Delta Variant: Poised to be Totally Resistant to the Current COVID Vaccines

The Delta variant is the predominant strain causing COVID-19 throughout the world. It has shown resistance to the antibodies produced by the BNT162b2 Pfizer vaccine leading to breakthrough infections among the fully vaccinated.

The mutations in the receptor-binding domain (RBD) allows the Delta variant to avoid the neutralizing antibodies.

Recently, researchers from Osaka University investigated if future mutations of the Delta variant will affect the effectiveness of the current vaccines.

The study was done in 3 major steps.

1. They predicted the mutations in the spike protein of the Delta variants.
2. Construction of Delta spike pseudoviruses from the predicted mutations.
3. Antibodies from individuals vaccinated with the Pfizer BNT162b2 and antibodies from COVID-19 recovered individuals were made to react with the pseudoviruses to know if they neutralize or enhance the infectivity of the Delta variant.

Determination of future Delta variant mutations

The authors used a machine learning program called the Alphafold 2 from Caltech. “Alphafold 2 allows users to predict the 3-D structure of arbitrary proteins”.

The Delta spike Pseudovirus construction

1. Plasmid Construction. Genetic material predicted by Alphafold2 that represents the mutations of the Delta variant was put into plasmids.  Plasmids carry genetic material.
2. Transfection. Next, the plasmids were introduced into human cell lines. This process mimics viral infection of the cells.

The last step is the exposure of the transfected cell lines to the antibodies derived from vaccination and natural immunity of previously COVID-19 infected people.

For a better understanding of the results, let’s look at the spike protein of the SARS-Cov-2.

We will focus on the Receptor-Binding Domain (RBD) and the N-Terminal Domain (NTD) and their functions.

See the image below of a SARS-CoV-2 spike protein magnified by electron microscopy in its prefusion or close conformation (explained below).

The NTD is blue on the left, and the RBD is magenta on top.

The RBD is the one that attaches to the ACE2 receptor. Then, viral entry, viral reproduction followed by infection happens.

Neutralizing antibodies to the RBD block its attachment to the ACE2. The formation of neutralizing antibodies are the goal of COVID-19 vaccination.

The spike protein has two conformations. Close or prefusion and open. Most of the time, it is close. Once opened, it is ready to attach to human cells.

The N-terminal domain (NTD) is responsible for the opening of the spike protein. Once in the open conformation, the spike protein is more infectious. Antibodies to the NTD or anti-NTD can enhance infections by keeping the spike protein in an open shape.

Findings

1. Vaccine-induced anti-NTD antibodies caused the Delta variant to become more infectious rather than neutralizing it.
2. Vaccine-induced antibodies to RBD were neutralizing to the Delta variants at high concentrations only. At low doses, the infection enhancement effect of the anti-NTD takes over.
3. When comparing antibodies produced by the vaccine and previous infection towards the Delta variant, the antibodies produced from vaccination enhance disease more than the naturally acquired antibodies.
4. The infection-enhancing antibodies decrease the neutralizing effect of the anti-RBD antibodies. This results in the Delta variants maintaining their infectivity.
5. The antibodies from natural immunity are more effective in neutralizing the Delta variant and did not enhance infection, unlike the vaccine-induced antibodies.

Bottom line

Vaccine-induced immunity are effective at high concentrations. After 6-8 months of 2 doses of the Pfizer vaccine, the neutralizing effect wanes. That is why there is a push for booster shots right now from the CDC.

The mutations in the NTD of the Delta virus make it more infectious. Infection enhancement, immune enhancement, and antibody-dependent enhancement (ADE) can lead to severe COVID-19 illness.

Related: What is Antibody-Dependent Enhancement, and why should you care. and

Antibody-dependent enhancement can happen to Delta Variant COVID-19

As of now, it looks like we have to rely on natural immunity and effective early treatment of COVID-19.

Knowledge about Covid-19 is rapidly evolving. Information may update as new studies are made. Stay current by subscribing. Feel free to share and like.

Don’t Get Sick!

The preprint study, The SARS-CoV-2 Delta variant, is poised to acquire complete resistance to wild-type spike vaccines was published at medrxiv in August 2021. It is not yet peer-reviewed.

Related:

1. Natural Immunity Protected Tanzania and Zambia from COVID-19
2. Antibody-dependent enhancement can happen to Delta Variant COVID-19
3. Bayes Theorem Confirms Meta-analysis of Ivermectin’s Effectivity against COVID-19
4. Harvard: Immunity from mild COVID-19 infection much better than vaccination
5. Know the Signs of Vaccine-Induced Blood Clotting
6. What is Antibody-Dependent Enhancement and why should you care.
7. Molecular mimicry between the spike protein and humans can shut down platelet production
8. Asymptomatic or mild symptomatic COVID-19 elicits effective and long-lasting antibody responses in children and adolescents.
9. Immune escape: The reason the vaxxed get COVID-19
10. Concerning autopsy findings on a patient who had a COVID shot

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