A group of researchers led by scientists at National Jewish Health, Denver, Colorado, and collaborators from China recently uploaded the results of their study to the preprint server bioRxiv. With a focus on the Lambda variant of interest, the study team recognized the need for a deeper comprehension of the driving mechanisms that make SARS-CoV-2 variants of interest more transmissible than the original wild-type virus from Wuhan, China. This multinational study team sought to break down the elements associated with higher variant infectivity and immune resistance for both the present-day Delta variant and the nascent Lambda. Unfortunately, the authors suspect Lambda could overtake Delta to become the dominant variant.

TrialSite provides a short breakdown of this yet-to-be peer-reviewed and published study.

Are variants becoming more difficult to treat at a high level than the wild-type (original) SARS-CoV-2?

Yes, Delta has demonstrated this. While the original pathogen from China possessed six times more binding affinity directed to the receptor-binding domain (RBD) and angiotensin-converting enzyme 2 (ACE2), the coronavirus entry into the human host cell as compared to the first coronavirus.

The virus can be thought of as almost evolving, although technically it’s not alive or mutating. So as we take the wild-type that first emerged at Wuhan and apply it to the Delta variant, differences emerge and manifest in distinctive mutations and characteristics that propel these mutating pathogens to the top of the dominant order. That’s why they are morphing—to persist and dominate.

Do studies reveal that both Delta from India and Lambda from South America have higher infectious rates?

Yes. This is the case in both the unvaccinated and the vaccinated (breakthrough infections).

What does the study team’s data show when comparing the Pfizer-BioNTech vaccines and the variants of interest?

The study team analyzed sera associated with those who received BNT162b2 (Pfizer-BioNTech) and found that vaccines provided far better protection against the Delta variant versus Lambda. In fact, the study team reports a weaker response to Lambda. 

Does the effectiveness of the Pfizer-BioNTech vaccine wane?

Yes. In this study, it declined in effectivity (a drop in titer of antibodies) by 3-fold just six months post inoculation. This indicates a real problem and hence why booster programs are ultimately discussed openly now. In Israel, which is mostly vaccinated with Pfizer-BioNTech, has been impacted by extensive breakthrough infections. Although it’s one of the most vaccinated countries, they experience now one of the worst pandemic surges.

Did Delta variant boost ACE2 binding as compared to wild-type?

Yes.

How does this play out with monoclonal antibodies?

The authors write that the monoclonal antibody bamlanivimab lowers the binding affinity to Delta variant by about 20-fold and “fully lost binding to Lambda variant.”

What did the team’s structural modeling of complexes of RBD with human receptor (ACE2) and the monoclonal antibody bamlanivimab suggest?

First, they report a “potential basis of the change of binding” but conclude with an even more ominous tone noting that the “Data suggest possible danger and a potential surge of Lambda variant in the near future.”

For a question and answer on Lambda, see the link.

Lead Research/Investigator

Haolin Liu, National Jewish Health, Dept. of Immunology and Genomic Medicine, Denver, CO

Gongyi Zhang, National Jewish Health, Dept. of Immunology and Genomic Medicine, Denver, CO; School of Medicine, Anschutz Medical Center

Other authors can be viewed at the source.

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