SARS-CoV-2 Vaccine-escape and virulence alleles on the dynamics of pathogen adaptation

More recombination too

As a mere side note, to keep track of my almost 2 years effort to track how utterly useless the vaccines are, I will cursorily mention the paper below.

Similar viral loads in Omicron infections regardless of vaccination status

Similar viral loads and Ct values of BA.1.1 and BA.2 were detected regardless of vaccination history. No correlations between age and BA.1.1 and BA.2 viral load were observed. Conclusion Omicron-infected patients who had received a third vaccine dose had viral loads similar to patients with two doses or who were unvaccinated.

I have been covering the vaccines, and their effects for a long, and the track record on this is massive, but yet again, a new paper shows how utterly useless the vaccines are to stop infection. All the papers I covered about the faults of the vaccine, and especially the Reverse Marek posts, are about to be vindicated. The reason for this post.

Effects of epistasis and recombination between vaccine-escape and virulence alleles on the dynamics of pathogen adaptation

Abstract

Pathogen adaptation to public health interventions such as vaccination may take tortuous routes and involve multiple mutations at different locations in the pathogen genome, acting on distinct phenotypic traits. Yet how these multi-locus adaptations jointly evolve is poorly understood. Here we consider the joint evolution of two adaptations: pathogen escape from the vaccine-induced immune response and adjustments to pathogen virulence affecting transmission or clearance. We elucidate the role played by epistasis and recombination, with an emphasis on the different protective effects of vaccination. We show that vaccines blocking infection, reducing transmission and/or increasing clearance generate positive epistasis between the vaccine-escape and virulence alleles, favouring strains that carry both mutations, whereas vaccines reducing virulence mortality generate negative epistasis, favouring strains that carry either mutation but not both. High rates of recombination can affect these predictions. If epistasis is positive, frequent recombination can prevent the transient build-up of more virulent escape strains. If epistasis is negative, frequent recombination between loci can create an evolutionary bistability, favouring whichever adaptation is more accessible. Our work provides a timely alternative to the variant-centred perspective on pathogen adaptation and captures the effect of different types of vaccine on the interference between multiple adaptive mutations.

The entire abstract is pretty straightforward, how the multi-locus (fancy speak to lots of genetic changes) adaptation comes to be are poorly understood. The decades-old “pathogens only evolve for transmission”, which I never agree with, as anyone who reads me can tell. The go-to propose a “joint evolution” given a different, distinct aspect. Escape from vaccine-induced immunity, and virulence, impacting transmission or clearance. I would say the vaccine immunity will also impact clearance.

Epistasis is the effect a gene has on other genes, in the case of a virus, how certain amino acids can change, given the presence of other changes. A simple, yet insanely complex concept.

Rapid antigenic evolution, allows the pathogen to escape the vaccine-induced immune response. Where did I read that before? Authors go through great lengths to explain and prove their (mathematical btw) model, you should read the entire paper.

Again, a little bit confusing, the paper attempts to make a contrived point in the first image, still pertinent nonetheless. Yet, the current vaccine does only one of these things. It does not increase clearance, also paper forgets to take into account other variables such as waning immunity, and reinfections.

The point in the second image is quite interesting. Recombination defies the assumptions that “fitness” is the paramount evolutionary endpoint of viruses. Mutations that gecko faster growth (replication) will be the ones selected for. Now, tell me again, which mutations lately we have seen in Omicron, and we saw Delta that made it replicate dozens of times faster than other variants

Here we show how different vaccine protections affect the joint evolution of vaccine escape and virulence. When virulence is linked to transmission, vaccines blocking infection, reducing transmission and/or increasing clearance generate positive epistasis and so strains that carry both vaccine-escape and virulence mutations can be favoured transiently and in the long term. In contrast, vaccines reducing virulence mortality generate negative epistasis, favouring one adaptive route or the other, but not both (Table 1). If instead virulence is linked to clearance rate, these predictions change slightly: vaccines blocking infection do not create epistasis, whereas vaccines increasing the clearance rate can create either positive or negative epistasis depending upon the epidemiology (Table 1).

Here are the authorsmentioning something that boggled my mind, without mentioning the current vaccines (don’t block infection, don’t reduce transmission, will aid the virus in not acquiring vaccine-escape, and virulence mutations long term. Just read the first image again. They go on to talk about universal vaccines, and how if not done properly they can lead to more virulent pathogens, but this part popped to my eyes.

Does this description remind you of anything ? I find this paper incredible, and of high value, but some of the author’s points… are rather contrived given the extensive evidence around the current vaccines, and where they are heading. Perhaps other variables would make their equation useful only if run by a quantum computer with a massive data set ?

Reverse Biology is an actual field, but not the way I usually refer to, where the observable effect is the literal opposite of the intended by whatever intervention I am observing, or discussing. Still, some aspects proposed in the paper are valid, and with some adaptation (heh), will be extremely useful from this point forward.

I maintain my position that we are, indeed, in a “reverse Marek” scenario, where the poor non-neutralizing response from vaccinated individuals is selecting the virus to be more immuno evasive, to grow faster, and mildly more virulent.

Our “luck” was Omicron, which threw a massive evolutionary wrench where the virus headed tp. We are truly in uncharted territory, and before someone takes from my post a depressive perspective, no, as of this moment, I do not expect the worst, I just like the science, and learning.

I still highly advise anyone to not take any more Spike-based vaccines. Even if they go to the massive hurdle of developing an Omicron one, which will take a massive effort since a current Omicron vaccine will be useless, which I wrote about it in the post below.

Omicron BA.4, BA. 5 and their consequences

Within the theme of viral evolution, virulence and recombination, I will superficially comment on this paper, since I have been tracking, and was eager to see the effects of monoclonal antibodies in viral evolution, and recombination.

SARS-CoV-2 evolution and immune escape in immunocompromised patients treated with exogenous antibodies

A weak T cell response is what the vaccinated have, most of the time, and especially after a “booster”.