jueves , 13 febrero 2025

63 estudios vinculan la vacunación contra Covid con la aparición de variantes virales resistentes a las inyecciones

Las variantes surgieron en la proximidad temporal y geográfica de los ensayos clínicos o de las campañas de “vacunación” masiva.

Wang et al. estipularon que, a medida que se generalice la inmunidad global por vacunación o infección previa, se espera que las mutaciones resistentes a las vacunas se conviertan en el factor dominante de la evolución del SARS-CoV-2, lo que permitirá que el virus evada los anticuerpos neutralizantes y persista a pesar de la inmunidad generalizada. Al analizar las trayectorias evolutivas de las mutaciones resistentes a las inyecciones en más de 2,2 millones de genomas del SARS-CoV-2, observaron una fuerte correlación entre la frecuencia de estas mutaciones y las tasas de vacunación en Europa y América:

A continuación se presentan 63 estudios revisados ​​por pares que vinculan la “vacunación” contra COVID-19 con la evolución de variantes virales resistentes a las inyecciones.

La siguiente recopilación de 63 artículos revisados ​​por pares que sugieren que las “vacunas” ejercieron una fuerte presión selectiva sobre el virus SARS-CoV-2, que muta rápidamente, lo que dio lugar rápidamente a variantes resistentes a las “vacunas”. Cabe destacar que las variantes surgieron en proximidad temporal y geográfica a los ensayos clínicos de las “vacunas” o a la “vacunación” masiva:

1. La variante Alfa se identificó por primera vez en el condado de Kent, en el sureste de Inglaterra, en noviembre de 2020. En los ensayos clínicos de fase I/II de la “vacuna” adenovectorial AZD1222 (ChAdOx1 nCoV-19) de AstraZeneca participaron más de 1000 sujetos en el sur de Inglaterra en abril de 2020, y miles más en el ensayo de fase III, de mayo a diciembre de 2020.

2. La variante Delta se identificó por primera vez en el estado de Maharashtra , India, en octubre de 2020. Los ensayos clínicos de fase II/III para la “vacuna” adenovectorial Covidshield basada en AZD1222 de AstraZeneca inscribieron a 1.600 sujetos en 14 centros hospitalarios, incluidos ocho en el estado de Maharashtra , entre julio y octubre de 2020.

3. La variante Ómicron se identificó por primera vez en Gauteng , Sudáfrica, en noviembre de 2021, luego de una intensa campaña de “vacunación” provincial entre agosto y octubre.

En este sentido, los funcionarios de salud pública han advertido que “perseguir variantes” probablemente sea inútil:

  • En enero de 2023, el Dr. Peter Marks, director del Centro de Evaluación e Investigación Biológica de la FDA, escribió : “Continuar por el camino actual de… vacunas de refuerzo específicas para cada variante es inadecuado como estrategia a largo plazo para abordar la COVID-19… Simplemente actualizar las vacunas existentes con nuevas secuencias de variantes o incluso fabricar vacunas trivalentes o cuadrivalentes… no es probable que proporcione la profundidad y amplitud de protección necesarias para interrumpir la transmisión viral”.
  • El Dr. Paul Offit, miembro del Comité Asesor de Vacunas y Productos Biológicos Relacionados (VRBPAC) de la FDA, dijo a Time : “La experiencia del año pasado nos ha enseñado que perseguir estas variantes ómicron con una vacuna bivalente es un juego perdido”.

Lista de estudios

  1. Al-Khatib HA et al., “Comparative analysis of within-host diversity among vaccinated COVID-19 patients infected with different SARS-CoV-2 variants,” iScience, 2022, 25, 11: 105438. doi:
    https://doi.org/10.1016/j.isci.2022.105438
    • “Overall, the relatively higher intra-host diversity among vaccinated individuals and the detection of immune-escape mutations, despite being rare, suggest a potential vaccine-induced immune pressure in vaccinated individuals.”
  2. Atlani-Duault L et al., “Immune evasion means we need a new COVID-19 social contract,” Lancet Public Health 2021, 6, 4: E199-E200. doi: 10.1016/S2468-2667(21)00036-0
    • “… the dynamics of natural or vaccinal collective immunity in the regions where these variants emerged might have placed substantial pressure on the viral ecosystem, facilitating the emergence of a variant with enhanced transmissibility… This virological game changer has numerous consequences, not only for vaccines and treatment, but also for prevention and control strategies. The fervently awaited end of this global health crisis might be continually postponed, as new variants emerge and immune evasion reduces vaccination effectiveness in the short and medium term. Hence, it is time to abandon fear-based approaches based on seemingly haphazard stop-start generalised confinement as the main response to the pandemic; approaches which expect citizens to wait patiently until intensive care units are re- enforced, full vaccination is achieved, and herd immunity is reached.”
  3. Berkhout B and E Herrera-Carrillo, “SARS-CoV-2 Evolution: On the Sudden Appearance of the Omicron Variant,” J. Virol. 2022, 96, 7. doi: https://doi.org/10.1128/jvi.00090-22
    • “The most compelling evidence for this scenario of regular Darwinian evolution actually comes from inspection of the genetic changes, which reveals a profound preference for mutations that change the amino acid composition of the spike protein: 30 nonsilent changes versus 1 silent mutation.”
  4. Brand M and Can Kesmir, “Evolution of SARS-CoV-2-specific CD4+ T cell epitopes,” Immunogent.
    2023, 75: 283-293. doi: https://doi.org/10.1007/s00251-023-01295-8
    • “In this study, we aim to study spike (CD4+) T cell epitopes in silico and investigate the effect of vaccine selection pressure on epitope conservation and mutations in VOCs… we demonstrated in silico that selection induced by vaccination worldwide has marginal effects on SARS-CoV-2 spike-specific CD4 T cell responses, while this might be not at all the case for B cell responses. Therefore, it might be worthwhile to consider inclusion of other less mutating SARS- CoV-2 proteins such as ORF3, NSP3, and the N protein in a future vaccine.”
  5. Brandolini M et al., “Omicron Sub-Lineage BA.5 and Recombinant XBB Evasion from Antibody Neutralisation in BNT162b2 Vaccine Recipients,” Microorganisms 2023, 11, 1: 191.
    doi: https://doi.org/10.3390/microorganisms11010191
    • “These evolutionary characteristics have prompted intensively debated questions and speculations, primarily regarding how vaccines will contribute to the emergence of new variants.
    Moreover, as many vaccines are based on the ancestral Spike protein gene sequence, they elicit a relatively ‘narrow-spectrum’ immune response, which can be easily and rapidly eroded by viral evolution. In fact, there is emerging evidence that the high mutation rate of the S gene constitutes a breeding ground for immune escape mechanisms, reducing the neutralising potential of antibodies produced in vaccinated subjects.”
  6. Bushman M et al., “Population impact of SARS-CoV-2 variants with enhanced transmissibility and/or partial immune escape,” Cell 2021, 184, 26: P6229-6242.E18. doi: 10.1016/j.cell.2021.11.026
    • “Here, we use a mathematical model to simulate the dynamics of wild-type and variant strains of SARS-CoV-2 in the context of vaccine rollout and nonpharmaceutical interventions. We show that variants with enhanced transmissibility frequently increase epidemic severity, whereas those with partial immune escape either fail to spread widely or primarily cause reinfections and breakthrough infections. However, when these phenotypes are combined, a variant can continue spreading even as immunity builds up in the population, limiting the impact of vaccination and exacerbating the epidemic.”
  7. Cao Y et al., “Imprinted SARS-CoV-2 humoral immunity induces convergent Omicron RBD
    evolution,” Nature 2023, 614: 521–529. doi: https://doi.org/10.1038/s41586-022-05644-7
    • “In this work, we showed that due to immune imprinting, our humoral immune repertoire is not effectively diversified by infection with new Omicron variants. The immune pressure on the RBD becomes increasingly concentrated and promotes convergent evolution, explaining the observed sudden acceleration of SARS-CoV-2 RBD evolution and the convergence pattern.
    Although this study only examines inactivated vaccines, immune imprinting is also observed in those receiving mRNA vaccines.”
  8. Carabelli AM et al., “SARS-CoV-2 variant biology: immune escape, transmission and fitness,” Nat
    Rev Microbiol 2023, 21, 162–177. doi: https://doi.org/10.1038/s41579-022-00841-7.
    • “The increased virus fitness associated with VOCs is the result of a complex interplay of virus
    biology in the context of changing human immunity due to both vaccination and prior infection.”
  9. Chaguza C et al., “Rapid emergence of SARS-CoV-2 Omicron variant is associated with an infection advantage over Delta in vaccinated persons,” Clin. Transl. Rep. 2022, 3, 5: P325-334.E4.
    doi: 10.1016/j.medj.2022.03.010
    • “As population immunity to SARS-CoV-2 increases through infections and vaccination, selection for variants that are partially resistant to the immune response, in particular neutralizing antibodies, should also increase… We hypothesized that the rapid emergence and spread of the SARS-CoV-2 Omicron variant was partly due to its increased ability to evade immunity from prior infection and/or vaccination. Using a study population seeking outpatient testing when Omicron and Delta were overall relatively equal among infections, we found that Omicron has a relatively higher propensity to cause infections in COVID-19-vaccinated persons.”
  10. Chang MR et al., “Analysis of a SARS-CoV-2 convalescent cohort identified a common strategy for escape of vaccine-induced anti-RBD antibodies by Beta and Omicron variants,” eBioMedicine 2022, 80: 104025. doi: 10.1016/j.ebiom.2022.104025
    • “Structural analysis of the Beta and Omicron RBDs reveal a shared immune escape strategy involving residues K417-E484-N501 that is exploited by these variants of concern… Through mutations of the K417-E484-N501 triad, SARS-CoV-2 has evolved to evade neutralization by the class I/II anti-RBD antibody fraction of hybrid immunity plasma as the polyclonal antibody response post-vaccination shows limitations in the ability to solve the structural requirements to bind the mutant RBDs.”
  11. Cocherie T et al., “Epidemiology and Characteristics of SARS-CoV-2 Variants of Concern: The Impacts of the Spike Mutations,” Microorganisms 2023, 11, 1: 30. doi:
    https://doi.org/10.3390/microorganisms11010030
    • “Following the spread of lineage B.1, new lineages emerged in a context of selection pressure related to the extension of vaccination and post-infectious immunization. These lineages have each selected specific sets of mutations, in an asynchronous and geographically isolated manner, which supports the hypothesis of a convergent antigenic evolution, reinforced by the discovery of some of their mutations in independent lineages.”
    12. Collier DA et al., “Sensitivity of SARS-CoV-2 B.1.1.7 to MRNA vaccine-elicited antibodies,” Nature 2021, 593: 136–141. doi: https://doi.org/10.1038/s41586-021-03412-7
    • “Taken together, the presence of multiple escape mutations in the NTD is supportive of the hypothesis that this region of the spike, in addition to the RBM, is also under immune pressure… Our data suggest that vaccine escape by the virus of current spike-directed vaccines designed against the Wuhan-1 strain will be inevitable…”
  12. Day T et al., “Pathogen evolution during vaccination campaigns,” PLoS Biol 2022, 20, 9: e3001804.
    doi: https://doi.org/10.1371/journal.pbio.3001804
    • “…vaccine-driven evolution has tended to occur in other pathogens when either the benefits of< prophylaxis are small (e.g., the vaccine does not sufficiently suppress pathogen replication below transmissible levels) or when they target a small number of pathogen epitopes. Data increasingly suggest that at least the first of these is true for SARS-CoV-2 and currently deployed vaccines.”
  13. Dijokaite-Guraliuc A et al., “Rapid escape of new SARS-CoV-2 Omicron variants from BA.2-directed antibody responses,” Cell Rep. 2023, 42, 2: 112271. doi: 10.1016/j.celrep.2023.112271
    • “Overall, in line with the observations on the set of mAbs described above, there were large reductions in neutralization titers against most BA.2 sub-lineages, particularly BA.2.75.2, BA.2.3.20, BQ.1, and XBB, suggesting that they have been selected to escape pre-existing immunity to vaccines or earlier waves of SARS-CoV-2 infection… It is likely that evolution of SARS-CoV-2 Omicron is now primarily driven by extreme pressure to escape antibody responses in vaccinated and/or naturally infected individuals, with compensatory mutations to maintain or increase ACE2 affinity.”
  14. Duerr R et al., “Dominance of Alpha and Iota variants in SARS-CoV-2 vaccine breakthrough infections in New York City,” J Clin Invest 2021, 131, 18: e152702. Doi: 10.1172/JCI152702
    • “Despite the overall effectiveness of vaccination, our full spike mutation analysis revealed a broad set of spike mutations (n = 23) to be elevated in the vaccine breakthrough group. The analysis indicates that adaptive selection is in progress that may subsequently come into full effect.”
  15. Duerr R et al., “Selective adaptation of SARS-CoV-2 Omicron under booster vaccine pressure: a multicentre observational study,” eBioMedicine 2023, 97: 104843.
    doi: 10.1016/j.ebiom.2023.104843
    • “Booster shots are required to cope with gaps in immunity. Their discriminative immune pressure contributes to their effectiveness but also requires monitoring of selective viral adaptation processes. Omicron BA.2 and BA.5 had a selective advantage under booster vaccination pressure, contributing to the evolution of BA.2 and BA.5 sublineages and recombinant forms that predominate in 2023.”
  16. Fang FF and Pei-Yong Shi, “Omicron: a drug developer’s perspective,” Emerg. Microbes & Infect.
    2022, 11, 1. doi: https://doi.org/10.1080/22221751.2021.2023330
    • “Omicron has revealed to us that SARS-CoV-2 has the potential to go beyond the protective threshold provided by vaccines and antibodies. Playing catchup to SARS-CoV-2 selects for more resistant and transmissible variants and may not be successful in the long run.”
  17. Focosi D et al., “Convergent Evolution in SARS-CoV-2 Spike Creates a Variant Soup from Which New
    COVID-19 Waves Emerge,” Int. J. Mol. Sci. 2023, 24, 3: 2264.
    doi: https://doi.org/10.3390/ijms24032264
    • “The most likely reason for this convergence is the selective pressure exerted by previous infection- or vaccine-elicited immunity… The combined action of increasing cumulative viral loads in the ‘human culture medium’ and such selective pressures has led to an unprecedented increase in viral diversification in 2022.”
  18. Garcia-Beltran WF et al., “Multiple SARS-CoV-2 variants escape neutralization by vaccine-induced
    humoral immunity,” Cell 2021, 184, 9: p2372-2383.e9. doi: 10.1016/j.cell.2021.03.013
    • “… we found that B.1.351 variants exhibited remarkable resistance to neutralization, largely due to three mutations in RBD but with measurable contribution from non-RBD mutations. The magnitude of the effect is such that B.1.351 strains escaped neutralizing vaccine responses as effectively as distantly related coronaviruses.”
  19. Gayvert K et al., “Evolutionary trajectory of SARS-CoV-2 genome shifts during widespread vaccination and emergence of Omicron variant,” npj Viruses 2023, 1: 5. doi:
    https://doi.org/10.1038/s44298-023-00007-z
    • “Our analysis revealed that during the first year of the pandemic (2020 to 2021), the SARS-CoV-2 genome was subject to strong conservation… However, we observed a sharp increase in the diversification of the RBD during 2021 (8.1% of sites under diversifying pressure up to 2022), indicating selective pressures that promote the accumulation of mutations. This period coincided with broad viral infection and adoption of vaccination worldwide, and we observed the acquisition of mutations that later defined the Omicron lineages in independent SARS-CoV-2 strains…”
  20. Ghmire D et al., “Structural Plasticity and Immune Evasion of SARS-CoV-2 Spike Variants,”
    Viruses 2022, 14, 6: 1255. doi: https://doi.org/10.3390/v14061255
    • “SARS-CoV-2 viruses are under increased selection pressure from the vaccines, therapeutic approaches, and the host immune system. Whole-genome sequencing technology has allowed identifying the emergence of different SARS-CoV-2 variants… These variants are more transmissible and possibly more pathogenic and immune–evasive. They carry accumulated mutations in the S protein. The resulting amino acid substitutions in S can impact the binding capacity to hACE2 and antibody recognition, therefore imposing constant challenges in current vaccine and therapeutic regimes.”
  21. Gobeil SMC et al., “Effect of natural mutations of SARS-CoV-2 on spike structure, conformation, and
    antigenicity,” Science 2021, 373, 6555. doi: 10.1126/science.abi6226
    • “Although many of the currently circulating variants of interest/concern likely arose from some combination of genetic drift, host adaptation, and immune evasion, the virus will increasingly experience pressure from vaccine-elicited antibody responses.”
  22. Habib MT et al., “Natural selection shapes the evolution of SARS-CoV-2 Omicron in Bangladesh,”
    Front. Genet. 2023, 14 (Sec. Computational Genomics). doi:
    https://doi.org/10.3389/fgene.2023.1220906
    • “We found evidence of adaptive evolution within the spike (S) gene of SARS-CoV-2 Omicron isolated from Bangladesh. In total, 22 codon sites of the S gene displayed a signature of positive selection… Moreover, the lack of selection pressure on the S gene representing SARS-CoV-2 Delta from Bangladesh indicates a possible correlation between vaccination and adaptive evolution.”
  23. Hamburg M and GA Poland, “The time is now for committed and comprehensive action to attain
    more broadly protective coronavirus vaccines: The coronavirus vaccines R&D roadmap,” Vaccine 2023, 41, 16: 2645-2647. doi: https://doi.org/10.1016/j.vaccine.2023.02.053
    • “… we continue to face continued circulation and evolution of SARS-CoV-2 viruses that mutate to evade immune responses among hosts who have partial or waning vaccine coverage, further exacerbating the situation.”
    25. Han W et al., “Predicting the antigenic evolution of SARS-COV-2 with deep learning,” Nat Comm
    2023, 14: 3478. doi: https://doi.org/10.1038/s41467-023-39199-6
    • “We hypothesized that under high immune pressure, the virus would tend to escape the antibody neuralization over a short-term time scale, and therefore the forecasting problem transforms into a search problem: starting from an initial sequence, it searches for a variant sequence within some edit distance range that has an improved antibody escape potential without losing much ACE2-binding ability… These findings verify our assumptions: under the immune selection pressure, the virus evolves in the direction of immune escape, and our model can capture the antibody escape potential of the viral variants.”
  24. Harvey WT et al., “SARS-CoV-2 variants, spike mutations and immune escape,” Nat Rev
    Microbiol 2021, 19: 409–424. doi: https://doi.org/10.1038/s41579-021-00573-0
    • “Given that therapeutics (vaccines and antibody-based therapies) target mainly the SARS-CoV-2
    spike protein, the selection pressures that favour the emergence of new variants carrying
    immune escape mutations generated in chronic infection will be similar to those selecting for
    mutations that allow reinfections within the wider population.”
  25. He P et al., “SARS-CoV-2 Delta and Omicron variants evade population antibody response mutations in a single spike epitope,” Nat. Microbiol. 2022, 7: 1635-1649. doi:
    https://doi.org/10.1038/s41564-022-01235-4
    • “Owing to immune pressure induced by natural infection and vaccination, numerous SARS-CoV-2 variants have emerged, these variants encoding spike proteins with substituted amino acids that function to evade antibody neutralization… Here we identify an important role for VH1-69 HCDR2 in anti-SARS-CoV-2 immunity… These mutation ‘hot spots’ should be continuously monitored and future studies should address the potential pathogenic consequences of VH1-69 antibody evasion by SARS-CoV-2.”
  26. Jankowiak M et al., “Inferring selection effects in SARS-CoV-2 with Bayesian Viral Allele Selection,”
    PLoS Genet. 2022, doi: https://doi.org/10.1371/journal.pgen.1010540
    • “… we conduct an analysis that allows for vaccination-dependent selection effects and find tantalizing evidence that S:N501Y exhibits vaccination-dependent differential fitness… The elevated contribution of S-gene mutations (notably in the RBD) over non-S-gene mutations starting around November 2021 is apparent. Collectively these two results suggest that immune escape has become an increasingly prominent factor in SARS-CoV-2 evolution over time, likely a result of rising rates of convalescent and vaccine-induced immunity to Spike.”
  27. Jena D et al., “Impact of vaccination on SARS-CoV-2 evolution and immune escape variants,”
    Vaccine 2024, 42, 21: https://doi.org/10.1016/j.vaccine.2024.07.054
    • “Our comparative analysis revealed a significant higher incidence of intra-host single nucleotides variants (iSNVs) in vaccinated cases compared to unvaccinated ones (p value<0.0001). Furthermore, we have found that specific mutational processes, including APOBEC (C > T) mediated and ADAR1 (A > G) mediated mutations, were found more prevalent in vaccinated cases. Vaccinated cases exhibited higher accumulation of nonsynonymous mutation than unvaccinated cases… Our findings suggest that vaccine plays an important role in the evolution of the virus genome.”
  28. Kennedy DA and AF Read, “Monitor for COVID-19 vaccine resistance evolution during clinical trials,”
    PLoS Biol. 2020, 18, 11: e3001000. doi: https://doi.org/10.1371/journal.pbio.3001000 31. Konishi T, “Mutations in SARS-CoV-2 are on the increase against the acquired immunity,” PLoS One 2022, 17, 7: e0271305. doi: https://doi.org/10.1371/journal.pone.0271305
    • “In Omicron, there was a high density of S mutations suggesting that there was selection pressure to avoid the acquired immunity imparted by monovalent vaccines… These findings suggest that the early mRNA vaccine has lost its effectiveness. Accordingly, the sixth peak in Japan is becoming extremely high without subsiding, which can be due to dependency of the government only on the vaccines.”
  29. Koyoma T et al., “Evasion of Vaccine-Induced Humoral Immunity by Emerging Sub-Variants of SARS-CoV-2,” Future Microbiol. 2022, 17, 6: 417-424. doi: https://doi.org/10.2217/fmb-2022-0025
    • “… the selection pressure exerted by vaccines might pave the way for other escape mutants in the near future.”
  30. Kumar N et al., “Bayesian Molecular Dating Analyses Combined with Mutational Profiling Suggest an Independent Origin and Evolution of SARS-CoV-2 Omicron BA.1 and BA.2 Sub-Lineages,”
    Viruses 2022, 14, 12: 2764. doi: https://doi.org/10.3390/v14122764
    • “Nonetheless, in the event of the emergence of multiple new mutations in the Omicron’s spike protein, which are quite distinct in the BA.1 and BA.2 sub-lineages, as well as their estimated separate most recent common ancestor, it may be more plausible to conclude that a combination of RBD- and NTD-directed classes of antibody therapeutics at sub-optimal doses in COVID-19 patients or optimal doses in an immunocompromised patient or waned vaccine-induced immunity may have provided a conducive environment to accumulate multiple mutations in Omicron’s spike protein.”
  31. Kumar SW et al., “Vaccine-elicited immune pressure and SARS-CoV-2 mutational dynamics in breakthrough infections,” Gene Rep. 2024, 35: 101899. doi:
    https://doi.org/10.1016/j.genrep.2024.101899
    • “Vaccinated individuals exhibit significantly higher mutation rates, including immune escape mutations… Selection pressure may drive viral mutations for enhanced immune evasion.”
  32. Lewnard JA et al., “Increased vaccine sensitivity of an emerging SARS-CoV-2 variant,” Nat Commun 2023, 14: 3854. doi: https://doi.org/10.1038/s41467-023-39567-2
    • “Immunological and evolutionary factors driving this apparent bifurcation in evasion of vaccine-derived and infection-derived responses for XBB/XBB.1.5 merit further investigation. Notably, vaccinations available in the US (mRNA-1273, BNT162b2, Ad.26.COV2.S, and NVX-CoV2373) target only the SARS-CoV-2 spike antigen. In contrast, infection with SARS-CoV-2 induces responses against an array of SARS-CoV-2 antigens, some of which may be independently associated with protection.”
  33. Li X, “Omicron: Call for updated vaccines,” J. Med. Virol. 2022, 94, 4: 1261-1263. doi:
    https://doi.org/10.1002/jmv.27530
    • “The Omicron SARS-CoV-2 variant was potentially generated from a chronically infected COVID-19 patient vaccinated with an messenger RNA (mRNA)- or non-mRNA-based vaccine, offering the opportunity for the virus to evolve and mutate to evade the body’s immune response. To understand the significance of this SARS-CoV-2 variant and what it means for the global response to the pandemic, vaccinologists should systematically evaluate the role of mRNA- and non-mRNA-based vaccines in the generation of novel SARS-CoV-2 variants, including variants of concerns (VOCs) and interest (VOIs), that occur via breakthrough vaccine-elicited immunity.”
  34. Lomoio U et al., “SARS-CoV-2 protein structure and sequence mutations: Evolutionary analysis and effects on virus variants,” PLoS One 2023, 18, 7: e0283400. doi:
    https://doi.org/10.1371/journal.pone.0283400
    • “We explore patterns of changes in a temporal dimension and compare the cumulative distribution of vaccination with the characteristics of the variant. Although we cannot infer any causality regarding vaccination driving the evolution, we should note that the presence of vaccinations in a timeline is located in the middle of the first variants of SARS-CoV-2 and Omicron. Considering also the clinical characteristics of Omicron in terms of vaccine escape and neutralization of immune response, we can assume that the effect of all Omicron changes may be related to the structural changes also revealed by the above-reported measures.”
  35. López-Cortés GI et al., “The Spike Protein of SARS-CoV-2 Is Adapting Because of Selective Pressures,” Vaccines 2022, 10, 6: 864. doi: https://doi.org/10.3390/vaccines10060864
    • “Our results hint that selective pressures are induced by mass vaccination throughout the world and by the persistence of recurrent infections in immunosuppressed individuals, who did not eliminate the infection and ended up facilitating the selection of viruses whose characteristics are different from the previous VOCs, less pathogenic but with higher transmissibility.”
  36. Magazine N et al., “Mutations and Evolution of the SARS-CoV-2 Spike Protein,” Viruses 2022, 14, 3):
    1. doi: https://doi.org/10.3390/v14030640
      • “Taken together with the fact that many of these mutations occur within the Omicron variant (which appeared only after vaccinations became widely distributed), it is possible that resistance to neutralizing antibodies (particularly those found in postvaccinated sera) targeting the NTD play a large role in the positive selection for SARS-CoV-2… Mutations within the S protein of the circulating variants of SARS-CoV-2 are increasing at a significant rate and are likely to occur more often as selective pressures from host immunity gained in previous infections and/or vaccinations continue to drive rapid evolution.”
  37. Mahroum N et al., “Vaccine-induced strain replacement: theory and real-life implications,” Future
    Microbiol. 2024, 19, 11: 1017-1026. doi: https://doi.org/10.1080/17460913.2024.2345003
    • “… increasing fitness of nonvaccine strains and metabolic shifts in the subtypes have been described. Classical examples include pneumococcal infections and viral diseases, such as the human papilloma virus… The recent SARS-CoV-2 virus responsible for the COVID-19 pandemic has been correlated to the vaccine-induced pathogen strain replacement.”
  38. Martin DP et al., “Selection Analysis Identifies Clusters of Unusual Mutational Changes in Omicron Lineage BA.1 That Likely Impact Spike Function,” Mol Biol Evol 2022, 39, 4: msac061. doi:
    https://doi.org/10.1093/molbev/msac061
    • “Given the evident epidemic growth advantages of Omicron overall previously known SARS-CoV-2 lineages, it is crucial to determine both how such complex and highly adaptive mutation constellations were assembled within the Omicron S-gene, and why, despite unprecedented global genomic surveillance efforts, the early stages of this assembly process went completely undetected.”
  39. McLeod DV and S Gandon, “Effects of epistasis and recombination between vaccine-escape and virulence alleles on the dynamics of pathogen adaptation,” Nat Ecol Evol 2022, 6: 786–793. doi:
    https://doi.org/10.1038/s41559-022-01709-y
    • “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.”
  40. Meganck RM et al., “SARS-CoV-2 variant of concern fitness and adaptation in primary human airway epithelia,” Cell Rep. 2024, 43, 4: 114076. doi: 10.1016/j.celrep.2024.114076
    • “… the Omicron variant emerged in November of 2021, at which point ∼4 billion people are believed to have been vaccinated and more were likely to have been previously infected. The greater level of population immunity likely constituted a selective pressure on the virus. The newly emerged Omicron BA.1 strains contained a greater proportion of viral mutations located in the spike protein, the major antigenic target of SARS-CoV-2 adaptive immune responses, as compared to previous variants.”
  41. Messali S et al., “Emergence of S gene-based quasispecies explains an optimal adaptation of Omicron BA.5 subvariant in the immunocompetent vaccinated human host,” J Med Virol. 2023, 95,
    1: e28167. doi: https://doi.org/10.1002/jmv.28167
    • “The low frequency of quasispecies observed in BA.2.3- and BA.5-infected patients supports the hypothesis that these omicron sub-lineages are adapted to vaccine-elicited immune responses.”
  42. Mussò N et al., “SARS-CoV-2’s high rate of genetic mutation under immune selective pressure: from oropharyngeal B.1.1.7 to intrapulmonary B.1.533 in a vaccinated patient,” Int. J. Infect. Dis. 2022,
    118: 169-172. doi: https://doi.org/10.1016/j.ijid.2022.02.044
    • “The immune reaction was a combination of vaccine and immune response after infection with SARS-CoV-2, but the presence of antibodies did not lead to the disruption of the viral RNA before this could cause pulmonary infection; on the contrary, it accelerated the normal process of “intra-host specific rearrangement,” as shown by the presence of a new intra-pulmonary lineage characterized by 5 worldwide low-expressed SNPs…”
  43. Nabel KA et al., “Structural basis for continued antibody evasion by the SARS-CoV-2 receptor binding domain,” Science 2021, 375, 6578. doi: 10.1126/science.abl6251
    • “As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replicates under selective pressure from natural and vaccine-induced immunity, variants of concern (VOCs) continue to emerge. Through adaptative evolution, these variants acquire mutations in the spike protein receptor binding domain (RBD) that binds the cellular receptor angiotensin-converting enzyme 2 (ACE2)… We find that accumulation of large numbers of RBD mutations is facilitated by structural plasticity at the RBD–ACE2 interface and further erodes the activity of therapeutic antibodies and serum from vaccine recipients. Furthermore, acquisition of an N-linked glycan on the SARS-CoV-2 RBD is an additional neutralization escape pathway that should be closely monitored during viral antigenic drift.”
  44. Oliviera JR et al., “Immunodominant antibody responses directed to SARS-CoV-2 hotspot mutation sites and risk of immune escape,” Front. Immunol. 2023, 13 (Sec. Viral Immunology). doi:
    https://doi.org/10.3389/fimmu.2022.1010105
    • “Our results showed that amongst convalescents a more focused response, with fewer peptides being recognized, was associated with higher neutralization titers. We reason that immune pressure following vaccination contributed to epitope spreading and likely surge of omicron that presents several mutations at RBD and the capacity of escaping antibody neutralization.”
  45. Rolland M and PB Gilbert, “Sieve analysis to understand how SARS-CoV-2 diversity can impact vaccine protection,” PLoS Pathog. 2021, 17, 3: e1009406. doi:
    https://doi.org/10.1371/journal.ppat.1009406
    • “The recent spread of outlier variants emphasizes the need to rapidly track the impact of vaccine-induced pressure on SARS-CoV-2 evolution… The variants B.1.1.7 (originally identified in the UK), B.1.351 (originally identified in South Africa), and P.1 (originally identified in Brazil) have more mutations than what was expected at this time in the pandemic, and a large fraction of these mutations are in the Spike, indicating likely selection pressure behind their emergence… . The selective pressure exerted by the vaccine together with limited vaccine< coverage in the population has the potential to open ecological niches where rare variants with potentially unfavorable resistance profiles could outcompete circulating viruses.”
  46. Rouzine IM and G Rozhnova, “Evolutionary implications of SARS-CoV-2 vaccination for the future design of vaccination strategies,” Commun. Med 2023, 3, 86. doi: https://doi.org/10.1038/s43856-023-00320-x
    • “Mass vaccination, as we show below, might increase this pressure and accelerate SARS-CoV-2 evolution in spike epitopes compared to natural infection.”
  47. Sanyaolu A et al., “SARS-CoV-2 Omicron variant (B.1.1.529): A concern with immune escape,” World
    J Virol 2022, 11, 3:137–143. doi: 10.5501/wjv.v11.i3.137
    • “Finally, it has been proposed that natural selection can arise as a result of mutations that increase viral infectivity, antibody resistance, and vaccine breakthrough. Evolutionary descent of the Omicron lineages showed that mutations arose under selection pressure due to antibodies elicited by infection, vaccination, or both, in the human population on a large scale.”
  48. Servellita V et al., “Predominance of antibody-resistant SARS-CoV-2 variants in vaccine breakthrough cases from the San Francisco Bay Area, California,” Nat Microbiol 2022, 7, 277-288.
    doi: https://doi.org/10.1038/s41564-021-01041-4
    • “The predominance of immune-evading variants among post-vaccination cases indicates possible selective pressure for antibody-resistant escape variants circulating locally over time in the vaccinated population.”
  49. Tan CW et al., “SARS-CoV-2 Omicron variant emerged under immune selection,” Nat Microbiol 2022, 7: 1756–1761. doi: https://doi.org/10.1038/s41564-022-01246-1
    • “Using the same serum panels, we demonstrated even more potent NAb escape of mRNA vaccine-induced neutralizing antibodies by Omicron subvariants BA.2.11 and BA.5 with the additional L452R mutation and L452R/F486V/R493Q mutations, respectively… We propose that the SARS-CoV-2 Omicron variant emerged under immune selection imposed during 2 years of virus transmission in humans.”
  50. Vanden Bossche G, floor letter to the Oregon State Legislature, “The Science behind the Catastrophic Consequences of Thoughtless Human Intervention in the Covid-19 Pandemic,” March 13, 2021, https://olis.oregonlegislature.gov/liz/2021R1/Downloads/FloorLetter/3166
    • “Why are the Covid-19 vaccines likely to enhance viral infectiousness? It’s because they are prophylactic vaccines – designed to build immunity in individuals before they get exposed to the pathogen/virus. They are not suitable at all for administration to people during a pandemic… Exerting high immune pressure without preventing viral replication and transmission is a recipe for selective viral immune escape.”
  51. van Dorp CH et al., “Estimating the strength of selection for new SARS-CoV-2 variants,”
    Nat Commun 2021, 12: 7239. doi: https://doi.org/10.1038/s41467-021-27369-3
    • “… the gradual rollout of vaccination programs globally is changing the immunological landscape, possibly leading to the emergence of escape strains that are partially or fully resistant to existing vaccines… Integrating molecular epidemiology surveillance into SARS-CoV-2 pipelines is essential for not only monitoring the emergence of new strains, but for establishing an early warning system to monitor for escape mutations in the era of vaccine rollout.”
  52. van Egeren D et al., “Risk of rapid evolutionary escape from biomedical interventions targeting SARS-CoV-2 spike protein,” PLoS One 2021, 16, 4: e0250780. doi:
    https://doi.org/10.1371/journal.pone.0250780
    • “Our modeling suggests that SARS-CoV-2 mutants with one or two mildly deleterious mutations are expected to exist in high numbers due to neutral genetic variation, and consequently resistance to vaccines or other prophylactics that rely on one or two antibodies for protection can develop quickly -and repeatedly- under positive selection.”
  53. Wang Q et al., “Alarming antibody evasion properties of rising SARS-CoV-2 BQ and XBB subvariants,”
    Cell 2023, 186, 2: P279-286.E8. doi: 10.1016/j.cell.2022.12.018
    • “Together, our findings indicate that BQ and XBB subvariants present serious threats to current COVID-19 vaccines, render inactive all authorized antibodies, and may have gained dominance in the population because of their advantage in evading antibodies.”
  54. Wang R et al., “Emerging Vaccine-Breakthrough SARS-CoV-2 Variants,” ACS Infect. Dis. 2022, 8, 3:
    546–556. doi: https://doi.org/10.1021/acsinfecdis.1c00557
    • “We show that prevailing variants can be quantitatively explained by infectivity-strengthening and vaccine-escape (co-)mutations on the spike protein RBD due to natural selection and/or vaccination-induced evolutionary pressure. We illustrate that infectivity strengthening mutations were the main mechanism for viral evolution, while vaccine-escape mutations become a dominating viral evolutionary mechanism among highly vaccinated populations… We foresee an urgent need to develop new virus combating strategies.”
  55. Wang R et al., “Mechanisms of SARS-CoV-2 Evolution Revealing Vaccine-Resistant Mutations in Europe and America,” J. Phys. Chem. Lett. 2021, 12, 49: 11850–11857. doi:
    https://doi.org/10.1021/acs.jpclett.1c03380
    • “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.”
  56. Wang Z et al., “mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants,”
    Nature 2021, 592: 616–622. doi: https://doi.org/10.1038/s41586-021-03324-6
    • “Nevertheless, emergence of these particular variants is consistent with the dominance of the class-1 and -2 antibody response in infected or vaccinated individuals. We speculate that these mutations emerged in response to immune selection in individuals with nonsterilizing immunity.”
  57. Yang Z et al., “SARS-CoV-2 Variants Increase Kinetic Stability of Open Spike Conformations as an Evolutionary Strategy,” mBio 2022, 13, 1. doi: https://doi.org/10.1128/mbio.03227-21
    • “Under the selection pressure imposed by adaptation to the human host and increasing vaccinations and convalescent patients, SARS-CoV-2 is evolving and has adopted numerous mutations on S variants. These promote virus spreading and immune evasion, partially by increasing the propensity of S to adopt receptor-binding competent open conformations.”
  58. Zhang Y et al., “Vaccination Shapes Within-Host SARS-CoV-2 Diversity of Omicron BA.2.2 Breakthrough Infection,” J. Infect. Dis. 2024, 229, 6: 1711-1721. doi:
    https://doi.org/10.1093/infdis/jiad572
    • “The enrichment of mutations in the spike protein gene indicates selection pressure exerted by vaccination on the evolution of SARS-CoV-2.”
  59. Zhao H et al., “VOC-alarm: mutation-based prediction of SARS-CoV-2 variants of concern,”
    Bioinform. 2022, 38, 14: 3549-3556. doi: https://doi.org/10.1093/bioinformatics/btac370
    • “We compared the paces of the evolution that caused the speedy mutation of the VOCs in Stages I, III, V and VII (predicted for Omicron). From Alpha to Delta, the pace of evolution was significantly decreased… which might be related to the fast rollouts of vaccines in late 2020 and early 2021. However, from Delta to Delta plus and Omicron, the pace of evolution has been significantly increased… This might be associated with the adaptiveness of the new VOCs to the selective pressures caused by vaccines.”
  60. Zhou D et al., “Evidence of escape of SARS-CoV-2 variant B.1.351 from natural and vaccine-induced sera,” Cell 2021, 184, 9: p2348-2361.e6. doi: 10.1016/j.cell.2021.02.037
    • “The ACE2-binding surface is to some extent the Achilles heel of the virus as it can be blocked by some neutralizing antibodies; however, since it is so small, it also threatens immune escape, as small changes can throw off neutralizing antibodies, thereby reducing the ability of natural or vaccine-acquired immunity to contain viral replication. Selective pressure for changes in the ACE2 interaction surface can thus have two entirely separate drivers. First, as SARS-CoV-2 has recently crossed a zoonotic barrier, it may be expected that evolution of the ACE2 interaction surface may occur to increase affinity to ACE2 and thereby increase viral transmissibility. And second, conversely, changes to the ACE2 interaction surface may also reduce the protection afforded by previous infection or vaccination, potentially leading to escape from pre-existing immunity induced by natural infection or vaccines.”

Colabore por favor con nosotros para que podamos incluir mas información y llegar a más personas: contribución en mercado pago o paypal por única vez, Muchas Gracias!

10.000$ar https://mpago.la/1srgnEY
5.000$ar https://mpago.la/1qzSyt9
1.000$ar  https://mpago.la/1Q1NEKM
Via PAYPAL: Euros o dólares click aqui
Solicite nuestro CBU contactenos