Variant Roulette (Evolution and Immunity Escape)

The Chloroquine Wars Part XLVI

One of the most dreadful propositions of mass vaccination is that large scale vaccination during a pandemic or epidemic promotes the selection of mutations that escape immunity. Generally speaking, most viruses tend to evolve toward greater ability to survive and thrive in a host, but with lessened ability to harm that host. After all, a harmed host is more likely to perish, generally along with all the many living things hitching a ride inside. For these and other reasons, it has been understood by the scientific community that imperfect vaccination can enhance the transmission of viruses (Read et al). This is sometimes referred to as the imperfect vaccine hypothesis or the "leaky" vaccine hypothesis.

As a pandemic wages on, the default expectation is for surviving strains of a virus to be those that find a way to push the boundaries of infectivity in order to keep the infection rate, R, above 1, while lowering the infection fatality rate (IFR) substantially. And while COVID-19 cases and SARS-CoV-2 infections do not necessarily go hand-in-hand, it has certainly been true that CFR has generally declined almost everywhere in the world as the pandemic has moved on, regardless of health care practices.

According to Muller's ratchet, we should expect the ordinary process of evolutionary mutation to also lead to the virus tripping over itself. As random mutations that do not immediately harm the ability of a virus to survive pile up, the probability that further mutation results in an organism that can no longer survive piles up. This further puts weakening evolutionary pressure on a highly virulent asexual organism. This tendency works to our advantage---so long as we don't screw it up.

Sadly, either those running the mass vaccination program don't get it, or they just don't care to be honest about it. Just in time for Independence Day, CNN interviewed a single professor and doctor specializing in infectious diseases who declared that the unvaccinated are "variant factories". The claim quickly went viral, pun intended:

Were this the case, wouldn't it make sense that the "experts" (a plurality of pure illusion manufactured by the multitude of media parrots) would have warned us about this story last year while standing next to both Dr. Anthony Fauci and President "Operation Warp Speed" Donald Trump? Doesn't it seem odd that this story would suddenly make the headlines in July, after seven months of mass vaccination?

It seems more likely that the sudden emergence of this "variant factory" story is a coordinated response to warnings about leaky vaccines put forth by vaccine expert Geert Vander Bossche, echoed in basic principle by evolutionary biologists Bret Weinstein and Heather Heying, along with evidence of dwindling vaccine efficacy. More importantly, it makes no sense. In order to understand why it makes no sense, consider the following contrasting scenarios:

1. In an unvaccinated population, mutations occur at random producing a wide genetic spread with very few progeny resulting in long lasting lineages (Muller's ratchet), with a selection pressure that favors those variants that can (a) win the competition of replication among its cousins within a host, and (b) not kill the host so that it can thrive in new hosts.

2. In a highly vaccinated population, mutations occur at random, but the genetic spread among versions of the virus is narrowed to those that can evade immunity, which has now been made more uniform among the vaccinated population. This further encourages such lineages even when they would not have won out within individual hosts in competition among its cousins. Such evasion increases chances of reinfection.

To be clear: every host is an evolutionary factory for viruses. What should concern us is the nature of streamlining of the process. A picture (even when it represents an oversimplification) is worth a thousand mutations. Variants that can escape immunity are shown in green. The others fail to pass through the sieve that represents the totality of a host's immune system.

The reason public health authorities did not talk about evolutionary escape of variants six or ten or fifteen months ago is that, generally speaking, that conversation does not favor the logic of a mass vaccination program in the middle of a pandemic.

To make this point more clear, let us examine the specifics of the variants that have spread and caused trouble.

• The Alpha variant emerged in the UK in October, which was when Oxford-AstraZeneca was holding vaccine trials there.

• The Beta variant emerged in South Africa, and was first detected in December, 2020, at the tail end of trial periods for both Oxford-AstraZeneca and Pfizer vaccines. This variant carries three mutations in the spike protein.

• The Gamma variant was first detected in Japan, but soon after in Brazil, making the origin a little harder to determine. But since Japan has had far lower viral spread than Brazil, it makes the most sense that Brazil was the source. Both Oxford-AstraZeneca and Pfizer trialed their vaccines in Brazil.

• The Delta variant was first detected in India in October, 2020. India hosted numerous vaccine trials including one for Oxford-AstraZeneca and one for Covishield.

It is noteworthy that variants of interest did not emerge during the early stages of the pandemic, despite mass spread of SARS-CoV-2 around the globe. That's a pretty huge sample size of unvaccinated people. But those that have emerged did so in geographies where vaccine trials were held---that is several variants from a far smaller genetic pool.

Now, let us consider the specific scientific literature examining some of these variants. Virologist Delphine Planas of the Institut Pasteur, along with colleagues, have found that antibodies of vaccinated patients have greatly diminished efficacy in fighting off the Delta strain (emphasis added):

Sera from convalescent patients collected up to 12 months post symptoms were 4 fold less potent against variant Delta, relative to variant Alpha (B.1.1.7). Sera from individuals having received one dose of Pfizer or AstraZeneca vaccines barely inhibited variant Delta. Administration of two doses generated a neutralizing response in 95% of individuals, with titers 3 to 5 fold lower against Delta than Alpha. Thus, variant Delta spread is associated with an escape to antibodies targeting non-RBD and RBD Spike epitopes.

That seems indicative of vaccine-specific escape. In another paper (McCallum et al) the Epsilon variant (B.1.427/B.1.429) showed substantial escape from immunity:

Plasma from individuals vaccinated with a Wuhan-1 isolate-based mRNA vaccine or convalescent individuals exhibited neutralizing titers, which were reduced 2-3.5 fold against the B.1.427/B.1.429 variant relative to wildtype pseudoviruses. The L452R mutation reduced neutralizing activity of 14 out of 34 RBD-specific monoclonal antibodies (mAbs). The S13I and W152C mutations resulted in total loss of neutralization for 10 out of 10 NTD-specific mAbs since the NTD antigenic supersite was remodeled by a shift of the signal peptide cleavage site and formation of a new disulphide bond, as revealed by mass spectrometry and structural studies.

These are most likely not just variants. These appear to be escape variants. These examples both call into question the strategy of targeting the spike protein, but also give us a hint at the potential for disaster. What would happen if one of these variants included an additional mutation that makes COVID-19 explosively more deadly as happened with a leaky vaccine targeting Marek's disease in chickens. The result was an explosively more deadly viral variant that has caused $2 billion in damage to the poultry industry because the escape variants get so hot that they kill every infected bird within just 10 days.

With the delta variant looking far less deadly than previously dominant strains of SARS-CoV-2, we may have gotten lucky. But it's time to reconsider this game of variant roulette.