Chimeric Antibodies and Pemphigoid

After seeing the video mentioned in my post about vaccine induced immunodefiency, I was curious to the reason for the CD4+ cell counts to be decreased.  In the post, I theorized that it was the result of chimeric antibodies.  I posited this because of a quote in the patent that reads:

Chimeric antibodies of interest herein include, but are not limited to, "primatized" antibodies comprising variable domain antigen-binding sequences derived from a non-human primate (e.g., Old World Monkey, Ape etc.) and human constant region sequences.

After looking more into primatized antibodies, I feel that we can add more detail to the original post.
To begin with, a video for anyone wanting an excellent overview of engineered antibodies.  The video is longer than the presenter because of a Q/A session at the end.  It's roughly 30 minutes.


The purpose of using chimeric antibodies is to alleviate the constant stimulation of inflammatory cells in autoimmune conditions, such as Arthritis, by deactivating the cell:

In the pathogenesis of autoimmune diseases, such as rheumatoid arthritis (RA), CD4+ T cells foster and aggravate inflammatory conditions resulting in tissue destruction. One strategy to intervene in these diseases is to short-circuit the inflammatory condition by denying T cells the capacity to be continuously activated and thereby returning the immune system to a state of self-tolerlance.

Elimination of Fc Receptor-Dependent Effector Functions of a Modified IgG4 Monoclonal Antibody to Human CD4

The study above mentions Keliximab and Clenoliximab, which are chimeric anti-CD4 antibodies.  

The chimeric portions on the variable ends of the antibody are from macaque monkeys, and the backbones are IgG1 for Keliximab, and a modified IgG4 for Clenoliximab (more on IgG4 later).



They chose the macaque antibody because of it's exceptional binding affinity to human CD4 antigens.  In contrast, the human MHCII to CD4 binding is so weak that it wasn't measurable until recently. This is by-design; continual activation of CD4+ cells would create autoimmunite problems for us.

Two issues that arise when using anti-CD4 mab's:

Clearance of mab's by host due to elicited immune response: However, the use of murine CD4 mAbs in immunocompetent hosts is limited by the human anti-mouse Ab response that clears the infused mAb and may lead to anaphylactic responses...
A second issue for CD4 mAbs is Ab-mediated depletion of CD4 cells, particularly for chronic therapy, where prolonged depression of CD4 cells may compromise the immune status of patients. For example, severe and prolonged depletion of CD4 cells was observed with the murine-human chimeric mAb (cM-T412) even with a single dose (11).

Elimination of Fc Receptor-Dependent Effector Functions of a Modified IgG4 Monoclonal Antibody to Human CD4

To overcome these issues, reseachers switched from using an IgG1 backbone to using a modified IgG4 backbone. IgG4 backbones have less Fc receptor binding, so they are less likely to activate cells.  The resulting image we get is an anti-CD4 antibody that looks like this:



Although, the use of IgG4 isn't fullproof.  Intermittent cell activation can occur, and the research above mentions "In initial clinical trials, these properties have translated to a reduced incidence of CD4+ T cell depletion."

The crosslinking of CD4 antigens (via 2 antibody sites) with Fc receptor activation enhances the possibility of inducing Fas-mediated cellular death (apoptosis), or other effector functions.  This was one of the development concerns for the use of Clenoliximab; ab-mediated depletion of CD4 cells.  The video above covers this concept around mark 20:25 (enhancing agonism).  



With regard to reduced CD4 counts noticed in some vaccine recipients, the intermittent cell death will serve to decrease CD4 counts, and the mab-Antibody bound CD4 antigens will prevent flow cytometry materials from binding to the cell, thereby also decreasing CD4 counts.  Both will act to induce immunodeficiency.

More on IgG4:
IgG4 antibodies have a somewhat unique property involved in immuno-tolerance, which may be another reason the immunoglobulin was chosen:

Beekeepers, animal laboratory workers and individuals undergoing allergen immunotherapy possess high serum levels of allergen-specific IgG4, which exhibit immunosuppressive functions, protecting the individual from anaphylactic reactions. In autoimmune/immune-mediated diseases, such as pemphigus vulgaris, pemphigus foliaceus and MuSK-myasthenia gravis, IgG4 autoantibodies are pathogenic.

On the role of IgG4 in inflammatory conditions: lessons for IgG4-related disease

IgG4 antibodies are the way the body gets desensitized to venom and bee stings.

The irony behind the quote is that I just recently posted about the emergence of Pemphigoid as a side effect of the vaccine.  This is supporting evidence that IgG4 antibodies are in fact being used.  

This all means that more detail can be added to the graphic in the original post about vaccine induced immunodeficiency, and now it looks like this:



As a side note, the spreadsheet mentioned in the Pemphigoid post can be found here:
drive.protonmail.com...
The spreadsheet lists the peptides referenced in the Moderna patent.  There are sheets for peptides, their function and associated diseases, and now one with the diseases, their descriptions and the peptides associated with causing them.

Why do I read articles like this after midnight, I am tired and can't fathom what I learn when I go to verify the information to see if it is correct when I am tired. Tried doing that many times, and in the morning I don't seem to remember much. Also, I tend to doze off and my head flops back and I get a sore neck...need a higher backed chair I think.

You seem to have done a lot of research on this, I would like to be able to verify if it is interpreted correctly and do an appropriate response.

a reply to: Wisenox

This is big news for someone like me that came down with lot's of side effects and sudden allergic reactions.

Going to read about how I can get such a test here.

a reply to: TDDAgain

If antibodies are the issue for you, this Zeolite study claims that the 8-12 nm size particles can remove IgG antibodies through adsorption.