SARS-CoV-2 mAb cocktail effective against all known variants of virus
A monoclonal antibody (mAb) cocktail, that targets sites on the Spike protein other than the E484K residue, can neutralise SARS-CoV-2.
A monoclonal antibody (mAb) cocktail to neutralise the COVID-19 virus developed at Vanderbilt University Medical Center (VUMC), US, is effective against all known strains, or variants, of the virus, according to researchers. The study was led by scientists at Washington University School of Medicine in St Louis, US.
In cell culture studies, the researchers determined the ability of mAbs, as well as antibodies isolated from the convalescent plasma of previously infected people, to neutralise highly transmissible variants of the SARS-CoV-2 virus that have arisen in the UK, South Africa, Brazil and elsewhere.
The researchers found that most of the mAbs that have been developed to combat COVID-19 showed “diminished neutralising potency,” specifically against strains of the virus bearing a specific mutation at position 484 in the surface Spike (S) protein, which enables the virus to attach to and enter its host cell in the body.
However, the team also found that several other highly neutralising mAb cocktails, including those developed at VUMC, showed intact or only mildly diminished activity against the variants tested, possibly because they target sites on the S protein other than the highly mutable E484K residue.
The study indicated substantially reduced neutralisation of variants viruses containing this E484K mutation by antibodies in the sera of both previously infected and COVID-19 vaccinated individuals, further highlighting the need for variant-resistant treatments.
“This study highlights the importance of rationally designed antibody cocktails like those we developed,” said Dr James Crowe, director of the Vanderbilt Vaccine Center (VVC). “We chose two antibodies to create a mixture that specifically would resist escape by SARS-CoV-2. Fortunately, this work and several other papers recently published show that the protection mediated by the antibodies we discovered that are now in six different Phase III clinical trials should extend to all current variants of concern.”
Dr Robert Carnahan, associate VVC director said: “These findings that the antibodies we are developing inhibit the new SARS-CoV-2 variants well are made even more important by the fact that some previously approved mAb treatments look very unlikely to protect against these variants. Using our variant-resistant antibody cocktails likely will provide an important new tool for controlling the COVID-19 pandemic.”
The findings were published in Nature Medicine.