This article is partially rewritten for better readability on October 9, 2021
Aix-Marseille Université in France experimented to determine if antibodies from the COVID-19 vaccines can cause infection enhancement if someone gets infected with the Delta variant.
Antibodies prevent infection. In antibody-dependent enhancement (ADE), the antibodies produced from a previous infection or vaccination facilitate COVID-19 rather than preventing it.
You can read more about ADE here, What is Antibody-Dependent Enhancement, and why should you care?
An experiment done at Aix-Marseille Université in Marseille, France, showed for the first time that antibodies developed against the Wuhan/D614G SARS-CoV-2 make it easier for the Delta variants to enter humans. Viral entry leads to viral multiplication and infection.
The Wuhan SARS-CoV-2 is the original strain that started the COVID-19 pandemic. It has mutated several times since then. Currently, the Delta variants are the overwhelming cause of COVID-19 cases.
Neutralizing and Non-neutralizing Antibodies
Neutralizing antibodies neutralize an antibody by preventing g its entry into a cell. In the case of the spike protein of the SARS-CoV-2, it blocks that part of the spike protein called the Receptor binding domain or RBD to bind to the ACE2 receptor.
The non-neutralizing antibodies can’t neutralize since they attach to sites other than the RBD. They still protect by signaling another cell like a killer T-cell to come to destroy both the antibody-virus complex.
Sometimes, the neutralizing antibody can enhance infection by allowing the virus to enter the macrophages, the front-line cells, for protection. Once they enter, the disease is accelerated.
Lipid Rafts enhance Delta Variant COVID-19
Cells are covered by cell membranes which are made of fat. However, that fat does not have the same consistency throughout. Lipid rafts have a different fat composition, like higher levels of cholesterol which distinguishes them from the other parts of the cell membrane. They are called rafts because they seem to move across the cell membrane.
One function of lipid rafts is to contain proteins that need to work together. In human cells, the ACE2 receptor is in a lipid raft [2]. After the COVID-19 virus attaches to the ACE2, the raft activates other proteins and changes its shape to allow the virus to enter.
In the study, the investigators found that the non-neutralizing antibodies that can enhance infection have a higher affinity for the Delta variants. The non-neutralizing antibody attaches to the other part of the spike protein called the N-terminal domain or NTD.
Once the NTD, non-neutralizing antibody, and lipid raft are joined together, the lipid raft keeps the spike protein in its open conformation. The open shape makes it more stable and adherent to the ACE2 receptor. Once tightly bound to the ACE2, the SARS-CoV-2 virus can multiply or replicate and start an infection.
The viruses produced in the trillions will elicit a hyperimmune response from the host that will attack the viruses and normal human cells. This cytokine storm manifests as Acute Respiratory Distress Syndrome (ARDS) and a multisystem organ failure.
ADE also happens in the dengue virus infection.
Take-Away Message
The changes in the Delta variant make it easier to adhere to the lipid raft and the ACE2 receptor making it more infectious.
COVID-19 in the coming flu season to be diagnosed and treated immediately to prevent an ADE. Neutralizing antibodies induced by the COVID-19 vaccine wanes after six months.
The remaining non-neutralizing antibodies may enhance infection to cause ADE.
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Reference:
- Yahi N, Chahinian H, Fantini J. Infection-enhancing anti-SARS-CoV-2 antibodies recognize both the original Wuhan/D614G strain and Delta variants. A potential risk for mass vaccination? J Infect. 2021 Aug 9:S0163-4453(21)00392-3. doi: 10.1016/j.jinf.2021.08.010. PMID: 34384810; PMCID: PMC8351274.
- Sviridov D, Miller YI, Ballout RA, Remaley AT, Bukrinsky M. Targeting Lipid Rafts-A Potential Therapy for COVID-19. Front Immunol. 2020;11:574508. Published 2020 Sep 29. doi:10.3389/fimmu.2020.574508
Image credit: Lipid raft: By real name: Artur Jan Fijałkowskipl. wiki: WarXcommons: WarXmail: [1]jabber: WarX@jabber.orgirc: [2]consultations: Masur – Own work, Public Domain, https://commons.wikimedia.org/w/index.php?curid=1493810
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