Immune senescence, Christian theology, and the Spike protein

One of the things that happens to our immune systems with age is that a preponderance of naïve B-cells (in youth) gives way to a diverse body of memory B-cells (in older adults), each trained to respond to a specific pathogen from the past. (Valter Longo claims that fasting eliminates some of the memory B-cells, which are replaced by naïve B-cells upon re-feeding.)

We know that old and young people have very different responses to COVID and to the COVID vaccines. There is a link between the B-cell story and the differential responses of old and young if we look at a recently re-discovered phenomenon called original antigenic sin. (The term was coined in a 1960 article on influenza.)

(For anyone looking for the Christian theology in this blog, that was it. I apologize for the jokey headline.)

The innate immune system is our first and best line of defense. It is strongest in youth. Neutrophils engulf and digest bacteria and viruses. In addition to neutrophils and natural killer cells, there are short proteins in mucus membranes that protect us.

The mucus layer also contains substances that kill pathogens or inhibit their growth. Among the most abundant of these are antimicrobial peptides, called defensins, which are found in all animals and plants. They are generally short (12–50 amino acids), positively charged, and have hydrophobic or amphipathic domains in their folded structure. They constitute a diverse family with a broad spectrum of antimicrobial activity, including the ability to kill or inactivate Gram-negative and Gram-positive bacteria, fungi (including yeasts), parasites (including protozoa and nematodes), and even enveloped viruses like HIV. Defensins are also the most abundant protein type in neutrophils (see below), which use them to kill phagocytosed pathogens. It is still uncertain how defensins kill pathogens.
Molecular Biology of the Cell, 4th Edition

How do these simple, generic defenses distinguish invaders from self? There are certain molecules that are characteristic of bacteria and absent in eukaryotes.

The pathogen-associated immunostimulants are of various types. Procaryotic translation initiation differs from eucaryotic translation initiation in that formylated methionine, rather than regular methionine, is generally used as the first amino acid. Therefore, any peptide containing formylmethionine at the N-terminus must be of bacterial origin. Formylmethionine-containing peptides act as very potent chemoattractants for neutrophils, which migrate quickly to the source of such peptides and engulf the bacteria that are producing them….Short sequences in bacterial DNA can also act as immunostimulants.
Mol Biol of Cell, 4th Ed

Innate immunity is based on inflammation. I’ve seen several sources that describe how the brilliant, all-purpose system of innate immunity turns to chronic, un-targeted inflammation with age, but no explanation as to how the inflammatory response loses its way and attacks the body generally.

The great resistance that young people have to the COVID virus seems to be due to a strong innate immune system; conversely, the second line of defense, the adaptive immune system, which older people rely on, seems to have more trouble with COVID.

Original antigenic sin (OAS): When the immune system first encounters a pathogen, a tiny subset of randomly-generated antibodies that happens to match a subregion (about 120 AA bases) of some protein in the invader is copied in an exponential process that leads to enormous amplification. Thereafter, the body has a memory of some protein fragments of the pathogen, but not others. When the same pathogen is detected months or years later, the immune system will favor its remembered response, rather than exploring its naïve cells for a new one.

The problem called “original sin” arises when the new invader is a related pathogen, not identical to the one first encountered. The immune system recognizes some subsequences, and figures, based on its memory, “we’ve got this one covered”. But sometimes the response that worked well with the original pathogen is sub-optimal for the new one. The body may fail to fight off a new virus simply because it has encountered a similar one in the past. This is the phenomenon that Thomas Francis dubbed “original sin”.

The relevance to present-day pandemic epidemiology is this: Coronaviruses are ubiquitous, and have been around longer than humans; we have all been exposed to many of them. When our bodies first encounter SARS-CoV-2, they are likely to yawn and say, “this looks a lot like something I’ve seen before”. And indeed, this seems to work well for a lot of bodies. No less a light than John Ioannidis has estimated that up to 80% of people cast off the COVID virus with symptoms so mild that they never know they had it. But there are other people for whom the remembered response to some generic coronavirus is not sufficient, and their immune systems get stuck in an obsolete paradigm. Original sin.

“Original sin” can apply to vaccines as well. The COVID spike protein binds to the ACE2 receptor, and has this in common with spike proteins from many past coronaviruses. This makes it likely that parts of the SARS-CoV-2 spike protein have similar regions to other common coronaviruses from the past, (including the original 2003 SARS). The spike protein, of course, is the element of the virus that was chosen by all Western vaccine manufacturers to induce with their vaccine products. So we see a possible reason why young people and old people have such different reactions to the vaccine: young people are responding to the vaccine from the innate immune systems, while older people are responding by selectively amplifying antibodies from their immune memory.

Age and Vaccine Side Effects

The current crop of mRNA vaccines have caused in 11 months about twice as many adverse reactions, including deaths, as the total of all previous vaccines in the 30-year history of VAERS. These post-vaccination events deserve to be counted and addressed. CDC is in denial.

Reported heart attacks (9,746 cases) and deaths (19,532) after vaccination are skewed toward older people. The average age for heart attacks is 62. [these numbers from OpenVAERS]

Myocarditis and pericarditis (15,403) are skewed toward the young, average age 32, and toward boys more than girls.

When adults do have myocarditis following the jab, it is equally likely to be after the first or second dose. But when young people (<20) get myocarditis, it is most likely to be after the second dose. My interpretation: Adults have been around the block, and they have seen spike proteins before. Their response to the vaccine is from memory B cells. Young people are more likely to be responding from naïve B cells. Something terrible (that I don’t claim to explain) happens when they see the same antigen 3 weeks later.

Neurological damage, including Bell’s Palsy, paralysis, and Guillain-Barre, peak in middle ages (average age 50)

Middle-aged people are also more likely than the young or old to have anaphylactic responses to the vaccines (8,301 total cases). This is surprising, not only in light of the elevated inflammatory response in older people, but also because the old are more likely to have a problem from original sin.



A related phenomenon might be called original vaccination sin. It is peculiar to the newer, cheaper crop of vaccines that are based on a single protein extracted from the virus, rather than on a weakened whole virus, which had been the basis of classic vaccines.

When we develop a vaccine for a pandemic virus based on one small subset of the viral genome, quite predictably, the virus squirm its way out of this artificial barrier by mutating exactly that part of its genome that the vaccine targets. The new variant, with mutations in just the target part of its genome, expands  in just a few months from a rare sub-species to become the dominant infection. Meanwhile, the pharmaceutical manufacturers are geared up to mass-produce a vaccine that no longer targets the current version of the virus. A seasoned Dutch vaccine specialist predicted back in April that just this would happen. As the omicron variant emerges with 37 mutations in the spike protein, scientists who certainly know better feign surprise that so many mutations could arise so quickly, and in just the part of the virus that vaccinated individuals respond to. A high school student’s understanding of natural selection makes it obvious why the COVID virus is mutating in this way.

The good news is that these mutations are likely to make the virus less deadly. The spike protein of SARS-CoV-2 is not an ordinary, evolved spike protein which is evolved to bind well to a receptor and gain entrance to a host cell. This spike protein was engineered in a bioweapons lab to be toxic in multiple ways (in addition, of course, to binding to ACE-2), to break off and enter the bloodstream, spreading its damage far and wide. So when the spike protein mutates to avoid the vaccine, it is likely to become less toxic (while retaining the ability to bind to ACE-2, because that’s what helps the virus to transmit itself.)


ADE = antibody-dependent enhancement (or pathogenic priming) is much better known these days than OAS. ADE or PP refers to any situation in which having been exposed to a virus or bacterium once, the patient becomes sicker on the second exposure. It is much discussed now because of the fear that vaccines could induce ADE, so that some vaccinated people might have worse cases of COVID than if they had not been vaccinated. And indeed there is some evidence for this.

There is no agreement in the community about why ADE happens in some patients some of the time, and there is not even good agreement about how to define ADE. It is possible that the antibody binding to the virus can actually enhance its ability to infect, rather than marking it for destruction.

Some of the definitions of ADE are broad enough to encompass OAS. For example, here is a definition from AAAS. Derek Lowe describes ADE:

Dengue fever is a classic example, because it infects humans through four distinct serotypes. If you are infected with one of these and raise a successful immune response, you may well be at increased risk of serious infection with one of the other serotypes. The neutralizing antibodies for one of the types are often not neutralizing for the others, but instead allow that cell-antibody-receptor mechanism to kick in (easier infection of human monocytes), known as “extrinsic ADE”. There’s also an “intrinsic ADE” seen with dengue, which leads to greater viral replication inside infected monocyte cells before they burst and release their contents. The mechanisms for that are still being worked out, but seem to involve suppression of cytokine pathways.

Here is how Eric Brown describes OAS:

Memory B cells producing antibodies of high affinity and specificity established following a primary exposure to one subset of antigens can prevent or significantly dampen responses by naive B cells to new antigens if they are part of a profile that includes antigens present during the primary exposure (56). This is not a problem if the memory response produces neutralizing antibodies to antigens associated with the secondary exposure; however, problems do arise if memory B cells produce nonneutralizing antibodies to the antigens shared between primary and secondary exposures as reported recently in humans exposed to related human coronaviruses (hCoVs) and later infected with SARS-CoV-2 (78). In such a scenario, not only can the memory response be ineffective, it can significantly attenuate the response of newly activated B cells that could have responded effectively to new antigens absent from the original priming event.


The bottom line
Our immune systems are more complex than we understand. They are brilliantly effective most of the time, but respond to novel stimuli in ways we can’t predict. In general, it seems true that educating the immune system about a pathogen in advance adds protection when that pathogen is encountered later. But there are known and unknown mechanisms by which previous exposure can make a new infection worse.

Vaccine development is an experimental science. The immune system is modified in permanent ways, and there is no theory to tell us whether the benefits or the detriments of an intervention will play out over the years. There is no substitute for long-term trials.

I’ll save the best news for last

The Delta variant had significantly lower mortality than the Wuhan original SARS-CoV-2. Omicron is the up-and-coming strain of COVID, and it has a dramatically lower mortality. There is a simple explanation for this direction of evolution, and I think it’s something we can count on.

In general, viruses evolve to become more contagious and less harmful. It’s in the virus’s interest to co-exist with the host, doing no harm, so it can spread freely. In the case of COVID-19, this evolution has been more rapid and more dramatic than usual. Here’t why:

The spike protein is the part of the virus that is engineered as a bioweapon. The spike protein is responsible for damage to arteries, to nerves, and to the heart that make COVID a fearsome disease. But the spike protein is also the only part of the virus that is induced by the vaccines. Hundreds of millions of people have immunity to the spike protein and nothing else. The virus can continue to spread to the extent that it evades vaccine immunity, and the best way to evade vaccine immunity is via mutations to the spike protein. [recent survey from the SF bay area] These mutations tend to de-fang the spike protein, which was engineered by humans to have multiple toxic effects.

The vaccines are doing their job by guiding the evolution of the virus toward a more benign form. The end game will be that those of us who have not already lived through COVID will be exposed to omicron or something even more benign, and we’ll come through with a lifetime of immunity to all new COVID strains.

28 thoughts on “Immune senescence, Christian theology, and the Spike protein

  1. Hi Josh: Glad to see you back and posting. You were missed.

    You obviously believe that the spike protein was engineered. I have several neighbors who also believe that because of politics, not science.

    Is there some evidence or a paper that would make a connection between the structure of the spike, the ACE2 receptor, and the optimization of the protein structure from wild type, to the Wuhan original SARS-CoV-2. version, that indicates it was weaponized.

    I am grateful for your return,


    • Michael – I wrote about the evidence for a lab origin in two posts back in April, 2020. The quick summary is (1) There is no credible animal source, since pieces of several animal viruses from different locations are included in the genome. (2) No other coronavirus has ever evolved a furin cleavage site. (3) There are published articles (from UNC, WIV, NIAID) describing how to turn a bat coronavirus into a human pathogen. (4) There have been meetings held in the last dozen years in which simulations of a coronavirus pandemic were rehearsed. These meetings were connected to the same people funding the lab experiments in GoF.

  2. Hi Josh, I’m wondering what you think of the recent ban of NAC as a supplement. You have previously posted about it in glowing terms, and it’s something I’ve taken for years – I am honestly both astonished and outraged that it has been restricted in this way, and I would love to hear your take on how this could possibly have happened (certainly, it wasn’t safety concerns!).

    Sorry to “hijack” this post – I have separately posted on-topic 🙂

    • If you read RFK’s new book, it’s clear that our Federal health agencies have been hijacked by profit-making corporations. Any out-of-patent, effective treatments must be pushed aside to make way for the new, profitable medications. So, they’ve discredited vitamin D and zinc and HCQ and IVM precisely because they are cheap and effective. I haven’t seen data on NAC as a COVID treatment, but I don’t think they would be suppressing it if it didn’t work. NAC certainly isn’t dangerous.

  3. Josh:

    I am also glad to see you back and writing. I have been following you on Substack, too.

    I hope your accident recovery is stronger each day.

    You wrote: “The current crop of mRNA vaccines have caused in 11 months about twice as many adverse reactions, including deaths, as the total of all previous vaccines in the 30-year history of VAERS. These post-vaccination events deserve to be counted and addressed. CDC is in denial.”

    Thank you for highlighting that information. It is not easy for the average person to find. The fact that this information is not touted on the news daily is truly egregious, if not criminal.

    All the information in this article is more valuable than rhodium, IMO.

  4. Disclaimer: not a virologist, not an immunologist, not an epidemiologist, not a medical doctor. Only trying to cut through the huge amount on info on this pandemic and build up an opinion.
    I was struck by Josh picking up the “theory” of the Dutch virologist I have followed since the beginning. While I would have really wished to see his narrative debated, which I do not think it really happened publicly, I do not know what to do with it.
    I am not sure if is a conjecture or a theory (as I understand it: selective evolutive pressure increasing variants, vaccine escape, reducing natural immunity, etc …). I assume the author has rather a “theory” in mind as he often writes that what he is saying is textbook knowledge only being discredited by ignorance of his opponents. I do not think he takes his as a conjecture which often is made out of incomplete observations in the need for future research.
    Moreover, I am not sure which independent and rigorous tests are proposed and the level of predictions, both being a gold standard of science progress, IMHO
    Yes, to a certain extent, the “theory” predicted a rise of number of cases in Israel, UK and other countries as high mass vaccination is carried on mid of a pandemic and yes, it predicted something as omicron. However, I did not feel this makes the “theory” standing out as scientific. The same prediction might be made by (i) epidemiologists observing as containment measures might delay heard immunity leaving more time for the virus to mutate which has obviously nothing to do with vaccination and/or (ii) relaxation in the stringency of measures.
    There are other important points of the “theory” related to natural immunity (vs vaccine-induced) supposedly being diminishing by a spike protein vaccine primed immunity. However, I know many are working on this in their labs but do not make such a buzz on social media. I always keep in mind the amplification of one scientist on the net vs 99 working in their labs.

    • Geert vanden Bossche is the Dutch virologist. He is a distinguished virologist at the end of a long career in vaccine development.

      In March, he warned that mass vaccination during a pandemic would drive the virus to mutate. He predicted dire consequences. At the time, I took his prediction seriously, but I didn’t jump on board because I don’t have enough faith that our theory can accurately predict the future.

      Since then, we see that he was absolutely right about mutant versions of the virus, and how quickly they would come to dominate once large segments of the population are vaccinated. However, he was wrong that this would prove to be a bad thing. In fact the mutations have made the virus much less deadly.

      As I said in the article, I believe that this is because this is a man-made virus, and the part of the virus that carries the toxic payload is exactly the part that is delivered in the vaccine. Therefore, when the virus mutates away from our immune response, it also mutates away its toxicity.

      • I hope you will be proven right of course as he does not agree: “Once again, many scientists find themselves with the belief that the emergence of the Omicron variant announces the end of the pandemic and the virus’ transition into endemicity. Their prediction is largely based upon the initial observation that Omicron seems to be causing rather mild disease symptoms which they interpret as being indicative of a virus that—although more infectious—is now becoming less virulent and, therefore, increasingly featuring endemic behavior. I am afraid that once again, I don’t agree—a pandemic can only be tamed by herd immunity.” (web side, dec 7)

    • A differentiation Geert Vanden Bossche makes in reaction to omicron between vaccinated and un-vaccinated which can be put to test. Btw, if true, this also brings back to aging and co-morbidity:
      I still have few other quick questions.
      Why would this “immune reset” with Omicron result in mild/moderate disease initially (due to innate immunity being “reactivated”) when the original Wuhan outbreak started off bad right off the bat… Is this because of some level of pre-existing “herd immunity” and innate immune training to SC2?‍
      Omicron should not be a problem for the unvax’ed whose innate immunity got meanwhile well trained. Older vax’ed age groups have revealed lower case rates (according to PHE) than younger age groups which suggests enhanced affinity of innate Abs (must have been acquired prior to vaccination). Younger vax’ed age groups have high titers of naïve Abs. When set free, those can easily deal with variants (that’s why no youngsters or children got the disease at the beginning of the pandemic). Of course, there are still the people with underlying diseases, most of whom have been jabbed. They cannot rely on their innate Abs and yes, I expect a relatively high case fatality rate in those (unless treated) but of very short duration as a steep incline of infectivity (due to high level of infectiousness) would be followed by a steep decline (due to massive elimination of the virus by a large cohort of +/- simultaneously asymptomatically/ mildly infected individuals.‍

  5. I have previously read the theory of benign evolution of a virus. Yes, it is a good strategy to not commit suicide by rendering your host extinct or nearly so, but I don’t think that happened with smallpox and I have not heard of that happening with HIV. Mutations are random and can go either way. I hope you are right, and Covid will evolve to a more benign state but I’m not holding my breath.

  6. Lawrence:

    Sars Cov 2 and HIV are different viruses.

    Note we do not have a HIV vaccine.

    From Nature Reviews immunology:

    “A major difference between SARS-CoV-2 and HIV-1, however, is that a majority of individuals infected with SARS-CoV-2 clear the virus, while those with HIV-1 do not.

    This is because SARS-CoV-2 is a slowly mutating, non-integrating virus, and the host can rely on a vaccine-primed secondary immune response to clear SARS-CoV-2-infected cells.

    By contrast, HIV-1 integrates into the host genome within ~72 hours of transmission. By the time a vaccine-primed secondary immune response to HIV-1 develops, an irreversible infection has occurred, with a latently infected CD4+ T cell reservoir established with incorporated proviral double-stranded DNA.

    Thus, for a successful HIV-1 vaccine, high levels of protective neutralizing antibodies must be present at the time of transmission to completely prevent infection — which presents a very high bar.”

  7. No one dies of Omicron. Omicron is the Cowpox that protects against Smallpox. If you haven’t already had COVID, run to the nearest person who is sick with the Omicron variant and get as close as you need to assure you are infected.

    Passing through a disease affords robust immunity, because your body learns to respond to many chemical signatures of the pathogen. The best vaccines are based on a weakened virus or bacterium, injected whole into the body. When just a snippet of the virus–a single protein–is injected, the body’s immunity is fragile, and small mutations to that one protein can make your immunity useless or (OAS) worse than useless.

  8. WRT vaccines and spike protein, does someone here have insight into which routine biomarker you normally measure in your blood work might be skewed by the vaccine? Where would you look? A guess would be PTT, S-protein and others related to coagulation and to inflammation of muscle heart, eg high troponin? Thanks.

  9. To me and for the moment this paper (Sept. 2021) put to rest the theory (reportedly also un-falsifiable à-la-Popper) of the escape:
    Holmes EC, Goldstein SA, Rasmussen AL, Robertson DL, Crits-Christoph A, Wertheim JO, Anthony SJ, Barclay WS, Boni MF, Doherty PC, Farrar J, Geoghegan JL, Jiang X, Leibowitz JL, Neil SJD, Skern T, Weiss SR, Worobey M, Andersen KG, Garry RF, Rambaut A. The origins of SARS-CoV-2: A critical review. Cell. 2021 Sep 16;184(19):4848-4856. doi: 10.1016/j.cell.2021.08.017. Epub 2021 Aug 19. PMID: 34480864; PMCID: PMC8373617.
    (the VanityFair’s article should maybe also bring an update ….)

    • Pasqual –
      Perhaps you could summarize for me what argument you found compelling. I found no clarity in the article’s body, but only in its conclusion. 

      The article does not address evidence that COVID was in the US before it was in Wuhan, and it does not consider the organizations that seemed to know with uncanny specificity what kind of pandemic the world would be experiencing. The article does not address the hypothesis that I consider most likely: that SARS-CoV-2 was developed as a bioweapon and deliberately released.

      As for “unfalsifiable”, I would consider the lab-origin hypothesis to be thoroughly refuted if a virus could be isolated from an animal reservoir in nature that had the main features of COVID and could infect humans. I believe it’s true that the SARS-CoV-2 virus is not capable of infecting either bats or pangolins.
      – JJM

      • Josh – sorry but it is not up to me to summarize a paper which I feel speaks for itself. I only wished to balance here argumentations with counter argumentations from a published, peer-reviewed study in a good Journal. You should maybe ask authors for corrections on specifics or full retraction? I must have overlooked the evidence the virus was in US before being in Wuhan, maybe I was not impressed. I would like to find evidence in well done published studies though: on such an important issue I would expect to find some in the ocean which has been published since two years. I also do not think that a paper such as this one needs necessarily to reject all conjectures which have been circulating on the web including the one on bioweapons and intention (maybe that is implicit on the zoonotic origin?). They acknowledge laboratory escape cannot be entirely dismissed though and I might agree the non falsifiability might be argued against (which is why I use the “reportedly”). I still wonder in which sense though. This philosophical stance should be considered in more depth and I would like to read more. Maybe on this stance Occam’s razor argumentation might also be considered, thought they do refer to this implicitly. So, no I put all this to rest, at least for the moment …

  10. @albedo:
    Maybe you could spare the time and take a look at information available here, on this very site? Then one could compare the presented informations, and come to more wellfounded conclusions.

    Where did COVID-19 come from?

    E.g., among many other points:

    The origins of SARS-CoV-2 (your cited study) : ” …nor evidence that the WIV
    possessed or worked on a progenitor of SARS-CoV-2 prior to
    the pandemic.”

    A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence (2015 study by the wuhan laboratory (et al.)):
    ” … we generated and characterized a chimeric virus expressing the spike of bat coronavirus SHC014 …” ; ” … we synthetically re-derived an infectious full-length SHC014 recombinant virus and demonstrate robust viral replication both in vitro and in vivo. ”

    Well, it seems your cited source might be in error.

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