Reasons for Vaccine failure vs Omicron

Antigens go brrrrr

A little bit complicated post, given the fact that you doctors can’t hide vaccine failure against the new Omicron subvariants. I covered Omicron and its differences in this Substack for ages, among a myriad of other mechanisms.

Escape of SARS-CoV-2 variant Omicron to mucosal immunity in vaccinated subjects

Omicron s escape to vaccine-induced systemic antibody responses has been shown in several studies in Omicron-infected patients and vaccine controls.

In the present study we compared mucosal antibody response to Omicron to mucosal antibody response to ancestral strain and Delta variant. This was done on nasal epithelial lining fluid (NELF) prospectively collected in 84 otherwise healthy healthcare workers who had never exhibited PCR-documented COVID-19 and had received three doses of the Pfizer-BioNTech COVID-19 mRNA vaccine.

The authors decided to test why Omicron spread among the vaccinated so far, so broadly, as if there wasn’t any type of resistance from your body while protecting you from severe forms of the disease.

While protection from severe forms of COVID-19 in vaccinated adults is mediated at least in part by SARS-CoV-2-specific antibodies, lessons drawn from other mucosal pathogens suggest that mucosal antibodies and especially secretory immunoglobulin A (sIgA) are those that efficiently block transmission of respiratory viruses such as SARS-CoV-2 9. Therefore, we hypothesize that Omicron disseminates more rapidly than Delta in vaccinated subjects because it escapes vaccine-induced mucosal immune responses.

This is ironic, since they wrote this paragraph themselves, and something no SARS-CoV-2 vaccine effectively did, give you proper mucosal immunity and IgA secretion at sufficient levels. This is part of the reasons all vaccines didn’t work to “stop the spread”.

We found that mucosal IgG and IgA bound less efficiently to the Omicron Spike protein compared to those of Delta or the Wuhan ancestral strain (Figure 1A, 1B). NELF antibodies from vaccinated individuals were also less efficient at inhibiting the binding of the Omicron Spike protein to ACE-2 compared to those of Delta or the ancestral strain (Figure 1C).

The higher the bars, the better!

Our results show that Omicron escapes vaccine-induced mucosal antibody response more efficiently than Delta. This may explain the increased risk of onward transmission of Omicron, consistent with its successful global displacement of Delta in countries with a high vaccination coverage.

Pretty straightforward so far. Omicron escapes mostly the neutralizing immunity from the vaccinated, and even the previously naturally infected, and in this case, it escapes the first and usually most effective barrier of defense and how you begin acquiring immunity against such said viruses. This is part of the explanation. Now to the other part.

First, I have covered this for a long time.

Poor N protein antibody in vaccinated, and vaccines lies

SARS-CoV-2 infects T cells, the power of N protein

A stronger case for Reverse Marek

SARS-CoV-2 - Recombination, Omicron immunity, ADE ?

From the piece above.

Anti-nucleocapsid antibodies following SARS-CoV-2 infection in the blinded phase of the mRNA-1273 Covid-19 vaccine efficacy clinical trial

Results We analyzed data from 1,789 participants (1,298 placebo recipients and 491 vaccine recipients) with SARS-CoV-2 infection during the blinded phase (through March 2021). Among participants with PCR-confirmed Covid-19 illness, seroconversion to anti-N Abs at a median follow up of 53 days post diagnosis occurred in 21/52 (40%) of the mRNA-1273 vaccine recipients vs. 605/648 (93%) of the placebo recipients (p < 0.001). Higher SARS-CoV-2 viral copies at diagnosis was associated with a higher likelihood of anti-N Ab seropositivity (odds ratio 1.90 per 1-log increase; 95% confidence interval 1.59, 2.28).

Following this long-term trend, which anyone who reads the literature and “gets out of its corner” was aware of, here they did the beloved by many of “The Science” crowd blinded trial, to test the efficacy of the Moderna vaccine.

And they found that using their assay (test) the number of people who had proper levels of N antibodies was severely fewer than those naturally infected. 40% vs 94%, and their sample size was not that big, I would expect with massive sample size, that 40% will drop further.

If you want to understand how and why the Nucleocapsid immunity is important from a different mechanistic perspective, you must read the other posts. It is one of the defining reasons why a lot of the vaccinated don’t properly clear the virus, or the viral fragments… more on this in my Long Covid-Gut post soon.

Now to the last, which would belong among this post.

Omicron BA. 4, BA. 5 and the road ahead

Lost inside this piece I talk about a paper on how BA. 1 and BA. 2 were antigenic differently, they have a different immune response, and are similar to “distant cousins”. To further reinforce this.

BA.2 omicron differs immunologically from both BA.1 omicron and pre-omicron variants

Abstract

Background Several studies have shown that SARS-CoV-2 BA.1 omicron is an immune escape variant and current vaccines and infection with pre-omicron variants provide limited protection against BA.1. Meanwhile, however, omicron BA.2 has become the dominant variant in many countries and has replaced BA.1. As BA.2 has several mutations especially in the receptor binding and the N terminal domain compared to BA.1, we analyzed whether BA.2 shows further immune escape relative to BA.1.

Results Unvaccinated individuals after a single exposure to BA.2 had limited cross-neutralizing antibodies to pre-omicron variants and to BA.1. Consequently, our antigenic map, which included all Variants of Concern and both BA.1 and BA.2 omicron sub-variants, showed that both omicron sub-variants are distinct to pre-omicron variants, but that the two omicron variant are also antigenically distinct from each other. The antibody landscapes illustrate that cross-neutralizing antibodies against the whole antigenic space, as described in our maps, are generated only after three or more exposures to antigenically close variants but also after two exposures to antigenically distinct variants.

The results of this paper are rather curious and interesting. In simple terms, the variants are so distinct between them getting an infection with a previous variant won’t give you enough protection to avoid infection with BA. 1 or 2, and being infected with BA. 1 does the same with BA. 2 and vice-versa. By the computer model, they are using cross-protection is achieved after three exposures to close variants or two with distinct variants. An example would be being infected with Delta, and BA. 1 or 2 would give you cross-neutralizing antibodies against other variants.

In my opinion, Omicron should be a strain on itself, SARS-CoV-2.5, or something like that, given how different all of its mechanisms are.

We next analyzed neutralizing antibody titers against the BA.2 omicron variant for a broader selection of samples. We included individuals with single exposure (unvaccinated convalescent from first wave, alpha, beta, delta, BA.1 omicron, or BA.2 omicron variant), with double exposure (unvaccinated after pre-omicron variant and BA.1 omicron re-infection or vaccinated with two doses) or three and more exposures (vaccinated with two or three doses and breakthrough infection). In general, multiple exposures improved neutralizing antibody titers against the BA.2 omicron variant even for individuals that had no contact with the BA.2 omicron variant itself. Relative to the D614G and the delta variants, neutralizing antibody titers against the BA.2 omicron variant were higher in unvaccinated BA.1 or BA.2 omicron variant convalescent persons but lower in most individuals after pre-omicron variant infection or multiple exposure. However, the drop in neutralizing antibody titers against the BA.2 omicron variant in these groups was not as pronounced as we previously showed it against the BA.1 omicron variant. Additionally, most groups, especially after only one or two exposures, had higher titers of neutralizing antibodies against the BA.2 compared to the BA.1 omicron variant.

These data indicate that the BA.2 omicron variant is positioned antigenically between pre-omicron variants and the BA.1 omicron variant but distinct to both.

This entire paragraph goes to describe what I laid out above. BA. 1 and BA. 2 are very distinct among themselves and all the other variants, and exposure to them gives you more neutralizing antibodies to these variants. Individuals exposed to previous variants had very few antibodies against BA. variants.

BA. 2 is positioned between pre-omicron variants and BA. 1, distinct to both, and in my opinion, BA. 2 is a clear sign of some recombination going on among breakthrough infections. Getting the “best of both worlds” as per papers I previously analyzed.

This leads me to link this post from a month ago, where I wrote about a paper demonstrating how Omicron has a poor immune response when used as a vaccine platform. Don’t fall for the same BS twice, since the current generation of vaccines is failing at preventing disease and death, they will most certainly push it.

Omicron BA.4, BA. 5 and their consequences

I hope you all have a nice weekend =) !!!!

Deep appreciation for all the supporters!