An interesting paper came out recently in J. Phys. Chem. Lett.. Based on their analysis of over 2.2 million SARS-CoV-2 genomes, the authors observed -
By tracking the evolutionary trajectories of vaccine-resistant mutations in more than 2.2 million SARS-CoV-2 genomes, we reveal that the occurrence and frequency of vaccine-resistant mutations correlate strongly with the vaccination rates in Europe and America. We anticipate that as a complementary transmission pathway, vaccine-breakthrough or antibody-resistant mutations, like those in Omicron, will become a dominating mechanism of SARS-CoV-2 evolution when most of the world’s population is either vaccinated or infected.
Essentially, the leaky vaccines are allowing vaccine-resistant viral strains to establish themselves by removing their competitors. Conceptually, this is not different from an extensive use of antibiotics leading to the dominance of antibiotic-resistant “superbugs”. When I grew up in India in the 80s, we used to get antibiotics prescribed for every episode of cough, cold and fever. Fast forward to the current era, and you get a scenario like this, where antibiotics stop working.
Leaky Vaccines and Marek-like Scenario
The concept of leaky vaccines causing the transmission of highly virulent pathogens is well known from the BC (Before Covid) era. In the paper “Imperfect Vaccination Can Enhance the Transmission of Highly Virulent Pathogens”, Andrew Read and co-authors wrote -
There is a theoretical expectation that some types of vaccines could prompt the evolution of more virulent (“hotter”) pathogens. This idea follows from the notion that natural selection removes pathogen strains that are so “hot” that they kill their hosts and, therefore, themselves. Vaccines that let the hosts survive but do not prevent the spread of the pathogen relax this selection, allowing the evolution of hotter pathogens to occur. This type of vaccine is often called a leaky vaccine. When vaccines prevent transmission, as is the case for nearly all vaccines used in humans, this type of evolution towards increased virulence is blocked. But when vaccines leak, allowing at least some pathogen transmission, they could create the ecological conditions that would allow hot strains to emerge and persist. This theory proved highly controversial when it was first proposed over a decade ago, but here we report experiments with Marek’s disease virus in poultry that show that modern commercial leaky vaccines can have precisely this effect: they allow the onward transmission of strains otherwise too lethal to persist. Thus, the use of leaky vaccines can facilitate the evolution of pathogen strains that put unvaccinated hosts at greater risk of severe disease. The future challenge is to identify whether there are other types of vaccines used in animals and humans that might also generate these evolutionary risks.
The Marek disease scenario highlighted by the authors turned out to be really catastrophic for the chickens and quite lucrative for the drug companies. Prior to the introduction of the leaky vaccines in the 1970s, Marek disease was harmful but rarely deadly for the chickens. Vaccination led to the spread of highly virulent strains making Marek disease 100% deadly for the unvaccinated chickens.
In case of Covid vaccines, Geert Vanden Bossche warned about the same possibility in March 2021. He also wrote this open letter to WHO around that time proposing a halt to mass vaccination during the pandemic. However, his website and videos got censored by the tech monopolies. You can find Geert’s website here.
Freaky Mutants and Viral Quasiparticle Swarms
Researchers are puzzled by observing multiple substitutions in some of the newly emerging mutants. Here is the description of the highly transmissive Omicron variant from the CDC website -
The spike protein of the Omicron variant is characterized by at least 30 amino acid substitutions, three small deletions, and one small insertion. Notably, 15 of the 30 amino acid substitutions are in the receptor binding domain (RBD). There are also a number of changes and deletions in other genomic regions.
Key Amino Acid Substitutions in Spike Protein (RBD substitutions in bold type): A67V, del69-70, T95I, del142-144, Y145D, del211, L212I, ins214EPE, G339D, S371L, S373P, S375F, K417N, N440K, G446S, S477N, T478K, E484A, Q493R, G496S, Q498R, N501Y, Y505H, T547K, D614G, H655Y, N679K, P681H, N764K, D796Y, N856K, Q954H, N969K, L981F
This is great news for the drug companies, because the existing vaccines will not work for highly mutatated variants and they can sell more of their products. Today the CEO of BioNTech mentioned that the new Omicron vaccine would require three doses on top of all boosters for the existing vaccine. The question of whether that will lead to a human Marek-like scenario remains open.
An even more fundamental question is how the virus is jumping so many evolutionary hoops so easily? A traditional understanding of viral evolution, where a single variant is expected to dominate the space, cannot answer this question. Instead we need to think in terms of quasiparticle swarms (reviewed here, here and here in the BC era).
In this understanding of viral evolution, a virus infecting an organism maintains many variations of its sequence in the infected body among its population. Therefore, it should be described as a viral “cloud” or “quasiparticle swarm” instead of a single variant with a well-defined sequence. This phenomenon has been experimentally observed as reported here and here. From the later paper -
An RNA virus population does not consist of a single genotype; rather, it is an ensemble of related sequences, termed quasispecies. Quasispecies arise from rapid genomic evolution powered by the high mutation rate of RNA viral replication. Although a high mutation rate is dangerous for a virus because it results in nonviable individuals, it has been hypothesized that high mutation rates create a ‘cloud’ of potentially beneficial mutations at the population level, which afford the viral quasispecies a greater probability to evolve and adapt to new environments and challenges during infection. Mathematical models predict that viral quasispecies are not simply a collection of diverse mutants but a group of interactive variants, which together contribute to the characteristics of the population. According to this view, viral populations, rather than individual variants, are the target of evolutionary selection. Here we test this hypothesis by examining the consequences of limiting genomic diversity on viral populations. We find that poliovirus carrying a high-fidelity polymerase replicates at wild-type levels but generates less genomic diversity and is unable to adapt to adverse growth conditions. In infected animals, the reduced viral diversity leads to loss of neurotropism and an attenuated pathogenic phenotype. Notably, using chemical mutagenesis to expand quasispecies diversity of the high-fidelity virus before infection restores neurotropism and pathogenesis. Analysis of viruses isolated from brain provides direct evidence for complementation between members in the quasispecies, indicating that selection indeed occurs at the population level rather than on individual variants. Our study provides direct evidence for a fundamental prediction of the quasispecies theory and establishes a link between mutation rate, population dynamics and pathogenesis.
Dan Sirotkin, who co-authored the first peer-reviewed paper examining the lab-origin of SARS-CoV2 also considered the implications of quasiparticle swarm in the spread of SARS-CoV2 in his excellent blog post here. He argued that immunocompromised people would lead to an emergence of freaky variants out of nowhere. We will cover the implication in a later blog post.