Coronavirus Research Tracking - 9 October
Antibodies regular and small, and a possible Neanderthal legacy
In this week’s Research Tracker we look mostly at antibody therapies.
Regeneron’s antibody cocktail
The experimental antibody “cocktail” (two monoclonal antibodies, so more a Gin & tonic than a cocktail) from Regeneron was well publicised this week after it was given to the US president. This is designed to boost the immune system before the patient has produced their own antibodies against the virus. The company is now seeking emergency use permission. At the moment the main details of their therapy come from a small trial report given to prospective investors last week.
Other potent neutralising antibodies are also being discovered. Combinations that have different mechanisms of activity may be particularly effective, according to some research.
A news article in Science discusses some of the benefits and challenges of using such antibodies. These therapies are usually very expensive.
Smaller antibodies may be cheaper and better
Species in the camel family (camels, llamas and alpacas) are known to produce small antibodies, about a tenth of the normal size. Called nanobodies, these are still effective at neutralising microbes. They are easier and cheaper to produce than conventional antibodies.
A paper published in Nature Communications describes the isolation of one such nanobody from an alpaca injected with SARS-CoV-2 proteins. In laboratory assays using cultured cells it was very effective at preventing a SARS-CoV-2 pseudovirus from binding to the ACE2 receptor. With further development it may be used as a therapy or as part of a diagnostic test.
Two antibodies are better than one
Other research has shown that using two or more neutralising antibodies reduces the chances of encountering a virus lineage that is resistant to the treatment.
A recent pre-print mapped all the mutations in the receptor binding domain of the viral spike protein to determine which could affect antibody binding. This helps with design “escape-resistant” antibody cocktails.
Little cross-reactivity of pre-pandemic antibodies to SARS-CoV-2
A study published in Science looked at antibodies from 232 Covid-19 patients and mapped all the sites on the virus that could be targets for them. They determined there were over 800 potential sites where antibodies could interact with the virus, but only 10 where neutralising antibodies could bind. Stronger and broader antibody responses were found for hospitalised Covid-19 patients compared to those with milder symptoms.
The same study also looked at antibodies collected from 190 samples before the pandemic. These only targeted one SARS-CoV-2 uncharacterised protein, whereas Covid-19-specific antibodies targeted the spike protein and nucleoprotein. This suggests that the pre-pandemic antibodies will not provide effective immune protection.
An opinion in Signal Transduction and Targeted Therapy also points out that previous research reporting human coronavirus-specific T-cells that react to SARS-CoV-2 is not evidence of protective immunity.
Finding other molecules that bind to the virus
A new method for rapid screening of antibody-like particles that bind strongly to the spike protein was published in Science Advances. These may be useful in diagnostic tests to detect the virus. Further research is needed to determine if they are effective therapies as well.
An overview of the virus and its consequences
A detailed review of the characteristics of the virus and the symptoms it causes has been published in Nature Reviews Microbiology. It also notes that there is as yet no conclusion about when and where the virus first infected humans.
“Neanderthal DNA” and Covid-19 risks
Research has indicated that a specific variant (haplotype) of a region covering six genes on chromosome 3 is associated with a higher probability of being hospitalised if the person has Covid-19. A paper published recently in Nature reports that this 50 kb region is also found in Neanderthal genomes.
This could reflect a period, about 50,000 years ago, when populations of Neanderthals and anatomically modern humans in Eurasia interbred. The authors estimated that about 50% of people in South Asia and 16% of people in Europe have the haplotype for increased Covid-19 risk. It is unknown what factors in this genomic region influence the risk of severe Covid-19.
It is incorrect to call this “Neanderthal genes”, as some media have. It is a genetic variant reflecting gene flows, rather than being about genes that are only found in Neanderthals.