Does Geert Vanden Bossche actually know what he’s talking about, or does he just have a bit too much phantasy? Earlier this year, he claimed that a more virulent coronavirus would emerge in highly COVID-19 (C-19) vaccinated countries by the end of June, but - once again - he has misjudged that timeline. Can we still take that man seriously? Or is this just a miscalculation of at most a few weeks, and will his predictions still come true this summer?
If his predictions still hold true, why does it take so long for mutations leading to increased viral virulence to be naturally selected?
We may have overlooked a crucial aspect of viral transmission, namely the post-exposure replication and spread of the virus within the upper respiratory tract (URT)! In C-19 vaccinees, viral replication and spread within the URT is negatively impacted by the adsorption of more infectious progeny virus on the surface of dendritic cells (DCs) patrolling the URT (see Fig. 1 below). Virus adsorption onto DCs reduces the number of infectious viral particles available to infect new target epithelial cells within the URT. The ratio of infectious virus particles to the number of target cells present in a defined space (e.g., the URT) is called the ‘multiplicity of infection’ (MOI). As explained below, understanding MOI helps in interpreting the replication dynamics of infectious agents.
A low MOI is thought to promote natural selection of more infectious variants. However, the cytokine environment created by more infectious SARS-CoV-2 (SC-2) variants causes more progeny virus to adsorb onto the surface of URT-patrolling DCs. Hence, the higher intrinsic infectiousness of newly emerging variants will not lead to a proportional increase in the number of newly produced viral particles available for productive infection of epithelial target cells in the URT of virus-exposed C-19 vaccinees. Since this leads to a reduced rate of viral shedding in the URT, the viral load transmitted through direct contact with asymptomatically or mildly infected C-19 vaccinees will be relatively low. As a result, the MOI in directly exposed individuals will also be reduced.
Consequently, re-exposure to newly emerging SC-2 variants keeps the MOI of epithelial target cells in the URT of C-19 vaccinees low, despite the increased infectiousness of these lineages. This repeatedly compromises the productivity of viral inter-host transmission1 much more than it affects its efficiency. In other words, lower MOIs associated with more infectious variants keep productive viral infection rates in the URT low while (asymptomatically or mildly) infected individuals can transmit the virus for a prolonged period, thereby ensuring efficient inter-host transmission.
As vaccine breakthrough infections (VBTIs) with more infectious variants come with lower MOIs, the rate of viral adsorption onto URT-patrolling dendritic cells (DCs) will be lowered too, decreasing the binding of (polyreactive) non-neutralizing antibodies (PNNAbs) to DC-tethered virions. It follows that the successive emergence of more infectious variants in highly C-19 vaccinated regions (as depicted in Fig. 4 below) could explain why, despite a substantial increase in the estimated infection rate (see Fig. 2 and % test positivity in Fig. 3) and wastewater activity, ongoing VBTIs will only result in a rather slow increase in collective immune pressure on viral trans infection2. As a result, it requires more time for nature to select lineages that have accumulated the necessary mutations and adaptations that lead to increased virulence. Hence, in the majority of people from highly C-19 vaccinated populations, respiratory symptoms and shedding at the URT are still relatively mild, whereas population-level immune pressure on PNNAb-mediated viral inhibition is slowly increasing due to the gradually decreasing binding of PNNAbs to DC-tethered virions. Reduced binding of these virulence-inhibiting antibodies may explain the current uptick in C-19 hospitalization and death rates (see Fig. 3 below).
Just like in a natural pandemic, we are currently dealing with high virus transmission rates and an increasing number of severe C-19 disease cases. However, whereas in a natural SC-2 pandemic the number of severe cases typically decreases as herd immunity controls virus transmission, the current expectation is that the number of severe cases of disease will only escalate because herd immunity does not develop during an immune escape pandemic, and thus virus transmission continues unchecked and rampant!
This is why I keep saying that societies in highly C-19 vaccinated regions will be caught off guard!
Last but not least, it is interesting to note that newly emerging (sub)variants are increasingly acquiring glycan-based mutations on the N-terminal domain of the spike protein (S-NTD; see: https://x.com/LongDesertTrain/status/1814839721182257211). As previously anticipated (https://www.voiceforscienceandsolidarity.org/scientific-blog/predictions-gvb-on-evolution-c-19-pandemic), this suggests that nature is now favoring glycan-based mutations as a strategy to counteract the suboptimal immune pressure exerted by trans infection-inhibiting PNNAbs (which target a conserved antigenic site within S-NTD) in C-19 vaccinees. These mutations are thought to cause steric hindrance that impedes the binding of PNNAbs to the conserved antigenic site on S-NTD. Once glycan-based mutations become increasingly incorporated into circulating variants, it is highly likely that the virus will largely rely on these mutations to evade the population-level immune pressure affecting its virulence. It's therefore fair to conclude that we're not yet out of the woods!
1 Alike the new, fitter 'riders' taking over thefront of the peloton to decelerate the pace at which the peloton pursues theirbreakaway teammate, newly emerging, more infectious variants decelerate thepace at which the virus productively infects susceptible host cells in the URT(see https://voiceforscienceandsolidarity.substack.com/p/just-as-the-fittest-teammates-of).
2 Viral trans infection refers to the transfer of infectious virions attached to migratory DCs to susceptible target cells in distal organs, including but not limited to the lower respiratory tract. Enhancement of viral trans infection therefore facilitates systemic intra-host transmission of the virus, thereby increasing its virulence.
Geert Vanden Bossche received his DVM from the University of Ghent, Belgium, and his PhD degree in Virology from the University of Hohenheim, Germany. He held adjunct faculty appointments at universities in Belgium and Germany. After his career in Academia, Geert joined several vaccine companies (GSK Biologicals, Novartis Vaccines, Solvay Biologicals) to serve various roles in vaccine R&D as well as in late vaccine development.
Geert then moved on to join the Bill & Melinda Gates Foundation’s Global Health Discovery team in Seattle (USA) as Senior Program Officer; he then worked with the Global Alliance for Vaccines and Immunization (GAVI) in Geneva as Senior Ebola Program Manager. At GAVI he tracked efforts to develop an Ebola vaccine. He also represented GAVI in fora with other partners, including WHO, to review progress on the fight against Ebola and to build plans for global pandemic preparedness.
Back in 2015, Geert scrutinized and questioned the safety of the Ebola vaccine that was used in ring vaccination trials conducted by WHO in Guinea. His critical scientific analysis and report on the data published by WHO in the Lancet in 2015 was sent to all international health and regulatory authorities involved in the Ebola vaccination program. After working for GAVI, Geert joined the German Center for Infection Research in Cologne as Head of the Vaccine Development Office. He is at present primarily serving as a Biotech / Vaccine consultant while also conducting his own research on Natural Killer cell-based vaccines.
Email: info@voiceforscienceandsolidarity.org
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