The international team of researchers combined lab-based experiments and epidemiology of vaccine breakthrough infections, showing that the Delta variant is better at replicating and spreading than other commonly-observed variants.
The Delta variant of the SARS-CoV-2 virus, which has become the dominant strain in India and many other countries, most likely spread through its ability to evade neutralising antibodies and increased infectivity, according to a study published in the Nature Journal on Tuesday.
The B.1.617.2 or Delta variant was first observed in India in late 2020.
It has since spread around the globe.
The international team of researchers combined lab-based experiments and epidemiology of vaccine breakthrough infections, showing that the Delta variant is better at replicating and spreading than other commonly-observed variants.
"There's also evidence that neutralising antibodies produced as a result of previous infection or vaccination are less effective at stopping this variant," said Professor Ravindra Gupta from the University of Cambridge in the UK, and one of the study's senior authors.
"These factors are likely to have contributed to the devastating epidemic wave in India during the first quarter of 2021, where as many as half of the cases were individuals who had previously been infected with an earlier variant," Gupta noted.
To examine how well the Delta variant was able to evade the immune response, the team extracted serum from blood samples collected as part of the COVID-19 cohort of the UK's National Institute for Health Research BioResource.
The samples came from individuals who had previously been infected with the coronavirus or who had been vaccinated with either the Oxford/AstraZeneca, known as Covishield in India, or Pfizer vaccines.
Serum contains antibodies raised in response to infection or vaccination.
The team found that the Delta variant virus was 5.7-fold less sensitive to the sera from previously-infected individuals, and as much as eight-fold less sensitive to vaccine sera, compared with the Alpha variant.
In other words, it takes eight times as many antibodies from a vaccinated individual to block the virus.
The researchers also analysed over 100 infected healthcare workers at three Delhi hospitals, nearly all of whom had been vaccinated against SARS-CoV-2.
They found the Delta variant to be transmitted between vaccinated staff to a greater extent than the Alpha variant.
"The Delta variant has spread widely to become the dominant variants worldwide because it is faster to spread and better at infecting individuals than most other variants we have seen," said Partha Rakshit from the National Centre for Disease Control, Delhi, and joint senior author of the study.
"It is also better at getting around existing immunity -- either through previous exposure to the virus or to vaccination -- though the risk of moderate to severe disease is reduced in such cases," Rakshit said.
The spike proteins of the SARS-CoV-2 bind to ACE2, a protein receptor found on the surface of cells in our body. Both the spike protein and ACE2 are then cleaved, allowing genetic material from the virus to enter the host cell.
The virus manipulates the host cell's machinery to allow the virus to replicate and spread.
Using 3D airway organoids -- 'mini-organs' grown from cells from the airway, which mimic its behaviour, the team studied what happens when the virus reaches the respiratory tract.
The researchers used both a live virus and a 'pseudotyped virus', a synthetic form of the virus that mimicked key mutations on the Delta variant and used this to infect the organoids.
They found that the Delta variant was more efficient at breaking into the cells compared with other variants as it carried a larger number of cleaved spikes on its surface.
Once inside the cells, the variant was also better able to replicate.
Both of these factors give the virus a selection advantage compared to other variants, helping explain why it has become so dominant, according to the researchers.
Professor Anurag Agrawal from the CSIR Institute of Genomics and Integrative Biology, Delhi, India, joint senior author of the study, noted that infection of vaccinated healthcare workers with the Delta variant is a significant problem.
"Although they themselves may only experience mild COVID, they risk infecting individuals who have suboptimal immune responses to vaccination due to underlying health conditions and these patients could then be at risk of severe disease," Agrawal said.
"We urgently need to consider ways of boosting vaccine responses against variants among healthcare workers. It also suggests infection control measures will need to continue in the post-vaccine era," he added.
