Durability of mRNA-1273 vaccine–induced antibodies against SARS-CoV-2 variants
Open accessAbstract
A boost for boosters: The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern poses a potential obstacle to achieving vaccine-induced immunity. Pegu et al . examined how viral variants, including the B.1.351 (Beta) and B.1.617.2 (Delta) variant, affected the immune response in a small number of individuals who received the Moderna mRNA-1273 vaccine. By analyzing sera obtained 6 months after the second shot in the primary vaccine series, the researchers found that neutralizing antibody titers persisted against all variants tested. However, neutralizing antibodies against the B1.351 variant had dropped considerably by 6 months, and some individuals had weak, and in some cases no, neutralizing activity. These data may help to guide public health policies regarding additional booster vaccinations. —PNK
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Written from the paper’s full text.
TL;DR
In a phase 1 mRNA-1273 vaccine cohort, binding and neutralizing antibodies against SARS-CoV-2 variants persisted 6 months after the second dose, but activity against B.1.351 was substantially reduced. By day 209, more than half of subjects still neutralized B.1.351, while all subjects retained binding antibodies to all tested variants.
Key findings
- Sera from n = 24 vaccinees showed low activity after one dose, peak activity at day 43 (2 weeks after dose 2), and moderate declines through day 209 (6 months after dose 2).
- At day 209 in the pseudovirus assay, all sera neutralized D614G and B.1.429, but fewer neutralized WA1 (88%), B.1.1.7 (96%), B.1.617.2 (96%), B.1.526 (88%), P.1 (85%), and B.1.351 (54%).
- In the live-virus FRNT at day 209, all sera neutralized WA1 and D614G, 88% neutralized B.1.1.7, and 58% neutralized B.1.351.
- Binding antibodies to S-2P and RBD of WA1, B.1.1.7, B.1.351, and P.1 were detected in all subjects at all time points; cell-surface spike binding was detected against WA1, D614G, and all six variants at all time points. B.1.351 caused the greatest reduction in titers across assays, and E484K reduced pseudovirus neutralization 2.4-fold.
Methods
- Sera from a random sample of eight volunteers in each of three age groups (18–55, 55–70, and 71+ years; n = 24) in the mRNA-1273 phase 1 trial, collected at days 29, 43, 119, and 209 after first vaccination with two 100-μg doses 28 days apart.
- Humoral responses were assessed with three functional assays (lentivirus-based pseudovirus neutralization, live-virus focus reduction neutralization test, and MSD-ECLIA ACE2 competition) and two binding assays (flow cytometry for cell-surface full-length spike and MSD-ECLIA for soluble S-2P and RBD).
- Variants tested included WA1, D614G, B.1.1.7, B.1.351, P.1, B.1.429, B.1.526, and B.1.617.2, with some variants tested only in subsets or specific assays; analyses used geometric means, ratios, percentages of sera with detectable activity, and paired t tests comparing day 43 with day 209 ratios.
Limitations
- The paper states that it examined a “small number of individuals” and that “additional studies will be needed to address the effect of new variants that will surely arise in areas of intense viral infection.”
- Evident from the text: the study used n = 24 from a phase 1 trial, so age-group comparisons were limited and showed only trends or marginal statistical significance with overlapping groups.
- Evident from the text: the study measured serum antibodies and inferred memory B cell/anamnestic responses without directly assaying memory B cells or clinical protection.
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Claims the paper makes
0 of 27 cited sources checked · 0 supported · 0 flagged
- Findingown data
The ratio of WA1 to B.1.351 binding was greater at day 209 than at day 43 for both S2P and RBD.
“The ratio of WA1 to B.1.351 binding was greater at day 209 than at day 43 for both S2P and RBD, implying a more rapid decay of B.1.351-recognizing antibodies (Fig. 4).”
Quote in the paperSubstantial claim - Findingcitation
Pseudovirus neutralization titers to D614G were threefold higher than to WA1.
“Similar to previous studies from our group (15) and others (18), pseudovirus neutralization titers to D614G were threefold higher than to WA1 (Fig. 2G).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [15] 15. E. J. Anderson, N. G. Rouphael, A. T. Widge, L. A. Jackson, P. C. Roberts, M. Makhene, J. D. Chappell, M. R. Denison, L. J. Stevens, A. J. Pruijssers, A. B. McDermott, B. Flach, B. C. Lin, N. A. Doria-Rose, S. O’Dell, S. D. Schmidt, K. S. Corbett, P. A. Swanson 2nd, M. Padilla, K. M. Neuzil, H. Bennett, B. Leav, M. Makowski, J. Albert, K. Cross, V. V. Edara, K. Floyd, M. S. Suthar, D. R. Martinez, R. Baric, W. Buchanan, C. J. Luke, V. K. Phadke, C. A. Rostad, J. E. Ledgerwood, B. S. Graham, J. H. Beigel, mRNA-1273 Study Group, Safety and Immunogenicity of SARS-CoV-2 mRNA-1273 Vaccine in Ol source
Not checked in the free run.
- cites [18] 18. D. Weissman, M.-G. Alameh, T. de Silva, P. Collini, H. Hornsby, R. Brown, C. C. LaBranche, R. J. Edwards, L. Sutherland, S. Santra, K. Mansouri, S. Gobeil, C. McDanal, N. Pardi, N. Hengartner, P. J.C. Lin, Y. Tam, P. A. Shaw, M. G. Lewis, C. Boesler, U. Şahin, P. Acharya, B. F. Haynes, B. Korber, D. C. Montefiori, D614G Spike Mutation Increases SARS CoV-2 Susceptibility to Neutralization. Cell Host Microbe 29, 23– 31.E4 (2021). 10.1016/j.chom.2020.11.012 33306985 PMC7707640 source
Not checked in the free run.
- Findingown data
High levels of binding antibodies recognizing all tested variants, including B.1.351 and B.1.617.2, were maintained in all subjects over this time period.
“High levels of binding antibodies recognizing all tested variants, including B.1.351 and B.1.617.2, were maintained in all subjects over this time period.”
Quote in the paperSubstantial claim - Findingown data
E484K significantly affected neutralization sensitivity, with a geometric mean 2.4-fold lower ID50.
“By contrast, E484K, present in B.1.351, P.1, and B.1.526, significantly affected neutralization sensitivity, with a geometric mean 2.4-fold lower 50% inhibitory dilution (ID50) (fig. S2).”
Quote in the paperSubstantial claim - Findingown data
Many subjects in the oldest group retained neutralizing activity against the variants 6 months after the second vaccine dose.
“Notably, many subjects in the oldest group retained neutralizing activity against the variants 6 months after the second vaccine dose (fig. S5).”
Quote in the paperSubstantial claim
- Findingown data
The opposite effect was observed for ACE2-competing antibodies and live-virus neutralization against B.1.351.
“However, the opposite effect was observed for ACE2-competing antibodies and live-virus neutralization against B.1.351.”
Quote in the paperSubstantial claim - Findingown data
All subjects had broadly cross-reactive functional activity against all variants at the peak of the response.
“Notably, all subjects had broadly cross-reactive functional activity against all variants at the peak of the response.”
Quote in the paperSubstantial claim - Findingown data
No statistically significant differences over time were noted for pseudovirus neutralization or cell surface spike binding.
“No statistically significant differences over time were noted for pseudovirus neutralization or cell surface spike binding.”
Quote in the paperSubstantial claim - Findingcitation
In the pseudovirus neutralization assay, 25% of sera neutralized WA1 after one dose (day 29).
“In the pseudovirus neutralization assay, consistent with our previous study (13), 25% of sera neutralized WA1 after one dose (day 29).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [13] 13. N. Doria-Rose, M. S. Suthar, M. Makowski, S. O’Connell, A. B. McDermott, B. Flach, J. E. Ledgerwood, J. R. Mascola, B. S. Graham, B. C. Lin, S. O’Dell, S. D. Schmidt, A. T. Widge, V.-V. Edara, E. J. Anderson, L. Lai, K. Floyd, N. G. Rouphael, V. Zarnitsyna, P. C. Roberts, M. Makhene, W. Buchanan, C. J. Luke, J. H. Beigel, L. A. Jackson, K. M. Neuzil, H. Bennett, B. Leav, J. Albert, P. Kunwar, mRNA-1273 Study Group, Antibody Persistence through 6 Months after the Second Dose of mRNA-1273 Vaccine for Covid-19. N. Engl. J. Med. 384, 2259– 2261 (2021). 10.1056/NEJMc2103916 33822494 PMC8524784 source
Not checked in the free run.
- Findingown data
None of the mutations D614G plus N501Y, Y453F, and N439K showed a significant impact on neutralization by day 43 sera.
“None of these mutations showed a significant impact on neutralization by day 43 sera (fig. S2).”
Quote in the paperSubstantial claim - Findingown data
Consistently across assays, low-level recognition of all variants was observed after a single dose (day 29).
“Consistently across assays, low-level recognition of all variants was observed after a single dose (day 29) (Fig. 1).”
Quote in the paperNot a substantial claim - Findingown data
The same patterns were observed for B.1.1.7.
“The same patterns were observed for B.1.1.7.”
Quote in the paperSubstantial claim - Findingown data
Binding antibodies to S-2P and RBD of WA1, B.1.1.7, B.1.351, and P.1 sequences were detected in all subjects at all time points.
“Antibodies that bound to S-2P and RBD of the WA1, B.1.1.7, B.1.351, and P.1 sequences were detected in all subjects at all time points.”
Quote in the paperSubstantial claim - Findingown data
Binding to full-length cell surface-expressed spike was detected against WA1, D614G, and all six variants at all time points.
“Likewise, binding to full-length cell surface–expressed spike was detected against WA1, D614G, and all six variants at all time points.”
Quote in the paperSubstantial claim - Findingown data
In the live-virus FRNT neutralization assay, titers to WA1 were higher than those to D614G.
“By contrast, using the live-virus FRNT neutralization assay (Fig. 1B and Fig. 2B), titers to WA1 were higher than those to D614G, consistent with previous studies of that assay (19).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [19] 19. V. V. Edara, W. H. Hudson, X. Xie, R. Ahmed, M. S. Suthar, Neutralizing Antibodies Against SARS-CoV-2 Variants After Infection and Vaccination. JAMA 325, 1896– 1898 (2021). 10.1001/jama.2021.4388 33739374 PMC7980146 source
Not checked in the free run.
- Findingown data
In all assays, B.1.351 was the variant that caused the greatest reduction in titers compared with WA1 or D614G.
“In all assays, B.1.351 was the variant that caused the greatest reduction in titers compared with WA1 or D614G.”
Quote in the paperSubstantial claim - Findingown data
The ACE2 competition assay showed reduced activity against B.1.351 at the later time points.
“Moreover, the ACE2 competition assay showed reduced activity against B.1.351 at the later time points (Fig. 3).”
Quote in the paperSubstantial claim - Findingown data
Two weeks after the second dose (day 43), all sera neutralized all of the pseudoviruses.
“Two weeks after the second dose (day 43), all sera neutralized all of the pseudoviruses.”
Quote in the paperSubstantial claim - Findingown data
Results from diverse methodologies showed similar dynamics over 7 months after the first vaccination.
“The results from these diverse methodologies also showed similar dynamics over 7 months after the first vaccination.”
Quote in the paperNot a substantial claim - Interpretationown data
The greater ratio of WA1 to B.1.351 binding at day 209 than at day 43 implies a more rapid decay of B.1.351-recognizing antibodies.
“The ratio of WA1 to B.1.351 binding was greater at day 209 than at day 43 for both S2P and RBD, implying a more rapid decay of B.1.351-recognizing antibodies (Fig. 4).”
Quote in the paperSubstantial claim - Premisecitation
Clinical studies have reported somewhat reduced efficacy and effectiveness against the B.1.1.7, B.1.351, and B.1.617.2 variants.
“Likewise, clinical studies have reported somewhat reduced efficacy and effectiveness against the B.1.1.7, B.1.351, and B.1.617.2 variants (10–12).”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites [10] 10. L. J. Abu-Raddad, H. Chemaitelly, A. A. Butt, National Study Group for COVID-19 Vaccination, Effectiveness of the BNT162b2 Covid-19 Vaccine against the B.1.1.7 and B.1.351 Variants. N. Engl. J. Med. 385, 187– 189 (2021). 10.1056/NEJMc2104974 33951357 PMC8117967 source
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- Premisecitation
B.1.351 was the most resistant to neutralization by convalescent or vaccinee sera, with 6- to 15-fold less neutralization activity for sera from individuals immunized with vaccines based on the WA1 strain.
“In multiple studies, B.1.351 was the most resistant to neutralization by convalescent or vaccinee sera, with 6- to 15-fold less neutralization activity for sera from individuals immunized with vaccines based on the virus strain first described in January 2020 (Wuhan-Hu-1, spike also called WA1) (2–9).”
Quote in the paperNot a substantial claim0 of 8 sources checked- cites [2] 2. V. V. Edara, C. Norwood, K. Floyd, L. Lai, M. E. Davis-Gardner, W. H. Hudson, G. Mantus, L. E. Nyhoff, M. W. Adelman, R. Fineman, S. Patel, R. Byram, D. N. Gomes, G. Michael, H. Abdullahi, N. Beydoun, B. Panganiban, N. McNair, K. Hellmeister, J. Pitts, J. Winters, J. Kleinhenz, J. Usher, J. B. O’Keefe, A. Piantadosi, J. J. Waggoner, A. Babiker, D. S. Stephens, E. J. Anderson, S. Edupuganti, N. Rouphael, R. Ahmed, J. Wrammert, M. S. Suthar, Infection- and vaccine-induced antibody binding and neutralization of the B.1.351 SARS-CoV-2 variant. Cell Host Microbe 29, 516– 521.E3 (2021). 10.1016/j source
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- cites [3] 3. M. Hoffmann, P. Arora, R. Groß, A. Seidel, B. F. Hörnich, A. S. Hahn, N. Krüger, L. Graichen, H. Hofmann-Winkler, A. Kempf, M. S. Winkler, S. Schulz, H.-M. Jäck, B. Jahrsdörfer, H. Schrezenmeier, M. Müller, A. Kleger, J. Münch, S. Pöhlmann, SARS-CoV-2 variants B.1.351 and P.1 escape from neutralizing antibodies. Cell 184, 2384– 2393.E12 (2021). 10.1016/j.cell.2021.03.036 33794143 PMC7980144 source
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- cites [4] 4. X. Shen, H. Tang, R. Pajon, G. Smith, G. M. Glenn, W. Shi, B. Korber, D. C. Montefiori, Neutralization of SARS-CoV-2 Variants B.1.429 and B.1.351. N. Engl. J. Med. 384, 2352– 2354 (2021). 10.1056/NEJMc2103740 33826819 PMC8063884 source
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- Interpretationreasoning
Individuals who demonstrate waning immune responses over time are likely to have memory B cells capable of delivering an anamnestic response to those variants in the event of exposure to virus, or potentially with an additional dose of vaccine.
“Thus, individuals who demonstrate waning immune responses over time are likely to have memory B cells capable of delivering an anamnestic response to those variants in the event of exposure to virus, or potentially with an additional dose of vaccine.”
Quote in the paperSubstantial claim
- May combine two claims. 17
- Classified as probably not a substantial claim. 4
May combine two claims.
Findingown dataIn the live-virus assay at day 29, most sera neutralized WA1, D614G, and B.1.1.7, but only 8% neutralized B.1.351, and ACE2 competition of binding to B.1.351 RBD was detected in 63% of sera.
“Similarly, in the live-virus assay, most day 29 sera neutralized WA1, D614G, and B.1.1.7, but only 8% neutralized B.1.351, and ACE2 competition of binding to B.1.351 RBD was detected in 63% of sera.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataAt day 209, all sera neutralized D614G and B.1.429 in the pseudovirus assay, but fewer sera neutralized other variants, with 88, 96, 96, 88, 85, and 54% of sera neutralizing WA1, B.1.1.7, B.1.617.2, B.1.526, P.1, and B.1.351, respectively.
“Responses waned over time: All sera from 6 months after the second dose (day 209) neutralized D614G and B.1.429 in this assay, but fewer sera neutralized the other variants, with 88, 96, 96, 88, 85, and 54% of sera neutralizing WA1, B.1.1.7, B.1.617.2, B.1.526, P.1, and B.1.351, respectively.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataDifferences in titers between age groups were small, and there was overlap between groups.
“Differences were small, and there was overlap between groups (figs. S3 to S5).”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataIn the live-virus assay, all sera were active against WA1, D614G, B.1.1.7, and B.1.351 at day 43; at day 209, all sera neutralized WA1 and D614G, 88% neutralized B.1.1.7, and 58% neutralized B.1.351.
“Similarly, using the live-virus assay, all sera were active against WA1, D614G, B.1.1.7, and B.1.351 at day 43, and at day 209, all sera neutralized WA1 and D614G, 88% of sera neutralized B.1.1.7, and 58% neutralized B.1.351.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataIn the pseudovirus assay, neutralizing activity was highest against D614G and lowest against B.1.351, with values for all other variants tested falling between those two variants.
“Using the pseudovirus assay, the neutralizing activity was highest against D614G and lowest against B.1.351, with values for all other variants tested falling between those two variants (Fig. 1A and Fig. 2A).”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Findingown dataValues obtained for each assay on a per-sample basis correlated with each other.
“Notably, the values obtained for each assay on a per-sample basis correlated with each other (fig. S1).”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataIn the cell surface spike binding assay, WA1 and D614G were nearly indistinguishable, with ~1.5-fold reduced binding to B.1.1.7, B.1.526, and B.1.617.2 and 2.4- to 3.0-fold reduced binding to P.1, B.1.429, and B.1.351.
“In this assay (Fig. 1D and Fig. 2D), WA1 and D614G were nearly indistinguishable, with ~1.5-fold reduced binding to B.1.1.7, B.1.526, and B.1.617.2 and 2.4- to 3.0-fold reduced binding to P.1, B.1.429, and B.1.351.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataCollectively, the functional assays revealed a decreased frequency of sera with detectable activity against B.1.351 and other variants after a single dose or 6 months after the second dose.
“Collectively, the functional assays revealed a decreased frequency of sera with detectable activity against B.1.351 and other variants after a single dose or 6 months after the second dose.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown datamRNA-1273-elicited antibody activity against SARS-CoV-2 variants persisted 6 months after the second dose, albeit at reduced levels compared with peak activity, with more than half of subjects maintaining neutralizing activity against B.1.351 at the latest time point tested.
“mRNA-1273–elicited antibody activity against SARS-CoV-2 variants persisted 6 months after the second dose, albeit at reduced levels compared with peak activity, with more than half of subjects maintaining neutralizing activity against B.1.351 at the latest time point tested.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataACE2 competition was highest for WA1 RBD, intermediate for B.1.1.7, and lowest for B.1.351.
“ACE2 competition was highest for WA1 RBD, intermediate for B.1.1.7, and lowest for B.1.351 (Fig. 1C and Fig. 2C).”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataIn this study, there was a trend to lower titers against SARS-CoV-2 spike variants in the oldest individuals at day 209, with marginally statistically significant differences in some assays for some variants.
“Here, we observed a trend to lower titers against SARS-CoV-2 spike variants in the oldest individuals at day 209, with marginally statistically significant differences in some assays for some variants.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataActivity against all variants peaked 2 weeks after the second dose (day 43), with moderate declines over time through day 209.
“Activity against all variants peaked 2 weeks after the second dose (day 43), with moderate declines over time through day 209 (Fig. 1).”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataIn the pseudovirus neutralization assay at day 29, 83% of sera neutralized D614G, 33% neutralized B.1.1.7, and only 8% could neutralize B.1.351.
“In contrast, 83% of day 29 sera neutralized D614G, which is more sensitive than WA1 in this assay as noted above, but 33% neutralized B.1.1.7 and only 8% could neutralize B.1.351.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataFor all other variants, the effect in the live-virus and pseudovirus neutralization assays was concordant: titers against B.1.1.7 were similar to D614G and lower against B.1.351.
“For all other variants, the effect in the live-virus and pseudovirus neutralization assays were concordant: titers against B.1.1.7 were similar to D614G and lower against B.1.351.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataThe ECLIA assay showed slightly reduced binding to variant S-2P and RBD proteins, with rank order of highest to lowest binding: WA1, B.1.1.7, P.1, and B.1.351.
“The ECLIA assay showed slightly reduced binding to the variant S-2P (Fig. 1E and Fig. 2E) and RBD (Fig. 1F and Fig. 2F) proteins, with the rank order of highest to lowest binding as follows: WA1, B.1.1.7, P.1, and B.1.351.”
Quote in the paperSubstantial claimMay combine two claims.
Interpretationown dataThese data suggest that although binding antibodies to variants decayed faster than antibodies to WA1, the functional antibodies to variants may have diminished more slowly.
“These data suggest that although binding antibodies to variants decayed faster than antibodies to WA1, the functional antibodies to variants may have diminished more slowly.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationMost prior studies evaluated sera from vaccinated individuals soon after the first or second dose and had limited data on the durability of such responses.
“Most of these prior studies have evaluated sera from vaccinated individuals at time points soon after the first or second dose and have had limited data on the durability of such responses.”
Quote in the paperSubstantial claim0 of 8 sources checked- cites [2] 2. V. V. Edara, C. Norwood, K. Floyd, L. Lai, M. E. Davis-Gardner, W. H. Hudson, G. Mantus, L. E. Nyhoff, M. W. Adelman, R. Fineman, S. Patel, R. Byram, D. N. Gomes, G. Michael, H. Abdullahi, N. Beydoun, B. Panganiban, N. McNair, K. Hellmeister, J. Pitts, J. Winters, J. Kleinhenz, J. Usher, J. B. O’Keefe, A. Piantadosi, J. J. Waggoner, A. Babiker, D. S. Stephens, E. J. Anderson, S. Edupuganti, N. Rouphael, R. Ahmed, J. Wrammert, M. S. Suthar, Infection- and vaccine-induced antibody binding and neutralization of the B.1.351 SARS-CoV-2 variant. Cell Host Microbe 29, 516– 521.E3 (2021). 10.1016/j source
Not checked in the free run.
- cites [3] 3. M. Hoffmann, P. Arora, R. Groß, A. Seidel, B. F. Hörnich, A. S. Hahn, N. Krüger, L. Graichen, H. Hofmann-Winkler, A. Kempf, M. S. Winkler, S. Schulz, H.-M. Jäck, B. Jahrsdörfer, H. Schrezenmeier, M. Müller, A. Kleger, J. Münch, S. Pöhlmann, SARS-CoV-2 variants B.1.351 and P.1 escape from neutralizing antibodies. Cell 184, 2384– 2393.E12 (2021). 10.1016/j.cell.2021.03.036 33794143 PMC7980144 source
Not checked in the free run.
- cites [4] 4. X. Shen, H. Tang, R. Pajon, G. Smith, G. M. Glenn, W. Shi, B. Korber, D. C. Montefiori, Neutralization of SARS-CoV-2 Variants B.1.429 and B.1.351. N. Engl. J. Med. 384, 2352– 2354 (2021). 10.1056/NEJMc2103740 33826819 PMC8063884 source
Not checked in the free run.
- cites [5] 5. 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. Nature 593, 130– 135 (2021). 10.1038/s41586-021-03398-2 33684923 source
Not checked in the free run.
- cites [6] 6. C. K. Wibmer, F. Ayres, T. Hermanus, M. Madzivhandila, P. Kgagudi, B. Oosthuysen, B. E. Lambson, T. de Oliveira, M. Vermeulen, K. van der Berg, T. Rossouw, M. Boswell, V. Ueckermann, S. Meiring, A. von Gottberg, C. Cohen, L. Morris, J. N. Bhiman, P. L. Moore, SARS-CoV-2 501Y.V2 escapes neutralization by South African COVID-19 donor plasma. Nat. Med. 27, 622– 625 (2021). 10.1038/s41591-021-01285-x 33654292 source
Not checked in the free run.
- cites [7] 7. 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.
- cites [8] 8. D. H. Barouch, K. E. Stephenson, J. Sadoff, J. Yu, A. Chang, M. Gebre, K. McMahan, J. Liu, A. Chandrashekar, S. Patel, M. Le Gars, A. M. de Groot, D. Heerwegh, F. Struyf, M. Douoguih, J. van Hoof, H. Schuitemaker, Durable Humoral and Cellular Immune Responses 8 Months after Ad26.COV2.S Vaccination. N. Engl. J. Med. 10.1056/NEJMc2108829 (2021). 10.1056/NEJMc2108829 34260834 PMC8314733 source
Not checked in the free run.
- cites [9] 9. N. Zhu, D. Zhang, W. Wang, X. Li, B. Yang, J. Song, X. Zhao, B. Huang, W. Shi, R. Lu, P. Niu, F. Zhan, X. Ma, D. Wang, W. Xu, G. Wu, G. F. Gao, W. Tan, China Novel Coronavirus Investigating and Research Team, A Novel Coronavirus from Patients with Pneumonia in China, 2019. N. Engl. J. Med. 382, 727– 733 (2020). 10.1056/NEJMoa2001017 31978945 PMC7092803 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationImmune responses to vaccination are often weaker in older adults.
“Immune responses to vaccination are often weaker in older adults (26).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [26] 26. A. Ciabattini, C. Nardini, F. Santoro, P. Garagnani, C. Franceschi, D. Medaglini, Vaccination in the elderly: The challenge of immune changes with aging. Semin. Immunol. 40, 83– 94 (2018). 10.1016/j.smim.2018.10.010 30501873 source
Not checked in the free run.
May combine two claims.
PremisecitationVaccination with mRNA-1273 elicited antibodies to SARS-CoV-2 WA1 in subjects aged 56 to 70 and 71 and older that are as potent and durable as those elicited in adults aged 18 to 55, with a slight decrease in potency for the oldest subjects in live-virus neutralization.
“We previously showed that vaccination with mRNA-1273 elicited antibodies to SARS-CoV-2 WA1 in subjects aged 56 to 70 and 71 and older that are as potent (15) and durable (13) as those elicited in adults aged 18 to 55, with a slight decrease in potency for the oldest subjects in live-virus neutralization (13).”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [15] 15. E. J. Anderson, N. G. Rouphael, A. T. Widge, L. A. Jackson, P. C. Roberts, M. Makhene, J. D. Chappell, M. R. Denison, L. J. Stevens, A. J. Pruijssers, A. B. McDermott, B. Flach, B. C. Lin, N. A. Doria-Rose, S. O’Dell, S. D. Schmidt, K. S. Corbett, P. A. Swanson 2nd, M. Padilla, K. M. Neuzil, H. Bennett, B. Leav, M. Makowski, J. Albert, K. Cross, V. V. Edara, K. Floyd, M. S. Suthar, D. R. Martinez, R. Baric, W. Buchanan, C. J. Luke, V. K. Phadke, C. A. Rostad, J. E. Ledgerwood, B. S. Graham, J. H. Beigel, mRNA-1273 Study Group, Safety and Immunogenicity of SARS-CoV-2 mRNA-1273 Vaccine in Ol source
Not checked in the free run.
- cites [13] 13. N. Doria-Rose, M. S. Suthar, M. Makowski, S. O’Connell, A. B. McDermott, B. Flach, J. E. Ledgerwood, J. R. Mascola, B. S. Graham, B. C. Lin, S. O’Dell, S. D. Schmidt, A. T. Widge, V.-V. Edara, E. J. Anderson, L. Lai, K. Floyd, N. G. Rouphael, V. Zarnitsyna, P. C. Roberts, M. Makhene, W. Buchanan, C. J. Luke, J. H. Beigel, L. A. Jackson, K. M. Neuzil, H. Bennett, B. Leav, J. Albert, P. Kunwar, mRNA-1273 Study Group, Antibody Persistence through 6 Months after the Second Dose of mRNA-1273 Vaccine for Covid-19. N. Engl. J. Med. 384, 2259– 2261 (2021). 10.1056/NEJMc2103916 33822494 PMC8524784 source
Not checked in the free run.
Probably not a substantial claim: may not pass S2 (checkable).
Interpretationown dataThe authors' data are encouraging for the use of this vaccine in the face of viral variation.
“Although additional studies will be needed to address the effect of new variants that will surely arise in areas of intense viral infection, our data are encouraging for the use of this vaccine in the face of viral variation.”
Quote in the paperNot a substantial claim- Rests on an assumption: Neutralizing and binding antibody levels against SARS-CoV-2 variants are correlates of protection against COVID-19.
Classified as probably not a substantial claim.
PremisecitationConvalescent individuals develop B cell lineages that mature over time, increasing their activity against SARS-CoV-2 variants.
“Convalescent individuals develop B cell lineages that mature over time, increasing their activity against SARS-CoV-2 variants (27).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [27] 27. Z. Wang, F. Muecksch, D. Schaefer-Babajew, S. Finkin, C. Viant, C. Gaebler, H.-H. Hoffmann, C. O. Barnes, M. Cipolla, V. Ramos, T. Y. Oliveira, A. Cho, F. Schmidt, J. Da Silva, E. Bednarski, L. Aguado, J. Yee, M. Daga, M. Turroja, K. G. Millard, M. Jankovic, A. Gazumyan, Z. Zhao, C. M. Rice, P. D. Bieniasz, M. Caskey, T. Hatziioannou, M. C. Nussenzweig, Naturally enhanced neutralizing breadth against SARS-CoV-2 one year after infection. Nature 595, 426– 431 (2021). 10.1038/s41586-021-03696-9 34126625 PMC8277577 source
Not checked in the free run.
The paper relies on this without support.
Neutralizing and binding antibody levels against SARS-CoV-2 variants are correlates of protection against COVID-19.
“Although additional studies will be needed to address the effect of new variants that will surely arise in areas of intense viral infection, our data are encouraging for the use of this vaccine in the face of viral variation.”
The paper relies on this without support.
The pseudovirus neutralization, live-virus FRNT, ACE2 competition, and binding assays used here measure humoral immune responses relevant to protection against SARS-CoV-2 variants.
“Three functional assays and two binding assays were used to assess the humoral immune response to the SARS-CoV-2 spike protein.”
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?
Of plasma samples from recipients of an mRNA vaccine, about 30% display 3-fold to 10-fold reduced neutralizing activity against the Iota variant.
“Of plasma samples from recipients of an mRNA vaccine, about 30% display 3-fold to 10-fold reduced neutralizing activity 230,235 .”
From The biological and clinical significance of emerging SARS-CoV-2 variants (2021) · cites this paper as [230]
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.
Variant-to-WA1 ratios are described in the opposite direction from Fig. 4
MinorThe methods description says the ratios were variant activity divided by WA1 activity, whereas the Fig. 4 caption says they were WA1 activity divided by variant activity.
“for each time point, we calculated the ratios of activity against each variant to WA1.”
“Symbols show the value for WA1 divided by the value for the indicated variant for each sample.”
Day-209 P.1 percentage is incompatible with the stated sample count
MinorWith 24 sera at a time point, no whole number of positive sera produces 85% when rounded to the nearest percent. The figure caption states that its percentages use 24 sera at each time point, including for each variant.
“85, and 54% of sera neutralizing WA1, B.1.1.7, B.1.617.2, B.1.526, P.1, and B.1.351, respectively.”
“Values are the percentage of sera (n = 24 at each time point) for which antibodies were detected for each variant.”
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mRNA vaccines for infectious diseases: principles, delivery and clinical translation
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Self-citationProtective activity of mRNA vaccines against ancestral and variant SARS-CoV-2 strains
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- Authors
- Pegu, A., O’Connell, S. E., Schmidt, S. D., O’Dell, S., Talana, C. A., Lai, L., Albert, J., Anderson, E., Bennett, H., Corbett, K. S., Flach, B., Jackson, L., Leav, B., Ledgerwood, J. E., Luke, C. J., Makowski, M., Nason, M. C., Roberts, P. C., Roederer, M., Rebolledo, P. A., Rostad, C. A., Rouphael, N. G., Shi, W., Wang, L., Widge, A. T., Yang, E. S., The mRNA-1273 Study Group§, Beigel, J. H., Graham, B. S., Mascola, J. R., Suthar, M. S., McDermott, A. B., Doria-Rose, N. A., Arega, J., Beigel, J. H., Buchanan, W., Elsafy, M., Hoang, B., Lampley, R., Kolhekar, A., Koo, H., Luke, C., Makhene, M., Nayak, S., Pikaart-Tautges, R., Roberts, P. C., Russell, J., Sindall, E., Albert, J., Kunwar, P., Makowski, M., Anderson, E. J., Bechnak, A., Bower, M., Camacho-Gonzalez, A. F., Collins, M., Drobeniuc, A., Edara, V. V., Edupuganti, S., Floyd, K., Gibson, T., Ackerley, C. M. G., Johnson, B., Kamidani, S., Kao, C., Kelley, C., Lai, L., Macenczak, H., McCullough, M. P., Peters, E., Phadke, V. K., Rebolledo, P. A., Rostad, C. A., Rouphael, N., Scherer, E., Sherman, A., Stephens, K., Suthar, M. S., Teherani, M., Traenkner, J., Winston, J., Yildirim, I., Barr, L., Benoit, J., Carste, B., Choe, J., Dunstan, M., Erolin, R., ffitch, J., Fields, C., Jackson, L. A., Kiniry, E., Lasicka, S., Lee, S., Nguyen, M., Pimienta, S., Suyehira, J., Witte, M., Bennett, H., Altaras, N. E., Carfi, A., Hurley, M., Leav, B., Pajon, R., Sun, W., Zaks, T., Coler, R. N., Larsen, S. E., Neuzil, K. M., Lindesmith, L. C., Martinez, D. R., Munt, J., Mallory, M., Edwards, C., Baric, R. S., Berkowitz, N. M., Boritz, E. A., Carlton, K., Corbett, K. S., Costner, P., Creanga, A., Doria-Rose, N. A., Douek, D. C., Flach, B., Gaudinski, M., Gordon, I., Graham, B. S., Holman, L., Ledgerwood, J. E., Leung, K., Lin, B. C., Louder, M. K., Mascola, J. R., McDermott, A. B., Morabito, K. M., Novik, L., O’Connell, S., O’Dell, S., Padilla, M., Pegu, A., Schmidt, S. D., Shi, W., Swanson, P. A., Talana, C. A., Wang, L., Widge, A. T., Yang, E. S., Zhang, Y., Chappell, J. D., Denison, M. R., Hughes, T., Lu, X., Pruijssers, A. J., Stevens, L. J., Posavad, C. M., Gale, M., Menachery, V., & Shi, P.-Y.
- Affiliations
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
- Department of Pediatrics, Division of Infectious Disease, Emory Vaccine Center, Yerkes National Primate Research Center, Emory University School of Medicine, Atlanta, GA 30322, USA.
- Kaiser Permanente Washington Health Research Institute, Seattle, WA 98101, USA.
- Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
- National Institutes of Health (US)
- Hope Clinic, Department of Medicine, Emory University School of Medicine, Decatur, GA 30030, USA.
- Emmes (United States) (US)
- Emory University (US)
- Kaiser Permanente Washington Health Research Institute (US)
- Moderna Therapeutics (United States) (US)
- ORCID
- Anderson, Evan
- Jackson, Lisa
- Nason, Martha C.
- Roederer, Mario
- Rouphael, Nadine G.
- Nayak, Seema
- Collins, Matthew
- Edara, Venkata Viswanadh
- Edupuganti, Srilatha
- Floyd, Katharine
- Kamidani, Satoshi
- Kao, Carol
- Kelley, Colleen
- Phadke, Varun K.
- Scherer, Erin
- Sherman, Amy
- Teherani, Mehgan
- Yildirim, Inci
- Fields, Colin
- Lee, Stella
- Coler, Rhea N.
- Larsen, Sasha E.
- Neuzil, Kathleen M.
- Lindesmith, Lisa C.
- Martinez, David R.
- Munt, Jennifer
- Mallory, Michael
- Edwards, Caitlin
- Baric, Ralph S.
- Boritz, Eli A.
- Carlton, Kevin
- Creanga, Adrian
- Douek, Daniel C.
- Gaudinski, Martin
- Gordon, Ingelise
- Holman, LaSonji
- Leung, Kwanyee
- Lin, Bob C.
- Louder, Mark K.
- Morabito, Kaitlyn M.
- Novik, Laura
- Swanson, Phillip A.
- Zhang, Yi
- Chappell, James D.
- Denison, Mark R.
- Hughes, Tia
- Lu, Xiaotao
- Pruijssers, Andrea J.
- Stevens, Laura J.
- Posavad, Christine M.
- Gale, Michael
- Menachery, Vineet
- Shi, Pei-Yong
- Venue
- Science
- Published
- 2021-09-17
- Volume
- 373
- Issue
- 6561
- Pages
- 1372-1377
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC8691522
- OpenAlex
- W3189544042
- Cited by
- 527
- References
- 31
- Citations by year
- 2026: 21 · 2025: 35 · 2024: 54 · 2023: 118 · 2022: 234 · 2021: 65
- FWCI
- 37.53
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Science (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (UM1AI148373, UM1AI148576, UM1AI148684, P51OD011132, HHSN272201500002C)
- Woodruff Health Sciences Center (2020 COVID-19 CURE AWARD)
- Emory Executive Vice President for Health Affairs Synergy Fund Award
- Intramural Research Program of the Vaccine Research Center, NIAID, NIH
- Vaccine Research Center (TMPRSS2)
- Coalition for Epidemic Preparedness Innovations
- Pediatric Research Alliance Center for Childhood Infections and Vaccines and Children’s Healthcare of Atlanta
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
- Keywords
- mRNA-1273 vaccine, SARS-CoV-2 variants, antibody persistence, neutralizing antibodies, Beta variant, Delta variant, Alpha variant, Gamma variant, Epsilon variant, immunological cross-reactivity, booster vaccination, antibody waning
- MeSH terms
- Immunogenicity, Vaccine, COVID-19, SARS-CoV-2, COVID-19 Vaccines, 2019-nCoV Vaccine mRNA-1273, Adolescent, Adult, Aged, Antibodies, Viral, Cross Reactions, Humans, Immunization, Secondary, Middle Aged, Time Factors, Young Adult, Immune Evasion, Antibodies, Neutralizing
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.
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