New avian flu mRNA, horrors within our understanding

(spoiler, going to fail)

Within my self-imposed “rule” on avoiding “bad news” on the weekends or just negative “vibes”, we find ourselves here today, which was actually good, and gave me some time to gather my thoughts and read some more research.

As many of my readers will remember, one long-term focus of mine has been the growing “threat” of highly pathogenic influenza, since the current strain gained substantial ground at the same time the world was hyper-focused on Covid. For 2 years avian flu tallied a huge amount of avian bodies, it impacted poultry and egg prices in certain regions of the world, and slowly, but surely (as evolution often does without a human helping hand) it adapted to some mammal species. Human infections are few and far between, with no single trend to pick up, sometimes a kid in the third world, sometimes an adult, and a few old people, the only trend among every single person infected was dealing with many infected animals, or spending a significant amount of hours with them.

While no significant human infection was observed, certain mammals got severely affected, with hundreds of clustered deaths in South America, and a bunch of “random” deaths from other animals such as foxes (big sad, I love foxes). With the fear of a complete jump to humans, and the potential for enormous profit, of course, the usual suspect would push vaccines to solve this issue.

I also want to leave a tidbit of history before delving into the science. Until January 2020, the whole scientific community that researched mRNA as a therapeutic intervention had very few consensuses, but one of them was that mRNA should never be used as an influenza vaccine because of the temporary, antibody-based response. You can find Pfizer and Moderna CEOs both stating something similar at different times in early 2020 (and how SARS-CoV-2 was different.

Avian Flu and the coming Psy Ops

Development of a nucleoside-modified mRNA vaccine against clade 2.3.4.4b H5 highly pathogenic avian influenza virus

Our laboratory and others previously demonstrated that mRNA-lipid nanoparticle (LNP) vaccines encoding influenza virus HA induce potent immune responses in mice, rabbits, and ferrets, and clinical trials confirm their safety and immunogenicity in humans

We recently developed a multivalent mRNA-LNP vaccine that encodes an HA protein from every influenza virus subtype, including clade 1 H524. This multivalent vaccine protects experimentally infected animals against severe disease and death when challenge strains are antigenically mismatched to the vaccine immunogens24; however, the vaccine is not expected to elicit neutralizing antibodies and sterilizing immunity against mismatched influenza virus strains, such as clade 2.3.4.4b H5 viruses. It is therefore important to also develop tailored-made vaccines precisely matched to influenza virus strains with high pandemic potential

The authors of this paper previously attempted something akin to a rudimentary “universal flu vaccine” in a very broad sense (these are solely my words, not theirs) using many HA proteins, but the vaccine did as one would expect. Protects the animals from death and severe disease, but it didn’t elicit many neutralizing antibodies and broad sterilizing responses.

So they focused on just one clade/strain and elicited a proper response. High antibodies, the sole focus in the last 3 years, antibody-based medicine. Unlike SARS-CoV-2, the influenza viruses mutate fast, hella fast as the kids would say, but what do you think it would happen if there is a non-neutralizing, poorly elicited T cell immune response ?

A proper evolutionary highway. This is where I remind people of the many problems of using mRNA vaccines to combat any type of influenza, but especially highly pathogenic influenza.

The persistent threat of Avian Flu

In the article above I went through a paper that demonstrated that H5 clade of highly pathogenic avian flu was a byproduct of recombination between different “strains” with its origins in a failed vaccine from Egypt, the following is an older paper that we could call “foreshadowing” in a certain poetic sense.

Puzzling inefficiency of H5N1 influenza vaccines in Egyptian poultry

In Egypt, efforts to control the highly pathogenic H5N1 avian influenza virus in poultry and in humans have failed despite increased biosecurity, quarantine, and vaccination at poultry farms.

We propose that the induction of a protective immune response to H5N1 is suppressed for an extended period in young chickens.

Vaccine failure, check.
Absurd focus on antibodies and abs level, check.
Focus solely on one of the viral proteins, check.
Let’s check what you need to deal with influenza infections.

Source

If you are a layperson and is lost in the science so far, there are many problems with the current approach to influenza vaccines, they solely focus on the HA proteins, completely ignoring the NA, and recent work demonstrates that for a better, more broad and potent immune response you need to add NA.

The second problem is an overall problem for all, old and new influenza vaccines, but especially pertinent to mRNA, you need a T cell response to both properly deal and clear the viral infection, and to have long-term protection, and cross-reactivity (in simple terms, means getting infected with an older HxNx can protect from a future HxNx), improper viral clearance will both lead to different types of damage and but evolutionary pressure on the virus.

But above all else, with this over-fixation on antibodies, and the misconception of antibody levels equating to protection long-term, we have this.

As an update on the substack above, Moderna’s Flu vaccine still struggles in Phase 3 trials.

In the substack above I covered a remarkable paper where the authors find that inducing broadly reactive influenza antibodies increases the chances of antibodies targeting your own body and can both induce new autoimmune diseases or exacerbate them, it can accelerate any form of inflammatory or autoimmune disease that may find itself subclinically, in vague terms, laying dormant. And influenza infections, especially improperly dealt with are highly correlated with secondary bacterial Streptococcus pneumonia. This should remind you of something (SARS-CoV-2).

Secondary Streptococcus pneumoniae bacterial infections typically occurs after influenza A virus respiratory infection.Such coinfections often lead to invasive pneumococcal disease. The mechanisms involved in this process are not well understood. Here, using an ex vivo human lung bronchial epithelial cell model, we investigated the biological processes of the host and pneumococcus occurring at this niche, during coinfection with multi-species transcriptomics techniques, and in vivo mouse model experimentation. We observed stark differences in global pneumococcal metabolism in different infection states, as well as viral-induced epithelial cell changes in ciliary function, potentially aiding pneumococcal dissemination. Overall, this study identified broad and targeted biological processes involved in this host-pathogen interaction.

I have been warning for months unless the influenza vaccination is done properly and well-timed in both animals and humans, this will backfire monumentally and instead of avoiding disaster, we will be executing a global, accelerated gain of function project on a highly pathogenic influenza strain. To end this on a positive note, and not the first, the second or the last time.

Ketogenic diet activates protective γδ T cell responses against influenza virus infection

Influenza A virus (IAV) infection–associated morbidity and mortality are a key global health care concern, necessitating the identification of new therapies capable of reducing the severity of IAV infections. In this study, we show that the consumption of a low-carbohydrate, high-fat ketogenic diet (KD) protects mice from lethal IAV infection and disease. KD feeding resulted in an expansion of γδ T cells in the lung that improved barrier functions, thereby enhancing antiviral resistance. Expansion of these protective γδ T cells required metabolic adaptation to a ketogenic diet because neither feeding mice a high-fat, high-carbohydrate diet nor providing chemical ketone body substrate that bypasses hepatic ketogenesis protected against infection. Therefore, KD-mediated immune-metabolic integration represents a viable avenue toward preventing or alleviating influenza disease.

A ketogenic diet is the best way to deal with most influenza infections, among its many other effects on the whole human physiology, its modulation of important immune responses is the most significant in our current situation. This 2020 paper is a very good (and prescient) piece on glucose, ketones, and Covid-19, highly recommend it.

Vibes you should have when reading my Substack

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