Emerging from a rabbit hole – experts analysis needed! Blood and spit tests of IgG responses amongst different vaxx combinations and the unvaxxed

Here is a link to a recently released paper from Germany. I have read it and have cut and pasted what caught my (inexpert) eye. It looks thorough and “a propos” to much that is being discussed around the SubStack community, so I thought I would post it.

It seems to me that different injections and dosages have different impacts on different age cohorts. Other than that, I have nothing else to offer, so you may want to skip to other places for more informed, qualified and expert analysis!

Frontiers | mRNA vaccines against SARS-CoV-2 induce comparably low long-term IgG Fc galactosylation and sialylation levels but increasing long-term IgG4 responses compared to an adenovirus-based vaccine (frontiersin.org)

ORIGINAL RESEARCH article - Front. Immunol., 12 January 2023 Sec. Vaccines and Molecular Therapeutics https://doi.org/10.3389/fimmu.2022.1020844

analysis of serum-derived and salivary anti-S1 IgG (subclass) and IgA Ab responses as well as anti-S serum IgG1 Fc N-glycosylation patterns of SARS-CoV-2 naïve and pre-infected individuals vaccinated with different vaccine combinations over time to compare and characterize the long-term Ab responses up to day 270 post-immunization.

In Germany, 167 participants broken down as under, after December 2020

·        48 naïve individuals received two doses of the BioNTech/Pfizer

·        25 naïve individuals received two doses of the Moderna vaccine

·        14 naïve individuals received two doses of AstraZeneca

·        12 naïve individuals received one dose of Astra Zeneca and subsequently one dose of BioNTech/Pfizer

·        44 naïve individuals received one dose of Astra Zeneca and subsequently one dose of Moderna

·        14 non-hospitalized pre-infected individuals received one or two doses of BioNTech/Pfizer

·        2 further non-hospitalized pre-infected non-vaccinated individuals as positive controls,

·        8 non-vaccinated naïve subjects as negative controls

IgG Abs lacking fucose are known to have an increased affinity to activating FcyRIIIa and are linked to enhanced tumor-fighting potential as well as protection against HIV and malaria infection

IgG1 and IgG3 are the IgG subclasses with the highest potential to activate the immune system, whereas IgG4 has less activating potential and can even inhibit the effector functions of IgG1 and IgG3.

Both SARS-CoV-2 infection and vaccination initially induce the IgG1 and IgG3 subclasses against the S protein

transient afucosylated and more persistent agalactosylated anti-S IgG (1) Abs have been linked to pro-inflammatory disease conditions in COVID-19 patients

severe COVID-19 conditions have also been linked to the appearance of broad autoreactive IgG Abs

Results

All three vaccines induced higher anti-S1 serum IgG levels after the second as compared to the first vaccination indicating a re-activation of memory B cells

Two vaccinations with an mRNA vaccine induced higher anti-S1 serum IgG levels than two vaccinations with the adenovirus-based vaccine

the high mRNA-induced anti-S1 serum IgG levels of naïve and pre-infected individuals waned and approached over time the long-term levels observed following two adenovirus-based vaccinations

mRNA vaccines initially induce anti-S1 IgG1 followed by IgG3 and IgG2 and hardly any IgG4 responses

vaccination with AstraZeneca mainly results in anti-S IgG1 and IgG3, but hardly any IgG2 and IgG4 in the first weeks after immunization of naïve individuals

intense differences in early anti-S1 IgG1 than in early IgG3 levels between the naïve mRNA and adenovirus groups, with the high initial mRNA-induced anti-S1 IgG response dominated by IgG1.

Over time, anti-S1 IgG1 and IgG3 levels became comparable between the different naïve vaccination groups

The anti-S1 serum IgG1-3 levels of naïve and the IgG1 levels of pre-infected vaccinees positively correlated with their total anti-S1 serum.. in contrast, the anti-S1 serum IgG4 levels of naïve individuals vaccinated with mRNA vaccines showed a significant or in tendency negative correlation with their total anti-S1 serum IgG levels

anti-S1 serum IgG4 levels of naïve individuals vaccinated twice with mRNA-1273 significantly correlated with their total anti-S1 serum IgG levels - when only long-term samples (between day 209-256 upon the first immunization) were considered

two immunizations or at least a second immunization with an mRNA vaccine generated detectable long-term IgG4 responses in naïve individuals. (Moderna vaccine showed a higher potential to generate such a late IgG4 response than the BioNTech/Pfizer vaccine.

Over time, the mRNA vaccine-induced IgA levels gradually approached the rather low IgA levels resulting from two AZD1222 vaccinations

The findings suggest a proper, but more decoupled re-activation of local respiratory and systemic S1-reactive IgA+ B cells in pre-infected vaccinees.

The development of the anti-S IgG1 glycosylation from the vacinees were compared to the anti-S IgG1 glycosylation from unvaccinated, hospitalized non-ICU and ICU SARS-CoV-2 patients investigated in the context of our previous study.

(Previous study here: 60. Pongracz T, Nouta J, Wang W, van Meijgaarden KE, Linty F, Vidarsson G, et al. Immunoglobulin G1 fc glycosylation as an early hallmark of severe COVID-19. EBioMedicine (2022) 78:103957. doi: 10.1016/j.ebiom.2022.103957).

This next section proved a step too far for me to understand, no doubt, experts can take a view.

“Anti-S serum IgG1 Fc N-glycosylation

Finally, we analyzed the Fc N-glycosylation patterns of anti-S and total serum IgG1 over time up to day 270 by LC-MS (Figures 4, 5, S5, S6 and Tables S2, S3). The analysis resulted in the identification of 12 IgG1 Fc glycopeptide species (the six major glycan species are schematically shown in Figure 4A), from which glycosylation traits of fucosylation, bisection, sialylation, and galactosylation were calculated.”

Discussion

Neutralizing mucosal Abs play a crucial role in preventing infections of the respiratory tract. Therefore, optimized vaccination strategies against pathogens of the respiratory tract should enhance local antigen-specific long-lived PC and memory B cell responses for generating an improved, long-lasting Ab frontline defense response in the mucosa of the respiratory tract.

Ed- At last, more research (on top of Florida’s decision to “unrecommend” mRNA for under 40 year old men (whilst no-one picked up better outcomes for older women) that suggests different outcomes for different cohorts of people!

Two mRNA immunizations as well as one Astra Zeneca immunization with an mRNA booster, in particular with the Moderna vaccine, induced long-term anti-S1 IgG4 responses.. - .. only mRNA vaccines generate detectable long-term IgG4 responses at least until day 270

In summary, the results suggested distinct adjuvant-specific (inflammatory) potentials of different adjuvants to induce GC-driven antigen-specific IgG Abs with low galactosylation and sialylation levels: CFA (complete Freund’s adjuvant; water-in-oil adjuvant+M.tb.) > IFA, Montanide (both water-in-oil adjuvants) > Alum (aluminum hydroxide) > AddaVax (similar to MF59; squalene-based), Toll-like-receptor ligands (64).

The mRNA and adenovirus-based vaccines induced comparable, relatively low long-term anti-S IgG1 galactosylation levels both in naïve vaccinees and vaccinees with past infection.

These findings suggest that the adenovirus-based and the two mRNA-containing LNP vaccine formats have a comparable, strong potential to influence the quality of the long-term anti-S IgG (1) response

Understanding the long-term adjuvant effects of mRNA and adenovirus-based vaccinations against SARS-CoV-2 will have potential implications on future vaccine designs.

Onwards!

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