New Delta sublineage shows no additional resistance to neutralization

By Sam HancockReviewed by Danielle Ellis, B.Sc.Nov 11 2021

Coronavirus disease 2019 (COVID-19) has caused over five million deaths and has spread to nearly every country in the world. When the disease first emerged, many countries were forced to enact costly and restrictive measures to prevent the spread of the disease, including mandatory face masks in public spaces, social distancing, and even stay-at-home orders and lockdowns. While mass vaccination schemes have led many developed countries to open back up, developing countries still struggle.

Study: Neutralisation of SARS-CoV-2 Delta sub-lineage AY.4.2 and B.1.617.2+E484K by BNT162b2 mRNA vaccine-elicited sera. Image Credit: MIA Studio/ Shutterstock

This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources

The rise of dangerous variants of concern has led some to speculate around the re-introduction of restrictions. These variants of concern display several worrying features, including higher transmission rates and the ability to evade both vaccine-induced and natural immunity. The variants tend to show mutations in the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This protein comprises an S1 subunit containing a receptor-binding domain (RBD) that permits viral cell entry and an S2 subunit responsible for membrane fusion. Mutations tend to arise in the RBD, and as the spike protein is the target of most vaccines, this has resulted in significant reductions in the efficacy of the vaccines against some variants.

The AY.2 sublineage of the Delta variant of concern has spread rapidly in recent weeks, rising from 3.8% to 11.3% of new Delta cases in just under a month, and Delta cases already make up 90% of new cases in the UK. Multiple other countries have also reported its presence, with higher lineages seen in some eastern European countries. It appears to have a growth rate of 19% and bears the spike mutation of AY.4 with several additional mutations, known as Y145H and A222V. Researchers are attempting to determine the ability of this new sublineage to avoid neutralization by antibodies elicited from vaccination.

A preprint version of the study is available on the medRxiv* server while the article undergoes peer review.

The study

The researchers assessed the neutralization ability of serum samples that have been vaccinated using the Pfizer/BioNTech mRNA vaccines BNT162b2. A total of 14 samples were evaluated, with donors between the age of 26 and 72. Most were female. Donors submitted samples a minimum of 49 days after the second dose of the vaccine. The presence of anti-SARS-CoV-2 spike protein antibodies was determined using a commercially available ELISA assay.

To test the ability of these samples to neutralize the new sublineage, the samples were tested against clinical isolates from Vero E6 cells. The scientists sequenced the virus beforehand to confirm the presence of the mutations found in AY.4.2 and ensure no new mutations had arisen during cell culture. Statistical analyses consisted of the Friedman test for paired measurements to test for statistically significant differences within paired groups and Dunn’s multiple comparison test, which compares the difference in the sum of ranks.

First, the researchers assessed the ability of the vaccine sera to neutralize AY.4.2 compared to other Delta sublineages, as well as an early pandemic strain. Compared to the early pandemic strain, the AY.4.2 virus showed a 2.3 fold reduction in neutralization ability. This is not unexpected, as most strains that have arisen more recently show significant ability to evade vaccine-induced immunity. Compared to the neutralization titres for the Delta lineage and the parent AY.4 lineage, AY.4.2 showed very little increase in resistance.

The scientists also examined the new lineage compared to a B.1.617.2 (Delta) strain with an E484K mutation in the RBD. This showed a significant reduction in virus neutralization titres compared to both Delta and the AY.4.2 sublineage. The Beta variant also showed more resistance to vaccine sera neutralization than AY.4.2, with a 4.2 fold reduction in virus neutralization compared to an early pandemic strain.

Conclusion

The researchers highlight that the AY.4.2 sublineage does not show a significant reduction in virus neutralization compared to most current strains. This is very likely not the reason for the rapid rise in the percentage of cases. Similar studies support this for the AstraZeneca and Moderna vaccines, which have resulted in very similar results.

The authors show much more concern over the Delta variant that has acquired the E484K spike mutation, as this shows a significantly higher reduction in virus neutralization titres, suggesting it is much more likely to result in vaccine breakthrough infections. While these are mostly far less severe than COVID-19 infections in unvaccinated individuals, they could still be deadly. This information could be important for future vaccine development and public health policymakers, allowing them to make informed decisions on potential measures to reduce the spread of the virus and determine where to target future vaccines against the disease.

This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources