April 28, 2024

Within-host versus within-population selection pressure

Within-host selection pressure does NOT dictate viral evolution and thus does not correlate with the emergence of SARS-CoV-2 variants in highly Covid-19 vaccinated populations.

Contrary to the implications of this publication (, studying within-host diversity of SARS-CoV-2 (SC-2) may not always be a scientifically robust approach for investigating viral evolution, especially in the context of mass vaccination against a virus causing acute self-limiting infection (ASLI) or during subsequent vaccine breakthrough infections (VBTIs), such as those caused by Omicron.

In highly Covid-19 (C-19) vaccinated populations, the evolutionary trajectory and dynamics of ASLI-causing viruses are primarily shaped by the immune selection pressure exerted by the entire vaccinated population on viral infectiousness or transmissibility, rather than by individual vaccinated hosts. In other words, the within-host mutation rate does not reflect the impact of mass vaccination or widespread VBTIs. Cross-neutralizing antibodies generated in response to VBTIs caused by Omicron target more conserved antigenic domains within the spike protein and thereby constrain the mutation rate within a single C-19 vaccinated host while driving large-scale immune evasion at the population level within highly C-19 vaccinated populations.

The population-level immune selection pressure on the virus persists as long as herd immunity is not achieved.

In conclusion, since the emergence of Omicron, within-population selection pressure has driven the widespread emergence and co-circulation of a diversified spectrum of immune escape variants within highly C-19 vaccinated populations.

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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.


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