Cited by 557SARS-CoV-2 and COVID-19 ResearchImmune responses and vaccinationsvaccines and immunoinformatics approaches

mRNA vaccination boosts cross-variant neutralizing antibodies elicited by SARS-CoV-2 infection

Open access
Stamatatos, Leonidas, Czartoski, Julie, Wan, Yu-Hsin, Homad, Leah J., Rubin, Vanessa, Glantz, Hayley, Neradilek, Moni, Seydoux, Emilie +11 more·2021·Science

Published version of a preprint

Abstract

Boosterism could save lives: Postinfection immune protection against severe acute respiratory syndrome coronavirus 2 reinfection is not fully understood. It will be devastating if waves of new variants emerge that undermine natural immune protection. Stamatatos et al. investigated immune responsiveness 4 to 8 months after previously infected individuals were given a messenger RNA–based vaccine developed for the original Wuhan variant (see the Perspective by Crotty). Before vaccination, postinfection serum antibody neutralization responses to virus variants were variable and weak. Vaccination elevated postinfection serum-neutralizing capacity approximately 1000-fold against Wuhan-Hu-1 and other strains, and serum neutralization against the variant B.1.351 was enhanced. Although responses were relatively muted against the variant, they still showed characteristic memory responses. Vaccination with the Wuhan-Hu-1 variant may thus offer a valuable boost to protective responses against subsequent infection with variant viruses. Science , abg9175, this issue p. 1413 ; see also abj2258, p. 1392

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Written from the paper’s full text.

TL;DR

In previously SARS-CoV-2–infected donors, a single mRNA vaccine dose boosted neutralizing antibody titers ~1000-fold against Wuhan-Hu-1 and also increased cross-neutralization of B.1.351 variants, though titers against divergent variants were lower. The boost depended on preexisting RBD-specific immunological memory and was largely mediated by anti-RBD antibodies.

Key findings

  • Before vaccination, postinfection serum neutralization was variable and weak: 12 of 15 previously infected donors (PIDs) neutralized Wuhan-Hu-1, 5 of 15 neutralized B.1.351, and 7 of 15 neutralized B.1.351–Δ242-243; only 3 and 1 donors, respectively, had ID50 titers above 100 against those variants.
  • A single mRNA vaccine dose boosted median Wuhan-Hu-1 ID50 titers ~1000-fold in PIDs with preexisting RBD-specific IgG, while a second dose had no effect; one dose in PIDs elicited 4.5-fold higher IgG and 7.7-fold higher IgA titers than two doses in naïve donors (NDs).
  • After one immunization in PIDs, median ID50 titers were ~3-fold lower against B.1.351, ~10-fold lower against B.1.351–Δ242-243, and 100-fold lower against SARS-CoV-1 than against Wuhan-Hu-1; neutralizing titers in PIDs after one dose were still 10-fold higher against Wuhan-Hu-1, 20-fold higher against B.1.351, 30-fold higher against B.1.351–Δ242-243, and 7-fold higher against SARS-CoV-1 than after two doses in NDs.
  • Depletion of RBD-specific antibodies from postvaccination sera abrogated neutralization of Wuhan-Hu-1, indicating that most vaccine-elicited or boosted neutralizing antibodies target the RBD.

Methods

  • Sera were collected from 15 donors with previously confirmed SARS-CoV-2 infection before and after one or two immunizations with Pfizer-BioNTech BNT162b2 or Moderna mRNA-1273, and from 13 uninfected donors after two vaccine doses; prevaccine PID samples were on average 202 days after symptom onset.
  • Neutralization was measured with pseudoviruses expressing Wuhan-Hu-1 S, B.1.351 S, B.1.351–Δ242-243 S, or SARS-CoV-1 S; binding antibodies were measured by ELISA, and memory B cell and S-specific CD4+ T cell responses were assessed from PBMCs.
  • Statistical comparisons used Wilcoxon signed rank tests for paired pre/post or variant comparisons and Wilcoxon rank sum tests between previously infected and uninfected donors.

Limitations

  • Stated: the study used a pseudovirus neutralization assay; the authors note that authentic virus and pseudovirus neutralization correlate well, but absolute sensitivity may differ, though they anticipate relative differences will not vary.
  • Stated: less-frequent B.1.351-associated mutations such as L18F, Δ244, L244H, and R246I were not examined and may further increase resistance to vaccine-elicited antibodies.
  • Evident from the text: the sample was small (15 PIDs and 13 NDs), and several experiments were performed once; correlates of protection for SARS-CoV-2 vaccines were not established.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

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Crossref · 10.1126/science.abg9175

Cites

Statistics

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Claims the paper makes

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  • Findingnone given

    Before vaccination, postinfection serum antibody neutralization responses to virus variants were variable and weak.

    “Before vaccination, postinfection serum antibody neutralization responses to virus variants were variable and weak.”
    Quote in the paperSubstantial claim
  • Findingown data

    Serum neutralization against the variant B.1.351 was enhanced by vaccination.

    “serum neutralization against the variant B.1.351 was enhanced”
    Quote in the paperSubstantial claim
  • Findingown data

    Vaccination elevated postinfection serum-neutralizing capacity approximately 1000-fold against Wuhan-Hu-1 and other strains.

    “Vaccination elevated postinfection serum-neutralizing capacity approximately 1000-fold against Wuhan-Hu-1 and other strains”
    Quote in the paperSubstantial claim
  • Findingown data

    The anti-NTD CV1 mAb was unable to neutralize either B.1.351 variant.

    “By contrast, the anti-NTD CV1 mAb was unable to neutralize either B.1.351 variant (Fig. 1D).”
    Quote in the paperNot a substantial claim
  • Findingown data

    Across all PIDs, there was a 200-fold increase in median RBD-specific IgA titers after vaccination.

    “Across all PIDs, there was a 200-fold increase in median RBD-specific IgA titers after vaccination (Fig. 2B).”
    Quote in the paperNot a substantial claim
  • May combine two claims. 23
  • Classified as probably not a substantial claim. 14
  • May combine two claims.

    Findingown data

    Although responses were relatively muted against the variant, they still showed characteristic memory responses.

    “Although responses were relatively muted against the variant, they still showed characteristic memory responses.”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingown data

    The median ID50 titers after a single immunization were ~3-fold lower against B.1.351, ~10-fold lower against B.1.351-Δ242-243, and 100-fold lower against SARS-CoV-1 than against Wuhan-Hu-1.

    “the median ID50 titers were ~3-fold lower against B.1.351, ~10-fold lower against B.1.351–Δ242-243, and 100-fold lower against SARS-CoV-1 than against Wuhan-Hu-1 (Fig. 3E).”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingown data

    As long as RBD-specific IgG+ memory B cell and antibody responses were generated during infection, a single immunization with either mRNA vaccine elicited a robust recall response that boosted the autologous neutralizing titers by ~1000-fold, and these antibody responses cross-neutralized the B.1.351 variants, but at lower titers.

    “However, as long as RBD-specific IgG+ memory B cell and antibody responses were generated during infection, a single immunization with either mRNA vaccine elicited a robust recall response that boosted the autologous neutralizing titers by ~1000-fold, and these antibody responses cross-neutralized the B.1.351 variants, but at lower titers.”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingown data

    Before vaccination, 7 of 15 sera from PIDs neutralized B.1.351-Δ242-243, and only one had titers above 100.

    “7 of 15 neutralized B.1.351–Δ242-243, and only one had titers above 100 (Fig. 3, C and E, and fig. S4).”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingown data

    The neutralizing titers elicited by a single immunization in PIDs were significantly higher than those elicited by two immunizations in NDs against all pseudoviruses tested-10-fold higher against Wuhan-Hu-1, 20-fold higher against B.1.351, 30-fold higher against B.1.351-Δ242-243, and 7-fold higher against SARS-CoV-1.

    “The neutralizing titers elicited by a single immunization in PIDs were significantly higher than those elicited by two immunizations in NDs against all pseudoviruses tested—10-fold higher against Wuhan-Hu-1 (Fig. 3A), 20-fold higher against B.1.351 (Fig. 3B), 30-fold higher against B.1.351–Δ242-243 (Fig. 3C), and 7-fold higher against SARS-CoV-1 (Fig. 3D).”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingown data

    The two PIDs that lacked RBD-specific IgG titers before immunization also lacked RBD-specific IgG+ memory B cells and had lower frequencies of S-specific IgG+ memory B cells after vaccination.

    “The two PIDs that lacked RBD-specific IgG titers before immunization (donors L and M) also lacked RBD-specific IgG+ memory B cells (Fig. 2D) and had lower frequencies of S-specific IgG+ memory B cells after vaccination.”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Findingown data

    RBD-specific IgM titers were generally lower and were not significantly boosted in response to vaccination in PIDs.

    “RBD-specific IgM titers were generally lower and were not significantly boosted in response to vaccination in PIDs (Fig. 2C).”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Findingown data

    Before vaccination, 5 of 15 sera from PIDs neutralized B.1.351, and only three had ID50 titers above 100.

    “Before vaccination, 5 of 15 sera from PIDs neutralized B.1.351, and only three had ID50 titers above 100 (Fig. 3, B and E, and fig. S4)”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingown data

    Vaccination induced an increase in the frequency of IgA+ but not IgM+ spike-specific memory B cells.

    “an increase in the frequency of IgA+ (Fig. 2F) but not IgM+ spike-specific memory B cells was observed (fig. S3).”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Findingcitation

    Sera from PIDs who experienced symptomatic SARS-CoV-2 infection and who had detectable anti-RBD IgG titers before vaccination displayed generally weak nAb titers against Wuhan-Hu-1 at 1 to 9 months after infection and lower or nonexistent titers against the B.1.351 variants.

    “Similarly, sera from PIDs who experienced symptomatic SARS-CoV-2 infection and who had detectable anti-RBD IgG titers before vaccination displayed generally weak nAb titers against Wuhan-Hu-1 at 1 to 9 months after infection and lower or nonexistent titers against the B.1.351 variants, in agreement with another study (69).”
    Quote in the paperSubstantial claim0 of 1 sources checked
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      Not checked in the free run.

  • May combine two claims.

    Findingown data

    The median half-maximal neutralizing titers (ID50) were boosted ~1000-fold after the first dose, whereas the second dose had no effect.

    “the median half-maximal neutralizing titers [half-maximal inhibitory dilution (ID50)] were boosted ~1000-fold after the first dose, whereas the second dose had no effect (Fig. 3A).”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingown data

    Only two prevaccine PID sera achieved 80% neutralization of B.1.351, and only one achieved 80% neutralization of B.1.351-Δ242-243.

    “Only two prevaccine PID sera achieved 80% neutralization of B.1.351, and only one achieved 80% neutralization of B.1.351–Δ242-243 (fig. S7A).”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingown data

    In NDs, two doses of either the Pfizer-BioNTech or Moderna vaccines elicited nAb titers against the vaccine-matched Wuhan-Hu-1, lower titers against B.1.351, and even lower titers against B.1.351-Δ242-243.

    “The above results indicate that in NDs, two doses of either the Pfizer-BioNTech or Moderna vaccines elicited nAb titers against the vaccine-matched Wuhan-Hu-1, lower titers against B.1.351, and even lower titers against B.1.351–Δ242-243.”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingown data

    Only 8 of 13 vaccinated NDs were able to achieve 80% neutralization of B.1.351-Δ242-243, and none could achieve 80% neutralization of SARS-CoV-1.

    “Only 8 of 13 vaccinated NDs were able to achieve 80% neutralization of B.1.351–Δ242-243, and none could achieve 80% neutralization of SARS-CoV-1 (fig. S7B).”
    Quote in the paperSubstantial claim
  • Classified as probably not a substantial claim.

    Premisecitation

    Neutralizing antibodies are thought to be an important component of a protective immune response against SARS-CoV-2.

    “neutralizing antibodies (nAbs) are thought to be an important component of a protective immune response against SARS-CoV-2 (14, 15).”
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      Not checked in the free run.

    • cites [17] S. J. Zost, P. Gilchuk, J. B. Case, E. Binshtein, R. E. Chen, J. P. Nkolola, A. Schäfer, J. X. Reidy, A. Trivette, R. S. Nargi, R. E. Sutton, N. Suryadevara, D. R. Martinez, L. E. Williamson, E. C. Chen, T. Jones, S. Day, L. Myers, A. O. Hassan, N. M. Kafai, E. S. Winkler, J. M. Fox, S. Shrihari, B. K. Mueller, J. Meiler, A. Chandrashekar, N. B. Mercado, J. J. Steinhardt, K. Ren, Y.-M. Loo, N. L. Kallewaard, B. T. McCune, S. P. Keeler, M. J. Holtzman, D. H. Barouch, L. E. Gralinski, R. S. Baric, L. B. Thackray, M. S. Diamond, R. H. Carnahan, J. E. Crowe Jr.,., Potently neutralizing and protect source

      Not checked in the free run.

    • cites [18] K. McMahan, J. Yu, N. B. Mercado, C. Loos, L. H. Tostanoski, A. Chandrashekar, J. Liu, L. Peter, C. Atyeo, A. Zhu, E. A. Bondzie, G. Dagotto, M. S. Gebre, C. Jacob-Dolan, Z. Li, F. Nampanya, S. Patel, L. Pessaint, A. Van Ry, K. Blade, J. Yalley-Ogunro, M. Cabus, R. Brown, A. Cook, E. Teow, H. Andersen, M. G. Lewis, D. A. Lauffenburger, G. Alter, D. H. Barouch, Correlates of protection against SARS-CoV-2 in rhesus macaques. Nature 590, 630– 634 (2021). 10.1038/s41586-020-03041-6 33276369 PMC7906955 source

      Not checked in the free run.

    • cites [19] A. Baum, D. Ajithdoss, R. Copin, A. Zhou, K. Lanza, N. Negron, M. Ni, Y. Wei, K. Mohammadi, B. Musser, G. S. Atwal, A. Oyejide, Y. Goez-Gazi, J. Dutton, E. Clemmons, H. M. Staples, C. Bartley, B. Klaffke, K. Alfson, M. Gazi, O. Gonzalez, E. Dick Jr.., R. Carrion Jr.., L. Pessaint, M. Porto, A. Cook, R. Brown, V. Ali, J. Greenhouse, T. Taylor, H. Andersen, M. G. Lewis, N. Stahl, A. J. Murphy, G. D. Yancopoulos, C. A. Kyratsous, REGN-COV2 antibodies prevent and treat SARS-CoV-2 infection in rhesus macaques and hamsters. Science 370, 1110– 1115 (2020). 10.1126/science.abe2402 33037066 PMC7857396 source

      Not checked in the free run.

    • cites [20] A. Schäfer, F. Muecksch, J. C. C. Lorenzi, S. R. Leist, M. Cipolla, S. Bournazos, F. Schmidt, R. M. Maison, A. Gazumyan, D. R. Martinez, R. S. Baric, D. F. Robbiani, T. Hatziioannou, J. V. Ravetch, P. D. Bieniasz, R. A. Bowen, M. C. Nussenzweig, T. P. Sheahan, Antibody potency, effector function, and combinations in protection and therapy for SARS-CoV-2 infection in vivo. J. Exp. Med. 218, e20201993 (2021). 10.1084/jem.20201993 33211088 PMC7673958 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    SARS-CoV-2 infection rapidly elicits nAbs that decline, but remain detectable, over several months.

    “SARS-CoV-2 infection rapidly elicits nAbs (16, 21–24) that decline, but remain detectable, over several months (25–29).”
    Quote in the paperNot a substantial claim0 of 10 sources checked
    • cites [16] T. F. Rogers, F. Zhao, D. Huang, N. Beutler, A. Burns, W. T. He, O. Limbo, C. Smith, G. Song, J. Woehl, L. Yang, R. K. Abbott, S. Callaghan, E. Garcia, J. Hurtado, M. Parren, L. Peng, S. Ramirez, J. Ricketts, M. J. Ricciardi, S. A. Rawlings, N. C. Wu, M. Yuan, D. M. Smith, D. Nemazee, J. R. Teijaro, J. E. Voss, I. A. Wilson, R. Andrabi, B. Briney, E. Landais, D. Sok, J. G. Jardine, D. R. Burton, Isolation of potent SARS-CoV-2 neutralizing antibodies and protection from disease in a small animal model. Science 369, 956– 963 (2020). 10.1126/science.abc7520 32540903 PMC7299280 source

      Not checked in the free run.

    • cites [21] M. S. Suthar, M. G. Zimmerman, R. C. Kauffman, G. Mantus, S. L. Linderman, W. H. Hudson, A. Vanderheiden, L. Nyhoff, C. W. Davis, O. Adekunle, M. Affer, M. Sherman, S. Reynolds, H. P. Verkerke, D. N. Alter, J. Guarner, J. Bryksin, M. C. Horwath, C. M. Arthur, N. Saakadze, G. H. Smith, S. Edupuganti, E. M. Scherer, K. Hellmeister, A. Cheng, J. A. Morales, A. S. Neish, S. R. Stowell, F. Frank, E. Ortlund, E. J. Anderson, V. D. Menachery, N. Rouphael, A. K. Mehta, D. S. Stephens, R. Ahmed, J. D. Roback, J. Wrammert, Rapid Generation of Neutralizing Antibody Responses in COVID-19 Patients. Cell Re source

      Not checked in the free run.

    • cites [22] E. Seydoux, L. J. Homad, A. J. MacCamy, K. R. Parks, N. K. Hurlburt, M. F. Jennewein, N. R. Akins, A. B. Stuart, Y.-H. Wan, J. Feng, R. E. Whaley, S. Singh, M. Boeckh, K. W. Cohen, M. J. McElrath, J. A. Englund, H. Y. Chu, M. Pancera, A. T. McGuire, L. Stamatatos, Analysis of a SARS-CoV-2-Infected Individual Reveals Development of Potent Neutralizing Antibodies with Limited Somatic Mutation. Immunity 53, 98– 105.e5 (2020). 10.1016/j.immuni.2020.06.001 32561270 PMC7276322 source

      Not checked in the free run.

    • cites [23] D. F. Robbiani, C. Gaebler, F. Muecksch, J. C. C. Lorenzi, Z. Wang, A. Cho, M. Agudelo, C. O. Barnes, A. Gazumyan, S. Finkin, T. Hägglöf, T. Y. Oliveira, C. Viant, A. Hurley, H.-H. Hoffmann, K. G. Millard, R. G. Kost, M. Cipolla, K. Gordon, F. Bianchini, S. T. Chen, V. Ramos, R. Patel, J. Dizon, I. Shimeliovich, P. Mendoza, H. Hartweger, L. Nogueira, M. Pack, J. Horowitz, F. Schmidt, Y. Weisblum, E. Michailidis, A. W. Ashbrook, E. Waltari, J. E. Pak, K. E. Huey-Tubman, N. Koranda, P. R. Hoffman, A. P. West Jr.., C. M. Rice, T. Hatziioannou, P. J. Bjorkman, P. D. Bieniasz, M. Caskey, M. C. Nuss source

      Not checked in the free run.

    • cites [24] P. J. M. Brouwer, T. G. Caniels, K. van der Straten, J. L. Snitselaar, Y. Aldon, S. Bangaru, J. L. Torres, N. M. A. Okba, M. Claireaux, G. Kerster, A. E. H. Bentlage, M. M. van Haaren, D. Guerra, J. A. Burger, E. E. Schermer, K. D. Verheul, N. van der Velde, A. van der Kooi, J. van Schooten, M. J. van Breemen, T. P. L. Bijl, K. Sliepen, A. Aartse, R. Derking, I. Bontjer, N. A. Kootstra, W. J. Wiersinga, G. Vidarsson, B. L. Haagmans, A. B. Ward, G. J. de Bree, R. W. Sanders, M. J. van Gils, Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability. Science 3 source

      Not checked in the free run.

    • cites [25] J. M. Dan, J. Mateus, Y. Kato, K. M. Hastie, E. D. Yu, C. E. Faliti, A. Grifoni, S. I. Ramirez, S. Haupt, A. Frazier, C. Nakao, V. Rayaprolu, S. A. Rawlings, B. Peters, F. Krammer, V. Simon, E. O. Saphire, D. M. Smith, D. Weiskopf, A. Sette, S. Crotty, Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection. Science 371, eabf4063 (2021). 10.1126/science.abf4063 33408181 PMC7919858 source

      Not checked in the free run.

    • cites [26] L. B. Rodda, J. Netland, L. Shehata, K. B. Pruner, P. A. Morawski, C. D. Thouvenel, K. K. Takehara, J. Eggenberger, E. A. Hemann, H. R. Waterman, M. L. Fahning, Y. Chen, M. Hale, J. Rathe, C. Stokes, S. Wrenn, B. Fiala, L. Carter, J. A. Hamerman, N. P. King, M. Gale Jr.., D. J. Campbell, D. J. Rawlings, M. Pepper, Functional SARS-CoV-2-Specific Immune Memory Persists after Mild COVID-19. Cell 184, 169– 183.e17 (2021). 10.1016/j.cell.2020.11.029 33296701 PMC7682481 source

      Not checked in the free run.

    • cites [27] C. Gaebler, Z. Wang, J. C. C. Lorenzi, F. Muecksch, S. Finkin, M. Tokuyama, A. Cho, M. Jankovic, D. Schaefer-Babajew, T. Y. Oliveira, M. Cipolla, C. Viant, C. O. Barnes, Y. Bram, G. Breton, T. Hägglöf, P. Mendoza, A. Hurley, M. Turroja, K. Gordon, K. G. Millard, V. Ramos, F. Schmidt, Y. Weisblum, D. Jha, M. Tankelevich, G. Martinez-Delgado, J. Yee, R. Patel, J. Dizon, C. Unson-O’Brien, I. Shimeliovich, D. F. Robbiani, Z. Zhao, A. Gazumyan, R. E. Schwartz, T. Hatziioannou, P. J. Bjorkman, S. Mehandru, P. D. Bieniasz, M. Caskey, M. C. Nussenzweig, Evolution of antibody immunity to SARS-CoV-2. Na source

      Not checked in the free run.

    • cites [28] J. Seow, C. Graham, B. Merrick, S. Acors, S. Pickering, K. J. A. Steel, O. Hemmings, A. O’Byrne, N. Kouphou, R. P. Galao, G. Betancor, H. D. Wilson, A. W. Signell, H. Winstone, C. Kerridge, I. Huettner, J. M. Jimenez-Guardeño, M. J. Lista, N. Temperton, L. B. Snell, K. Bisnauthsing, A. Moore, A. Green, L. Martinez, B. Stokes, J. Honey, A. Izquierdo-Barras, G. Arbane, A. Patel, M. K. I. Tan, L. O’Connell, G. O’Hara, E. MacMahon, S. Douthwaite, G. Nebbia, R. Batra, R. Martinez-Nunez, M. Shankar-Hari, J. D. Edgeworth, S. J. D. Neil, M. H. Malim, K. J. Doores, Longitudinal observation and decline source

      Not checked in the free run.

    • cites [29] F. Muecksch, H. Wise, B. Batchelor, M. Squires, E. Semple, C. Richardson, J. McGuire, S. Clearly, E. Furrie, N. Greig, G. Hay, K. Templeton, J. C. C. Lorenzi, T. Hatziioannou, S. Jenks, P. D. Bieniasz, Longitudinal Serological Analysis and Neutralizing Antibody Levels in Coronavirus Disease 2019 Convalescent Patients. J. Infect. Dis. 223, 389– 398 (2021). 10.1093/infdis/jiaa659 33140086 PMC7665595 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Numerous neutralizing anti-RBD monoclonal antibodies have been characterized, the most potent of which block the RBD-ACE2 interaction.

    “Numerous neutralizing anti-RBD monoclonal antibodies (mAbs) have been characterized, the most potent of which block the RBD-ACE2 interaction (16, 17, 22–24, 32–37).”
    Quote in the paperNot a substantial claim0 of 10 sources checked
    • cites [16] T. F. Rogers, F. Zhao, D. Huang, N. Beutler, A. Burns, W. T. He, O. Limbo, C. Smith, G. Song, J. Woehl, L. Yang, R. K. Abbott, S. Callaghan, E. Garcia, J. Hurtado, M. Parren, L. Peng, S. Ramirez, J. Ricketts, M. J. Ricciardi, S. A. Rawlings, N. C. Wu, M. Yuan, D. M. Smith, D. Nemazee, J. R. Teijaro, J. E. Voss, I. A. Wilson, R. Andrabi, B. Briney, E. Landais, D. Sok, J. G. Jardine, D. R. Burton, Isolation of potent SARS-CoV-2 neutralizing antibodies and protection from disease in a small animal model. Science 369, 956– 963 (2020). 10.1126/science.abc7520 32540903 PMC7299280 source

      Not checked in the free run.

    • cites [17] S. J. Zost, P. Gilchuk, J. B. Case, E. Binshtein, R. E. Chen, J. P. Nkolola, A. Schäfer, J. X. Reidy, A. Trivette, R. S. Nargi, R. E. Sutton, N. Suryadevara, D. R. Martinez, L. E. Williamson, E. C. Chen, T. Jones, S. Day, L. Myers, A. O. Hassan, N. M. Kafai, E. S. Winkler, J. M. Fox, S. Shrihari, B. K. Mueller, J. Meiler, A. Chandrashekar, N. B. Mercado, J. J. Steinhardt, K. Ren, Y.-M. Loo, N. L. Kallewaard, B. T. McCune, S. P. Keeler, M. J. Holtzman, D. H. Barouch, L. E. Gralinski, R. S. Baric, L. B. Thackray, M. S. Diamond, R. H. Carnahan, J. E. Crowe Jr.,., Potently neutralizing and protect source

      Not checked in the free run.

    • cites [22] E. Seydoux, L. J. Homad, A. J. MacCamy, K. R. Parks, N. K. Hurlburt, M. F. Jennewein, N. R. Akins, A. B. Stuart, Y.-H. Wan, J. Feng, R. E. Whaley, S. Singh, M. Boeckh, K. W. Cohen, M. J. McElrath, J. A. Englund, H. Y. Chu, M. Pancera, A. T. McGuire, L. Stamatatos, Analysis of a SARS-CoV-2-Infected Individual Reveals Development of Potent Neutralizing Antibodies with Limited Somatic Mutation. Immunity 53, 98– 105.e5 (2020). 10.1016/j.immuni.2020.06.001 32561270 PMC7276322 source

      Not checked in the free run.

    • cites [23] D. F. Robbiani, C. Gaebler, F. Muecksch, J. C. C. Lorenzi, Z. Wang, A. Cho, M. Agudelo, C. O. Barnes, A. Gazumyan, S. Finkin, T. Hägglöf, T. Y. Oliveira, C. Viant, A. Hurley, H.-H. Hoffmann, K. G. Millard, R. G. Kost, M. Cipolla, K. Gordon, F. Bianchini, S. T. Chen, V. Ramos, R. Patel, J. Dizon, I. Shimeliovich, P. Mendoza, H. Hartweger, L. Nogueira, M. Pack, J. Horowitz, F. Schmidt, Y. Weisblum, E. Michailidis, A. W. Ashbrook, E. Waltari, J. E. Pak, K. E. Huey-Tubman, N. Koranda, P. R. Hoffman, A. P. West Jr.., C. M. Rice, T. Hatziioannou, P. J. Bjorkman, P. D. Bieniasz, M. Caskey, M. C. Nuss source

      Not checked in the free run.

    • cites [24] P. J. M. Brouwer, T. G. Caniels, K. van der Straten, J. L. Snitselaar, Y. Aldon, S. Bangaru, J. L. Torres, N. M. A. Okba, M. Claireaux, G. Kerster, A. E. H. Bentlage, M. M. van Haaren, D. Guerra, J. A. Burger, E. E. Schermer, K. D. Verheul, N. van der Velde, A. van der Kooi, J. van Schooten, M. J. van Breemen, T. P. L. Bijl, K. Sliepen, A. Aartse, R. Derking, I. Bontjer, N. A. Kootstra, W. J. Wiersinga, G. Vidarsson, B. L. Haagmans, A. B. Ward, G. J. de Bree, R. W. Sanders, M. J. van Gils, Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability. Science 3 source

      Not checked in the free run.

    • cites [32] C. O. Barnes, A. P. West Jr., K. E. Huey-Tubman, M. A. G. Hoffmann, N. G. Sharaf, P. R. Hoffman, N. Koranda, H. B. Gristick, C. Gaebler, F. Muecksch, J. C. Cetrulo Lorenzi, S. Finkin, T. Hägglöf, A. Hurley, K. G. Millard, Y. Weisblum, F. Schmidt, T. Hatziioannou, P. D. Bieniasz, M. Caskey, D. F. Robbiani, M. C. Nussenzweig, P. J. Bjorkman, Structures of Human Antibodies Bound to SARS-CoV-2 Spike Reveal Common Epitopes and Recurrent Features of Antibodies. Cell 182, 828– 842.e16 (2020). 10.1016/j.cell.2020.06.025 32645326 PMC7311918 source

      Not checked in the free run.

    • cites [33] L. Liu, P. Wang, M. S. Nair, J. Yu, M. Rapp, Q. Wang, Y. Luo, J. F.-W. Chan, V. Sahi, A. Figueroa, X. V. Guo, G. Cerutti, J. Bimela, J. Gorman, T. Zhou, Z. Chen, K.-Y. Yuen, P. D. Kwong, J. G. Sodroski, M. T. Yin, Z. Sheng, Y. Huang, L. Shapiro, D. D. Ho, Potent neutralizing antibodies against multiple epitopes on SARS-CoV-2 spike. Nature 584, 450– 456 (2020). 10.1038/s41586-020-2571-7 32698192 source

      Not checked in the free run.

    • cites [34] J. Hansen, A. Baum, K. E. Pascal, V. Russo, S. Giordano, E. Wloga, B. O. Fulton, Y. Yan, K. Koon, K. Patel, K. M. Chung, A. Hermann, E. Ullman, J. Cruz, A. Rafique, T. Huang, J. Fairhurst, C. Libertiny, M. Malbec, W. Y. Lee, R. Welsh, G. Farr, S. Pennington, D. Deshpande, J. Cheng, A. Watty, P. Bouffard, R. Babb, N. Levenkova, C. Chen, B. Zhang, A. Romero Hernandez, K. Saotome, Y. Zhou, M. Franklin, S. Sivapalasingam, D. C. Lye, S. Weston, J. Logue, R. Haupt, M. Frieman, G. Chen, W. Olson, A. J. Murphy, N. Stahl, G. D. Yancopoulos, C. A. Kyratsous, Studies in humanized mice and convalescent hu source

      Not checked in the free run.

    • cites [35] B. Ju, Q. Zhang, J. Ge, R. Wang, J. Sun, X. Ge, J. Yu, S. Shan, B. Zhou, S. Song, X. Tang, J. Yu, J. Lan, J. Yuan, H. Wang, J. Zhao, S. Zhang, Y. Wang, X. Shi, L. Liu, J. Zhao, X. Wang, Z. Zhang, L. Zhang, Human neutralizing antibodies elicited by SARS-CoV-2 infection. Nature 584, 115– 119 (2020). 10.1038/s41586-020-2380-z 32454513 source

      Not checked in the free run.

    • cites [36] Y. Cao, B. Su, X. Guo, W. Sun, Y. Deng, L. Bao, Q. Zhu, X. Zhang, Y. Zheng, C. Geng, X. Chai, R. He, X. Li, Q. Lv, H. Zhu, W. Deng, Y. Xu, Y. Wang, L. Qiao, Y. Tan, L. Song, G. Wang, X. Du, N. Gao, J. Liu, J. Xiao, X. D. Su, Z. Du, Y. Feng, C. Qin, C. Qin, R. Jin, X. S. Xie, Potent Neutralizing Antibodies against SARS-CoV-2 Identified by High-Throughput Single-Cell Sequencing of Convalescent Patients’ B Cells. Cell 182, 73– 84.e16 (2020). 10.1016/j.cell.2020.05.025 32425270 PMC7231725 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Most serum nAb responses elicited during natural infection are directed at the RBD.

    “Most serum nAb responses elicited during natural infection are directed at the RBD (21, 23, 30, 31).”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [21] M. S. Suthar, M. G. Zimmerman, R. C. Kauffman, G. Mantus, S. L. Linderman, W. H. Hudson, A. Vanderheiden, L. Nyhoff, C. W. Davis, O. Adekunle, M. Affer, M. Sherman, S. Reynolds, H. P. Verkerke, D. N. Alter, J. Guarner, J. Bryksin, M. C. Horwath, C. M. Arthur, N. Saakadze, G. H. Smith, S. Edupuganti, E. M. Scherer, K. Hellmeister, A. Cheng, J. A. Morales, A. S. Neish, S. R. Stowell, F. Frank, E. Ortlund, E. J. Anderson, V. D. Menachery, N. Rouphael, A. K. Mehta, D. S. Stephens, R. Ahmed, J. D. Roback, J. Wrammert, Rapid Generation of Neutralizing Antibody Responses in COVID-19 Patients. Cell Re source

      Not checked in the free run.

    • cites [23] D. F. Robbiani, C. Gaebler, F. Muecksch, J. C. C. Lorenzi, Z. Wang, A. Cho, M. Agudelo, C. O. Barnes, A. Gazumyan, S. Finkin, T. Hägglöf, T. Y. Oliveira, C. Viant, A. Hurley, H.-H. Hoffmann, K. G. Millard, R. G. Kost, M. Cipolla, K. Gordon, F. Bianchini, S. T. Chen, V. Ramos, R. Patel, J. Dizon, I. Shimeliovich, P. Mendoza, H. Hartweger, L. Nogueira, M. Pack, J. Horowitz, F. Schmidt, Y. Weisblum, E. Michailidis, A. W. Ashbrook, E. Waltari, J. E. Pak, K. E. Huey-Tubman, N. Koranda, P. R. Hoffman, A. P. West Jr.., C. M. Rice, T. Hatziioannou, P. J. Bjorkman, P. D. Bieniasz, M. Caskey, M. C. Nuss source

      Not checked in the free run.

    • cites [30] L. Piccoli, Y.-J. Park, M. A. Tortorici, N. Czudnochowski, A. C. Walls, M. Beltramello, C. Silacci-Fregni, D. Pinto, L. E. Rosen, J. E. Bowen, O. J. Acton, S. Jaconi, B. Guarino, A. Minola, F. Zatta, N. Sprugasci, J. Bassi, A. Peter, A. De Marco, J. C. Nix, F. Mele, S. Jovic, B. F. Rodriguez, S. V. Gupta, F. Jin, G. Piumatti, G. Lo Presti, A. F. Pellanda, M. Biggiogero, M. Tarkowski, M. S. Pizzuto, E. Cameroni, C. Havenar-Daughton, M. Smithey, D. Hong, V. Lepori, E. Albanese, A. Ceschi, E. Bernasconi, L. Elzi, P. Ferrari, C. Garzoni, A. Riva, G. Snell, F. Sallusto, K. Fink, H. W. Virgin, A. La source

      Not checked in the free run.

    • cites [31] T. L. Steffen, E. T. Stone, M. Hassert, E. Geerling, B. T. Grimberg, A. M. Espino, P. Pantoja, C. Climent, D. F. Hoft, S. L. George, C. A. Sariol, A. K. Pinto, J. D. Brien, The receptor binding domain of SARS-CoV-2 spike is the key target of neutralizing antibody in human polyclonal sera. bioRxiv 2020.08.21.261727 [Preprint]. 22 August 2020. 10.1101/2020.08.21.261727. 10.1101/2020.08.21.261727 source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Recently, viral variants of concern have emerged in the UK (B.1.1.7), South Africa (B.1.351), and Brazil (P.1) that harbor specific mutations in their S proteins that may be associated with increased transmissibility.

    “Recently, viral variants of concern have emerged in the UK (B.1.1.7), South Africa (B.1.351), and Brazil (P.1) that harbor specific mutations in their S proteins that may be associated with increased transmissibility (50–55).”
    Quote in the paperSubstantial claim0 of 6 sources checked
    • cites [50] A. Rambaut, N. Loman, O. Pybus, W. Barclay, J. Barrett, A. Carabelli, T. Connor, T. Peacock, D. L. Robertson, E. Volz, COVID-19 Genomics Consortium UK (CoG-UK), “Preliminary genomic characterisation of an emergent SARS-CoV-2 lineage in the UK defined by a novel set of spike mutations” (Virological, 2021); https://virological.org/t/preliminary-genomic-characterisation-of-an-emergent-sars-cov-2-lineage-in-the-uk-defined-by-a-novel-set-of-spike-mutations/563.

      Not checked in the free run.

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      Not checked in the free run.

    • cites [52] H. Tegally, E. Wilkinson, M. Giovanetti, A. Iranzadeh, V. Fonseca, J. Giandhari, D. Doolabh, S. Pillay, E. J. San, N. Msomi, K. Mlisana, A. von Gottberg, S. Walaza, M. Allam, A. Ismail, T. Mohale, A. J. Glass, S. Engelbrecht, G. Van Zyl, W. Preiser, F. Petruccione, A. Sigal, D. Hardie, G. Marais, M. Hsiao, S. Korsman, M.-A. Davies, L. Tyers, I. Mudau, D. York, C. Maslo, D. Goedhals, S. Abrahams, O. Laguda-Akingba, A. Alisoltani-Dehkordi, A. Godzik, C. K. Wibmer, B. T. Sewell, J. Lourenço, L. C. J. Alcantara, S. L. Kosakovsky Pond, S. Weaver, D. Martin, R. J. Lessells, J. N. Bhiman, C. Williams source

      Not checked in the free run.

    • cites [53] N. G. Davies, S. Abbott, R. C. Barnard, C. I. Jarvis, A. J. Kucharski, J. D. Munday, C. A. B. Pearson, T. W. Russell, D. C. Tully, A. D. Washburne, T. Wenseleers, A. Gimma, W. Waites, K. L. M. Wong, K. van Zandvoort, J. D. Silverman, CMMID COVID-19 Working Group, The COVID-19 Genomics UK (COG-UK) Consortium, K. Diaz-Ordaz, R. Keogh, R. M. Eggo, S. Funk, M. Jit, K. E. Atkins, W. J. Edmunds, Estimated transmissibility and impact of SARS-CoV-2 lineage B.1.1.7 in England. Science 372, eabg3055 (2021). 10.1126/science.abg3055 33658326 PMC8128288 source

      Not checked in the free run.

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      Not checked in the free run.

    • cites [55] N. R. Faria, I. Morales Claro, D. Candido, L. A. Moyses Franco, P. S. Andrade, T. M. Coletti, C. A. M. Silva, F. C. Sales, E. R. Manuli, R. S. Aguiar, N. Gaburo, C. d. C. Camilo, N. A. Fraiji, M. A. Esashika Crispim, M. d. P. S. S. Carvalho, A. Rambaut, N. Loman, O. G. Pybus, E. C. Sabino, CADDE Genomic Network, “Genomic characterisation of an emergent SARS-CoV-2 lineage in Manaus: preliminary findings” (Virological, 2021); https://virological.org/t/genomic-characterisation-of-an-emergent-sars-cov-2-lineage-in-manaus-preliminary-findings/586.

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Two mRNA-based vaccines (Pfizer-BioNTech BNT162b2 and Moderna mRNA-1273) encode a stabilized ectodomain version of the S protein derived from the Wuhan-Hu-1 variant isolated in December 2019.

    “Both vaccines encode a stabilized ectodomain version of the S protein derived from the Wuhan-Hu-1 variant isolated in December 2019 (43)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [43] F. Wu, S. Zhao, B. Yu, Y.-M. Chen, W. Wang, Z.-G. Song, Y. Hu, Z.-W. Tao, J.-H. Tian, Y.-Y. Pei, M.-L. Yuan, Y.-L. Zhang, F.-H. Dai, Y. Liu, Q.-M. Wang, J.-J. Zheng, L. Xu, E. C. Holmes, Y.-Z. Zhang, A new coronavirus associated with human respiratory disease in China. Nature 579, 265– 269 (2020). 10.1038/s41586-020-2008-3 32015508 PMC7094943 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Reduced sensitivity to vaccine-elicited nAbs has been reported for other B.1.351 variants.

    “Reduced sensitivity to vaccine-elicited nAbs has been reported for other B.1.351 variants (66, 83, 84).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [66] P. Wang, M. S. Nair, L. Liu, S. Iketani, Y. Luo, Y. Guo, M. Wang, J. Yu, B. Zhang, P. D. Kwong, B. S. Graham, J. R. Mascola, J. Y. Chang, M. T. Yin, M. Sobieszczyk, C. A. Kyratsous, L. Shapiro, Z. Sheng, Y. Huang, D. D. Ho, Antibody Resistance of SARS-CoV-2 Variants B.1.351 and B.1.1.7. bioRxiv 2021.01.25.428137 [Preprint]. 12 February 2021. 10.1101/2021.01.25.428137. 10.1101/2021.01.25.428137 33684923 source

      Not checked in the free run.

    • cites [83] Y. Liu, J. Liu, H. Xia, X. Zhang, C. R. Fontes-Garfias, K. A. Swanson, H. Cai, R. Sarkar, W. Chen, M. Cutler, D. Cooper, S. C. Weaver, A. Muik, U. Sahin, K. U. Jansen, X. Xie, P. R. Dormitzer, P.-Y. Shi, Neutralizing Activity of BNT162b2-Elicited Serum. N. Engl. J. Med. 384, 1466– 1468 (2021). 10.1056/NEJMc2102017 33684280 PMC7944950 source

      Not checked in the free run.

    • cites [84] K. Wu, A. P. Werner, M. Koch, A. Choi, E. Narayanan, G. B. E. Stewart-Jones, T. Colpitts, H. Bennett, S. Boyoglu-Barnum, W. Shi, J. I. Moliva, N. J. Sullivan, B. S. Graham, A. Carfi, K. S. Corbett, R. A. Seder, D. K. Edwards, Serum Neutralizing Activity Elicited by mRNA-1273 Vaccine. N. Engl. J. Med. 384, 1468– 1470 (2021). 10.1056/NEJMc2102179 33730471 PMC8008744 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The B.1.351 lineage is defined by the D80A and D215G mutations in the NTD; the K417N, E484K, and N501Y mutations in the RBD; and the D614G mutation in S1.

    “the B.1.351 lineage, which is defined by the D80A (amino acid substitution from aspartic acid to alanine at position 80) and D215G mutations in the NTD; the K417N, E484K, and N501Y mutations in the RBD; and the D614G mutation in S1 (52, 56).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [52] H. Tegally, E. Wilkinson, M. Giovanetti, A. Iranzadeh, V. Fonseca, J. Giandhari, D. Doolabh, S. Pillay, E. J. San, N. Msomi, K. Mlisana, A. von Gottberg, S. Walaza, M. Allam, A. Ismail, T. Mohale, A. J. Glass, S. Engelbrecht, G. Van Zyl, W. Preiser, F. Petruccione, A. Sigal, D. Hardie, G. Marais, M. Hsiao, S. Korsman, M.-A. Davies, L. Tyers, I. Mudau, D. York, C. Maslo, D. Goedhals, S. Abrahams, O. Laguda-Akingba, A. Alisoltani-Dehkordi, A. Godzik, C. K. Wibmer, B. T. Sewell, J. Lourenço, L. C. J. Alcantara, S. L. Kosakovsky Pond, S. Weaver, D. Martin, R. J. Lessells, J. N. Bhiman, C. Williams source

      Not checked in the free run.

    • cites [56] Á. O’Toole, V. Hill, O. G. Pybus, A. Watts, I. I. Bogoch, K. Khan, J. P. Messina, The COVID-19 Genomics UK (COG-UK) consortium, Network for Genomic Surveillance in South Africa (NGS-SA), Brazil-UK CADDE Genomic Network, H. Tegally, R. R. Lessells, J. Giandhari, S. Pillay, K. A. Tumedi, G. Nyepetsi, M. Kebabonye, M. Matsheka, M. Mine, S. Tokajian, H. Hassan, T. Salloum, G. Merhi, J. Koweyes, J. L. Geoghegan, J. de Ligt, X. Ren, M. Storey, N. E. Freed, C. Pattabiraman, P. Prasad, A. S. Desai, R. Vasanthapuram, T. F. Schulz, L. Steinbrück, T. Stadler, Swiss Viollier Sequencing Consortium, A. Pari source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    The two mRNA vaccines that are based on the Wuhan-Hu-1 variant can elicit and/or boost nAb responses but their potency is reduced against divergent variants.

    “Collectively, our data suggest that the two mRNA vaccines that are based on the Wuhan-Hu-1 variant can elicit and/or boost nAb responses but that their potency is reduced against divergent variants.”
    Quote in the paperSubstantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    An A701V mutation in S2 is also observed at high frequencies in B.1.351, whereas deletions in residues 242 to 244 as well as R246I and L18F mutations in the NTD are present at lower frequencies.

    “An A701V mutation in S2 is also observed at high frequencies, whereas deletions in residues 242 to 244 as well as R246I and L18F mutations in the NTD are present at lower frequencies (52).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [52] H. Tegally, E. Wilkinson, M. Giovanetti, A. Iranzadeh, V. Fonseca, J. Giandhari, D. Doolabh, S. Pillay, E. J. San, N. Msomi, K. Mlisana, A. von Gottberg, S. Walaza, M. Allam, A. Ismail, T. Mohale, A. J. Glass, S. Engelbrecht, G. Van Zyl, W. Preiser, F. Petruccione, A. Sigal, D. Hardie, G. Marais, M. Hsiao, S. Korsman, M.-A. Davies, L. Tyers, I. Mudau, D. York, C. Maslo, D. Goedhals, S. Abrahams, O. Laguda-Akingba, A. Alisoltani-Dehkordi, A. Godzik, C. K. Wibmer, B. T. Sewell, J. Lourenço, L. C. J. Alcantara, S. L. Kosakovsky Pond, S. Weaver, D. Martin, R. J. Lessells, J. N. Bhiman, C. Williams source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The B.1.1.7, B.1.351, and P.1 lineages all harbor a N501Y mutation in the RBD, which increases the affinity for the ACE2 receptor, and a D614G mutation, which increases virion spike density, infectivity, and transmissibility.

    “The B.1.1.7, B.1.351, and P.1 lineages all harbor a N501Y mutation in the RBD, which increases the affinity for the ACE2 receptor (57, 58), and a D614G mutation, which increases virion spike density, infectivity, and transmissibility (59, 60).”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [57] K. K. Chan, T. J. C. Tan, K. K. Narayanan, E. Procko, An engineered decoy receptor for SARS-CoV-2 broadly binds protein S sequence variants. Sci. Adv. 7, eabf1738 (2021). 10.1126/sciadv.abf1738 33597251 PMC7888922 source

      Not checked in the free run.

    • cites [58] T. N. Starr, A. J. Greaney, A. Addetia, W. W. Hannon, M. C. Choudhary, A. S. Dingens, J. Z. Li, J. D. Bloom, Prospective mapping of viral mutations that escape antibodies used to treat COVID-19. Science 371, 850– 854 (2021). 10.1126/science.abf9302 33495308 PMC7963219 source

      Not checked in the free run.

    • cites [59] L. Zhang, C. B. Jackson, H. Mou, A. Ojha, H. Peng, B. D. Quinlan, E. S. Rangarajan, A. Pan, A. Vanderheiden, M. S. Suthar, W. Li, T. Izard, C. Rader, M. Farzan, H. Choe, SARS-CoV-2 spike-protein D614G mutation increases virion spike density and infectivity. Nat. Commun. 11, 6013 (2020). 10.1038/s41467-020-19808-4 33243994 PMC7693302 source

      Not checked in the free run.

    • cites [60] B. Zhou, T. Thi Nhu Thao, D. Hoffmann, A. Taddeo, N. Ebert, F. Labroussaa, A. Pohlmann, J. King, S. Steiner, J. N. Kelly, J. Portmann, N. J. Halwe, L. Ulrich, B. S. Trüeb, X. Fan, B. Hoffmann, L. Wang, L. Thomann, X. Lin, H. Stalder, B. Pozzi, S. de Brot, N. Jiang, D. Cui, J. Hossain, M. Wilson, M. Keller, T. J. Stark, J. R. Barnes, R. Dijkman, J. Jores, C. Benarafa, D. E. Wentworth, V. Thiel, M. Beer, SARS-CoV-2 spike D614G change enhances replication and transmission. Nature 592, 122– 127 (2021). 10.1038/s41586-021-03361-1 33636719 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Experiments were performed once.

    “Experiments were performed once.”
    Quote in the paperNot a substantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Data are representative of two independent experiments.

    “Data are representative of two independent experiments.”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Interpretationown data

    Most previously infected subjects will benefit from a single immunization with either the Pfizer-BioNTech or Moderna vaccines, as it will lead to significant increases in serum nAb responses against vaccine-matched and emerging variants.

    “Our study suggests that most previously infected subjects will benefit from a single immunization with either the Pfizer-BioNTech or Moderna vaccines, as it will lead to significant increases in serum nAb responses against vaccine-matched and emerging variants.”
    Quote in the paperSubstantial claim
  • Classified as probably not a substantial claim.

    Study design and conductown data

    The viral stocks were appropriately diluted to achieve comparable entry levels during the neutralization experiments.

    “The viral stocks were appropriately diluted to achieve comparable entry levels during the neutralization experiments (fig. S1).”
    Quote in the paperSubstantial claim
33 of 33
  • The paper relies on this without support.

    Correlates of protection in humans against repeat infection or after vaccination have not been firmly established.

    “Although the correlates of protection in humans against repeat infection or after vaccination have not been firmly established”
  • The paper relies on this without support.

    Correlates of protection for SARS-CoV-2 vaccines have not been established.

    “Although the correlates of protection for SARS-CoV-2 vaccines have not been established”
2 of 2

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • mRNA vaccines induced robust circulating antibody responses to SARS-CoV-2 spike protein and spike RBD, with distinct early response patterns in naïve and recovered individuals.

    “As reported previously by our group and others, mRNA vaccines induced robust circulating antibody responses to the SARS-CoV-2 spike protein and spike RBD with distinct patterns of early response in SARS-CoV-2–naïve and –recovered individuals (Fig. 1B) (16, 34–36).”
  • Vaccination of convalescent individuals led to 2-10-fold higher neutralisation titres than naive individuals after primary vaccination.

    “Aggregating these studies, we found that vaccination of convalescent individuals led to 2–10-fold higher neutralisation titres than that seen in naive individuals after primary vaccination (figure 3 ; appendix p 19)26, 27, 28, 29, 30, 31”
  • Vaccination with a single dose of mRNA vaccine is sufficient to boost neutralising antibody responses in previously infected individuals, and a second dose has minimal additional effect.

    “These studies have found that vaccination with a single dose of mRNA vaccine is sufficient to boost responses in previously infected individuals (and indeed a second dose has minimal effect).28, 29”
  • Vaccination of convalescent individuals improved cross-reactivity to variants.

    “and improved cross-reactivity to variants.27, 28, 29, 30”
  • A preliminary analysis of reinfection trends in England suggested that the Delta variant may have a higher risk of reinfection compared to the Alpha variant, but this analysis did not take into account the temporal trend in the population at risk for reinfection, which may have biased the findings.

    “A preliminary analysis of reinfection trends in England suggested that the Delta variant may have a higher risk of reinfection compared to the Alpha variant ( 20 ); however, this analysis did not take into account the temporal trend in the population at risk for reinfection, which may have biased the findings.”

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Figure 4 panel references do not match the assays described

    Minor

    The text cites panel C as evidence of RBD-antibody removal and panel D as evidence that anti-S2P antibodies were retained. The figure caption instead identifies C as a neutralization assay and D as an RBD-binding assay; the S2P-binding assay for those donors is panel E.

1 of 1

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References 94 · Cited by 557

Authors
Stamatatos, L., Czartoski, J., Wan, Y.-H., Homad, L. J., Rubin, V., Glantz, H., Neradilek, M., Seydoux, E., Jennewein, M. F., MacCamy, A. J., Feng, J., Mize, G., De Rosa, S. C., Finzi, A., Lemos, M. P., Cohen, K. W., Moodie, Z., McElrath, M. J., & McGuire, A. T.
Affiliations
  • University of Washington (US)
  • Fred Hutch Cancer Center (US)
  • Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
  • Centre Hospitalier de l’Université de Montréal (CA)
Corresponding author
  • Stamatatos, Leonidas
  • McElrath, M. Juliana
  • McGuire, Andrew T.
Venue
Science
Published
2021-06-25
Volume
372
Issue
6549
Pages
1413-1418
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W3136570200
Cited by
557
References
94
Citations by year
2026: 14 · 2025: 35 · 2024: 49 · 2023: 72 · 2022: 211 · 2021: 175
FWCI
40.11
Type
journal article
Language
en
Open access
Locations
  • Science (publishedVersion, cc-by)
  • medRxiv (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion, cc-by-nc-nd)
Funders
  • National Institute of Allergy and Infectious Diseases (UM1 AI068618-14S1, 2UM1AI069481-15, UM1A057266-S1)
  • Paul G. Allen Family Foundation
  • Fred Hutchinson Cancer Research Center
  • Joel D. Meyers Endowed Chair
Topics
  • Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
  • Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
Keywords
mRNA vaccines, SARS-CoV-2, booster vaccination, B.1.351 variant, reinfection protection, memory B cells, antibody neutralization

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-06.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-06.

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