@RolandBakerIII - Roland Baker
@systematic_fun @a_kruschke @newstart_2024 IgG4 class switch was not observed following four doses of Novavax protein-based SARS-CoV-2 vaccine & IgG3 levels were 10x higher them after mRNA vaccines. https://www.journalofinfection.com/article/S0163-4453(24)00053-7/fulltext
@RolandBakerIII - Roland Baker
@systematic_fun @a_kruschke @newstart_2024 IgG3 produced by adenovirus vector vaccines and NVX protein subunit vaccines are 12% of total IgG antibodies but do 80% of the work neutralizing SARS-CoV-2. Natural infection also produce IgG3 predominantly.
@RolandBakerIII - Roland Baker
@systematic_fun @a_kruschke @newstart_2024 But mRNA vaccines class switch to IgG4 antibodies that lack certain FC related functions and are not as good at forming immune complexes. But they are also less inflammatory. If your first two doses were mRNA the class switch has already been fixed.
@RolandBakerIII - Roland Baker
@systematic_fun @a_kruschke @newstart_2024 Since the class switch involves genetic deletion of IgG1, IgG2 and IgG3 there is no way for a memory IgG4 B-cell to ever switch back from IgG4 to IgG3. So the only way to resolve this would be for these memory B-cells to wane entirely which they eventually will.
@RolandBakerIII - Roland Baker
@systematic_fun @a_kruschke @newstart_2024 mRNA vaccines induce memory B-cells but not long lived plasma cells (LLPCs). So they may only last a few years before new B-cells are recruited.
@RolandBakerIII - Roland Baker
@systematic_fun @a_kruschke @newstart_2024 Interestingly if we block IL-4 and IL-13 receptors & tumor necrosis factor this IgG4 class switching doesn't occur during mRNA vaccination. And it doesn't occur using any other vaccine platform. So it is mRNA specific. https://www.medrxiv.org/content/10.1101/2023.09.29.23296354v1
@RolandBakerIII - Roland Baker
@systematic_fun @a_kruschke @newstart_2024 The class switch even occurs if you first have two vector vaccination and then to mRNA vaccinations. https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1309997/full
@RolandBakerIII - Roland Baker
@systematic_fun @a_kruschke @newstart_2024 IgG4 only exists in certain primates and Fab arm exchange only exists in humans due to Arg409 (versus lysine). We simply lack a complete context of why this might be advantageous to humans.
@RolandBakerIII - Roland Baker
@systematic_fun @a_kruschke @newstart_2024 So it is clearly an issue with the mRNA vaccines but we don't know why specifically. Speculation includes elements of the LNP, pseudouridine use or simply elevated expression of spike for much longer than expected and longer than adenovirus. The last option seems plausible.
@a_kruschke - A.Kruschke
@RolandBakerIII @systematic_fun @newstart_2024 Missed the last one. It's intriguing that 2xAZ+2xmRNA show also the IgG4 effect. I would favor the third possibility: PEG-related. AZ contains no LNP, but the polysorbate80.
@APazyryk - Altai Pazyryk
@mrmickme @RolandBakerIII Is there any benefit to IgG3 class switch induced by Novavax?
@notquitegonzo - notquitegonzo עם ישראל חי
@mrmickme @APazyryk @RolandBakerIII Forgive me for my lack of clarity and therefore question Does this indicate a risk for developing auto-immune disorders from nvx booster?
@RolandBakerIII - Roland Baker
@notquitegonzo @mrmickme @APazyryk Antibodies against IL-4, IL-13 receptors& tumor necrosis factor circumvent the class switch to IgG4 with mRNA vaccines. Clearly this is specific to mRNA vax and not ad vector and protein sub-unit vax. https://www.medrxiv.org/content/10.1101/2023.09.29.23296354v1
@RolandBakerIII - Roland Baker
@notquitegonzo @mrmickme @APazyryk No these IgG4 antibodies are specific to the viral spike and don't cause autoimmune disease. The causal connection to IgG4-RD is that you first get an autoimmune disease and the class switch to IgG4 that binds "self" is to prevent damage caused by autoimmune disease.
@a_kruschke - A.Kruschke
@RolandBakerIII @notquitegonzo @mrmickme @APazyryk Could these anti spike IgG4 trigger an immune reaction to the tissues where the spikeproteins are incorporated?
@RolandBakerIII - Roland Baker
@a_kruschke @notquitegonzo @mrmickme @APazyryk Do you mean like where SARS2 spikes are budding from mRNA vaccine or adenovirus vector vaccine transfected cells? Yes, you could see cross reactions to "self" on the cell. But in general IgG4 have less off a tool kit to cause immune reactions than IgG3.
@RolandBakerIII - Roland Baker
@a_kruschke @notquitegonzo @mrmickme @APazyryk If there is an antibody type we should all be worried about it's afucosylated antibodies. They can cause very severe disease.
@a_kruschke - A.Kruschke
@RolandBakerIII @notquitegonzo @mrmickme @APazyryk Yes I meant the reaction to the "Spikeprotein presenting cells". The question was just scientific interest. The other antibodies you mentioned are certainly much more concerning in clinical practice.
@a_kruschke - A.Kruschke
@RolandBakerIII @notquitegonzo @mrmickme @APazyryk Those IgG4 related illnesses are extremely rare. It became a bit less rare meanwhile. M. Ormond/retroperitoneal fibrosis, ... https://pubmed.ncbi.nlm.nih.gov/36814401/ ... mesenterial panniculitis. Pfizer even made a study about. https://www.ehealthme.com/vs/pfizer-biontech-covid-vaccine/mesenteric-panniculitis/