapy can stop Covid infection’s progression to ICU admissions and death.The cocktail therapy shot to fame after it was used to treat then US President Donald Trump last October. It was also approved by the US Food and Drug Administration in November last year, and even by the Central Drugs Standards Control Organisation (CDSCO) for use in India in May, 2021.A team of researchers analysed the efficacy of monoclonal antibody treatments from major pharma companies.
The findings, posted on preprint server biorxiv, and not peer-reviewed yet, revealed that the therapy developed by pharma giants like Regeneron, Lilly, and Celltrion “completely lost neutralising activity” when faced with Omicron.However, monoclonal antibody treatments by AstraZeneca and Vir Biotechnology were “minimally affected” or in other words, “retained partial activity”.The recent emergence of the highly-transmissible B.1.1.529 Omicron variant is especially concerning because of the number of mutations – more than 30 in the spike protein.”Our results suggest that several, but not all, of the antibody products in clinical use will lose efficacy against the B.1.1.529 Omicron variant and related strains,” wrote corresponding author Michael S. Diamond, from the Washington University’s school of Medicine, in the study.”Our experiments show a marked loss of inhibitory activity by several of the most highly neutralising monoclonal antibodies that are in advanced clinical development or have emergency use approval,” he added.
The researchers evaluated antibodies that correspond to monotherapy or combination therapy that have shown pre- and post-exposure success in clinical trials and patients infected with historical SARS-CoV-2 isolates.The study is in tandem with preliminary studies showing that several clinically used antibodies lose neutralising activity against Omicron’s spike-expressing recombinant lentiviral or vesicular stomatitis virus (VSV)-based pseudoviruses, the researchers said.Moreover, they noted that although monoclonal antibody treatments by AstraZeneca and Vir Biotechnology “in clinical use may retain benefit, validation experiments in vivo are needed to support this conclusion and inform clinical decisions”.The study also noted several limitations such as the experiments focused on the impact of the extensive sequence changes in the B.1.1.529 spike protein on monoclonal antibodies neutralisation in cell culture. Despite observing differences in neutralising activity with certain monoclonal antibodies, it remains to be determined how this finding translates into effects on clinical protection against Omicron.