Sensitivity of infectious SARS-CoV-2 B.1.1.7 and B.1.351 variants to neutralizing antibodies

May combine two claims.

Convalescent sera bound similarly to all three S proteins, although B.1.351 showed a slight reduction that was statistically significant at M6.

“Overall, the sera bound similarly to all three S proteins, even though B.1.351displayed a slight reduction (statistically significant at M6) in the mean fluorescence intensity (MFI) of binding (Fig. 3c).”

May combine two claims.

In the second cohort at M9, 93% of individuals neutralized D614G or B.1.1.7, whereas only 63% neutralized B.1.351.

“The fraction of neutralizers was higher in the second cohort, with 93% of individuals neutralizing either D614G or B.1.1.7 strains at M9.In contrast, only 63% of individuals neutralized the B.1.351strain (Fig. 2c).”

May combine two claims.

mAb48 bound D614G efficiently, slightly less to B.1.1.7, and lost all binding to B.1.351.

“mAb48 efficiently bound to D614G S proteins, slightly less potently to B.1.1.7,and lost all binding activity to B.1.351.”

May combine two claims.

At week 2, 2 of 15 recipients (13%) neutralized B.1.1.7, and none neutralized B.1.351.

“These low titers were less efficient against B.1.1.7,with 2 of 15 neutralizers (13%), and were inactive against B.1.351(Fig. 4b,c).”

May combine two claims.

At week 3, neutralizing activity increased against D614G and B.1.1.7, with a threefold reduction in titers against B.1.1.7, while B.1.351 remained insensitive.

“At week 3, the neutralizing activity increased against D614G and B.1.1.7.There was, however, a threefold reduction in the neutralization titers against B.1.1.7 (Fig. 4b), whereas B.1.351remained insensitive.”

May combine two claims.

Ten pre-pandemic nasopharyngeal swab specimens were all negative for neutralizing SARS-CoV-2 antibodies starting at a 1:4 dilution, ruling out a confounding nonspecific effect.

“The samples were all negative starting at a 1:4 dilution, ruling out a confounding nonspecific effect of a substance that may be present in the swabs (Supplementary Fig. 2).”

May combine two claims.

At week 3, 63%, 38%, and 0% of samples neutralized D614G, B.1.1.7, and B.1.351, respectively.

“At week 3, 63%, 38% and 0% of the samples neutralized D614G, B.1.1.7 and B.1.351strains, respectively (Fig. 4d).”

May combine two claims.

At week 6, 92% of samples neutralized D614G and B.1.1.7, while 77% neutralized B.1.351 with a low titer.

“At week 6, 92% of the samples neutralized D614G and B.1.1.7,whereas 77% neutralized B.1.351with a low titer (Fig. 4d).”

May combine two claims.

In the Orléans convalescent cohort at M3, median ED50 values were 1.5×10^3 for D614G and 1×10^3 for B.1.1.7.

“At M3, the ED 50 values were 1.5 × 10 3 and 1 × 10 3 for D614G and B.1.1.7 variants, respectively”

May combine two claims.

At week 3 after the second dose, titers increased in most recipients and were similar between D614G and B.1.1.7.

“At the last time point (week 3 after the second dose), titers increased in most of the recipients and were similar between D614G and B.1.1.7.”

May combine two claims.

In nasal swabs, SARS-CoV-2 S-protein-binding antibodies were detected in 7 of 13 available samples at week 3 and 14 of 15 samples at week 4.

“In the swabs, we detected SARS-CoV-2 S-protein-binding antibodies in 7 of 13 available samples at week 3, and 14 of 15 samples at week 4 (Extended Data Fig. 2f).”

May combine two claims.

The B.1.351 variant is less sensitive or even insensitive to sera from immunized individuals.

“The B.1.351variant is potentially more problematic as it is less sensitive or even insensitive to sera from immunized individuals.”

May combine two claims.

mAb48 neutralized D614G with an IC50 of 0.1 μg/ml but was inactive against B.1.1.7 and B.1.351.

“MAb48 neutralized D614G (IC 50 of 0.1 µg ml -1 ) but was inactive against B.1.1.7 and B.1.351variants (Fig. 1c,d).”

May combine two claims.

In three vaccine recipients who were seropositive for anti-N at vaccination, serum neutralizing titers were strikingly high at week 2 after the first dose (ED50 about 10^4) and remained similarly high at week 5.

“In these three individuals, the serum neutralizing titers were strikingly high at week 2 after the first dose (ED 50 of about 10 4 ; Extended Data Fig. 2c) and remained similarly high at week 5 (data not shown).”

May combine two claims.

In the Strasbourg cohort at M9, there was no significant difference in neutralization between D614G and B.1.1.7, with similar ED50 of 2×10^2.

“There was no significant difference in neutralization between D614G and B.1.1.7 strains, with a similar ED 50 of 2 × 10 2 .”

The quote only partly states this claim.

Neutralization titers in the Orléans convalescent cohort did not strongly decline between M3 and M6.

“and the values did not strongly decline at M6.”

May combine two claims.

Most individuals neutralized all three strains at M3; the fraction of neutralizers declined at M6, and this decline was more marked for B.1.351.

“Most individuals neutralized the three strains at M3.The fraction of neutralizers started to decline at M6, a phenomenon which was more marked for B.1.351.”

May combine two claims.

Their nasal swabs neutralized D614G and B.1.117 strains similarly but were inactive against B.1.351.

“Their nasal swabs neutralized D614G and B.1.117strains similarly but were inactive against B.1.351.”

May combine two claims.

mAb102 neutralized D614G, B.1.1.7, and B.1.351 similarly, with an IC50 of about 0.01 μg/ml.

“MAb102 efficiently and similarly neutralized the three viral strains, with an IC 50 of ≃0.01 µg ml -1 (Fig. 1c,d).”

May combine two claims.

In the Strasbourg cohort at M9, neutralizing activity against B.1.351 was particularly low, with a median ED50 of 50, representing a fourfold decrease compared with D614G.

“In sharp contrast, the neutralizing activity against B.1.351was particularly low at this late time point, with a median ED 50 of 50, representing a fourfold decrease when compared to D614G (Fig. 2b).”

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

Monoclonal antibodies mAb48 and mAb102 recognize the receptor-binding domain, and mAb10 binds a conserved region of the S2 domain of the S protein.

“Monoclonal antibodies mAb48 and mAb102 recognize the RBD, and mAb10 binds to a conserved region of the S2 domain of the S protein.”

May combine two claims.

In a representative vaccine recipient, serum neutralized only D614G at week 2; B.1.1.7 began to be neutralized at week 3, less efficiently than D614G; B.1.1.7 and D614G were similarly neutralized at week 4; and the anti-B.1.351 response was negative through week 3 and became detectable at week 4 at a level lower than the other two viruses.

“In this instance, the serum only neutralized D614G at week 2, whereas B.1.1.7 started to be neutralized at week 3, although less efficiently than D614G.B.1.1.7 and D614G strains were similarly neutralized at week 4.The anti-B.1.351response was negative up to week 3, and became detectable at week 4, at a level lower than the two other viruses.”

May combine two claims.

Neutralization by vaccine recipient sera differed significantly between strains at week 2 (D614G vs B.1.1.7 P = 0.0105; D614G vs B.1.351 P = 0.008), week 3 (D614G vs B.1.351 P = 0.0002), week 4 (D614G vs B.1.351 P = 0.011; B.1.1.7 vs B.1.351 P = 0.0052) and week 6 (D614G vs B.1.1.7 P = 0.0324; D614G vs B.1.351 P = 0.0324; B.1.1.7 vs B.1.351 P < 0.0001).

“W2: D614G versus B.1.1.7,P = 0.0105; D614G versus B.1.351,P = 0.008.W3: D614G versus B.1.351,P = 0.0002.W4: D614G versus B.1.351,P = 0.011; B.1.1.7 versus B.1.351,P = 0.0052.W6: D614G versus B.1.1.7,P = 0.0324; D614G versus B.1.351,P = 0.0324; B.1.1.7 versus B.1.351,P < 0.0001.”

• AssumptionRests on an assumption: The absence of preexisting anti-S-protein and anti-nucleoprotein antibodies indicates that a vaccine recipient had not previously been infected with SARS-CoV-2.

May combine two claims.

At month 6, convalescent sera from severe cases showed significant differences between D614G and B.1.351 (p = 0.0417) and between B.1.1.7 and B.1.351 (p = 0.011), and sera from mild-to-moderate cases showed a difference between B.1.1.7 and B.1.351 (p = 0.0315).

“M6 (Severe): D614G versus B.1.351p = 0.0417; B.1.1.7 versus B.1.351p = 0.011.M6 (Mild-to-Moderate): B.1.1.7 versus B.1.351p = 0.0315.”

May combine two claims.

The second dose of the Pfizer Cominarty vaccine was associated with a strong increase in neutralizing antibody titers and a widening of strain cross-reactive antibody responses.

“Our study also highlights the importance of the second dose of the Pfizer Cominarty vaccine, which was associated with a strong increase of neutralizing antibody titers and a widening of strain cross-reactive antibody responses.”

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

Neutralization titers measured by the S-Fuse reporter assay correlate with those from a pseudovirus neutralization assay.

“Of note, we previously reported a correlation between neutralization titers obtained with the S-Fuse reporter assay and a pseudovirus neutralization assay 38 .”

• cites [38] Sterlin, D. et al. IgA dominates the early neutralizing antibody response to SARS-CoV-2. Sci. Transl. Med. https://doi.org/10.1126/scitranslmed.abd2223 (2020). sourceNot checked yet

  Not checked in the free run.

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

Lack of access to pre-vaccination nasal swabs precluded determination of whether previous infection, vaccination, or the combination generated a neutralizing response in these individuals.

“Unfortunately, we did not have access to their nasal swabs before vaccination, precluding determination of whether previous infection, vaccination or, more likely, the combination of both, generated a neutralizing response in these individuals.”

May combine two claims.

The Pfizer Cominarty vaccine generated a neutralizing response that efficiently targeted D614G and B.1.1.7, with a delay in the appearance of neutralizing antibodies to B.1.1.7 and B.1.351 relative to D614G.

“Therefore, the Pfizer Cominarty vaccine generated a neutralizing response that efficiently targeted D614G and B.1.1.7 with a delay in the appearance of neutralizing antibodies to B.1.1.7 and B.1.351relative to D614G.”

May combine two claims.

S proteins from B.1.351, and to a higher extent B.1.1.7, display increased affinity for ACE2 while escaping binding to some monoclonal antibodies and either to a lesser degree or not at all to polyclonal sera.

“Altogether, these results indicate that S proteins from B.1.351,and to a higher extent B.1.1.7,display increased affinity for ACE2 while escaping binding to some monoclonal antibodies and either to a lesser degree or not at all to polyclonal sera.”

• AssumptionRests on an assumption: The D614G, B.1.1.7, and B.1.351 S proteins expressed in cells were functional.

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

The S-Flow assay measures antibody binding to cells expressing the Wuhan S protein.

“we adapted the flow cytometry-based S-Flow assay, which we previously established to measure the levels of antibodies binding to cells expressing the Wuhan S protein 35 .”

• cites [35] Grzelak, L. et al. A comparison of four serological assays for detecting anti-SARS-CoV-2 antibodies in human serum samples from different populations. Sci. Transl. Med. https://doi.org/10.1126/scitranslmed.abc3103 (2020). sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Some vaccines may not protect against viral acquisition and infection of the oral-nasal region, but may prevent severe disease associated with viral dissemination in the lower respiratory tract.

“They strengthen the hypothesis that some vaccines may not protect against viral acquisition and infection of the oral-nasal region, but may prevent severe disease associated with viral dissemination in the lower respiratory tract.”

• cites [37] Dagotto, G., Yu, J. & Barouch, D. H. Approaches and challenges in SARS-CoV-2 vaccine development. Cell Host Microbe 28, 364–370 (2020). sourceNot checked yet

  Not checked in the free run.

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

The study's limitations include a relatively low number of individuals analyzed and a short time frame after vaccination.

“Potential limitations of our study are the relatively low number of individuals analyzed and the short time frame of analysis after vaccination.”

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

The funders of the study had no role in study design, data collection, analysis and interpretation, or writing of the article.

“The funders of this study had no role in study design, data collection, analysis and interpretation or writing of the article.”

Classified as probably not a substantial claim.

Using authentic clinical isolates provides a relevant way to assess inherent viral fitness and the impact of additional mutations outside S on sensitivity to neutralizing antibodies.

“Here, we used authentic clinical viral isolates, rather than pseudovirus, providing a relevant way to assess inherent viral fitness and the potential impact of additional mutations outside of S protein on sensitivity to neutralizing antibodies.”

• AssumptionRests on an assumption: Mutations outside the S protein may affect inherent viral fitness and/or sensitivity to antibodies.

May combine two claims.

The RBD mutation N501Y increases affinity to ACE2 and is present in B.1.1.7 and B.1.351, but does not impair post-vaccine serum neutralization on its own.

“The RBD mutation N501Y, which increases affinity to ACE2 and is present in B.1.1.7 and B.1.351(ref.20 ), does not impair on its own post-vaccine serum neutralization 21 .”

• cites [20] Zahradník, J. et al. SARS-CoV-2 RBD in vitro evolution follows contagious mutation spread, yet generates an able infection inhibitor. Preprint at BioRxiv https://doi.org/10.1101/2021.01.06.425392 (2021). sourceNot checked yet

  Not checked in the free run.

• cites [21] Xie, X. et al. Neutralization of SARS-CoV-2 spike 69/70 deletion, E484K and N501Y variants by BNT162b2 vaccine-elicited sera. Nat. Med. https://doi.org/10.1038/s41591-021-01270-4 (2021). sourceNot checked yet

  Not checked in the free run.

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

The Epitope Diagnostics ELISA for IgG against the full-length recombinant N protein has a specificity of 96% and a sensitivity of 81% after 28 days post-symptom onset.

“a CE-marked ELISA for detection of IgG against the full-length recombinant N protein from Epitope Diagnostics (EDITM Novel coronavirus COVID-19 IgG), which has a specificity of 96% and a sensitivity of 81% after 28 d POS”

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

The combination of S-Fuse and S-Flow assays allowed rapid assessment of viral infectivity, neutralization, and antibody levels for emerging variants.

“On a technical note, the combination of S-Fuse and S-Flow assays, two methods of analysis of viral infectivity, neutralization or antibody levels, allowed a rapid assessment of the properties of emerging variants.”

May combine two claims.

The S-Flow serological assay, assessed with the Wuhan S protein on 253 pre-pandemic samples and 377 RT-qPCR-confirmed SARS-CoV-2 samples, has a sensitivity of 99.2% (95% CI 97.69-99.78%) and a specificity of 100% (98.5-100%).

“The specificity and sensitivity of the S-Flow serological assay were originally assessed with the Wuhan S protein using 253 pre-pandemic samples and 377 RT-qPCR-confirmed SARS-CoV-2 samples.The sensitivity is 99.2% with a 95% confidence interval of 97.69-99.78%and the specificity is 100% (98.5-100%) 33,35 .”

• cites [33] Fafi-Kremer, S. et al. Serologic responses to SARS-CoV-2 infection among hospital staff with mild disease in eastern France. EBioMedicine https://doi.org/10.1016/j.ebiom.2020.102915 (2020). sourceNot checked yet

  Not checked in the free run.

• cites [35] Grzelak, L. et al. A comparison of four serological assays for detecting anti-SARS-CoV-2 antibodies in human serum samples from different populations. Sci. Transl. Med. https://doi.org/10.1126/scitranslmed.abc3103 (2020). sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S2 (checkable).

It is important to use authentic variant strains in addition to pseudovirus particles because mutations outside S may impact inherent viral fitness and/or sensitivity to antibodies.

“It is thus of utmost importance to use authentic variant strains in addition to pseudovirus particles, since mutations outside of the S protein may impact inherent viral fitness and/or sensitivity to antibodies.”

• AssumptionRests on an assumption: Mutations outside the S protein may affect inherent viral fitness and/or sensitivity to antibodies.

May combine two claims.

The D614G mutation enhances viral infectivity and shifts S protein conformation toward an ACE2-binding fusion-competent state without significantly modifying sensitivity to antibody neutralization.

“One of the first identified variants includes the D614G mutation in the gene encoding the spike (S) protein, which enhances viral infectivity and shifts S protein conformation toward an angiotensin-converting enzyme 2 (ACE2)-binding fusion-competent state, without significantly modifying sensitivity to antibody neutralization 1,[6][7][8] .”

• cites [1] Yurkovetskiy, L. et al. Structural and functional analysis of the D614G SARS-CoV-2 spike protein variant. Cell 183, 739–751 (2020). sourceNot checked yet

  Not checked in the free run.

• cites [6] Korber, B. et al. Tracking changes in SARS-CoV-2 spike: evidence that D614G increases infectivity of the COVID-19 virus. Cell 182, 812–827 (2020). sourceNot checked yet

  Not checked in the free run.

• cites [7] Plante, J. A. et al. Spike mutation D614G alters SARS-CoV-2 fitness. Nature https://doi.org/10.1038/s41586-020-2895-3 (2020). sourceNot checked yet

  Not checked in the free run.

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

The B.1.1.7 variant emerged in the United Kingdom, B.1.351 in South Africa, and P.1 and P.2 lineages in Brazil.

“The B.1.1.7 variant emerged in the United Kingdom, the B.1.351variant (also termed 501Y.V2) in South Africa and the P.1 and P.2 lineages in Brazil 2,3,5,9-12 .”

• cites [2] Kemp, S. et al. Recurrent emergence and transmission of a SARS-CoV-2 spike deletion ΔH69/V70. Preprint at BioRxiv https://doi.org/10.1101/2020.12.14.422555 (2020). sourceNot checked yet

  Not checked in the free run.

• cites [3] Kemp, S. A. et al. SARS-CoV-2 evolution during treatment of chronic infection. Nature https://doi.org/10.1038/s41586-021-03291-y (2021). sourceNot checked yet

  Not checked in the free run.

• cites [5] Tegally, H. et al. Emergence of a SARS-CoV-2 variant of concern with mutations in spike glycoprotein. Nature https://doi.org/10.1038/s41586-021-03402-9 (2021). sourceNot checked yet

  Not checked in the free run.

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

The study did not investigate the impact of preexisting cellular immunity, which may be more cross-reactive against variants than the humoral response.

“Furthermore, we have not investigated the impact of preexisting cellular immunity, which may be more cross-reactive against variants than the humoral response.”

Classified as probably not a substantial claim.

The positivity threshold of the S-Flow assay was defined as specific binding above 40%, determined after testing 253 pre-pandemic samples.

“After testing 253 pre-pandemic samples, the positivity of a sample was defined as a specific binding above 40%.”

• cites [33] Fafi-Kremer, S. et al. Serologic responses to SARS-CoV-2 infection among hospital staff with mild disease in eastern France. EBioMedicine https://doi.org/10.1016/j.ebiom.2020.102915 (2020). sourceNot checked yet

  Not checked in the free run.

• cites [35] Grzelak, L. et al. A comparison of four serological assays for detecting anti-SARS-CoV-2 antibodies in human serum samples from different populations. Sci. Transl. Med. https://doi.org/10.1126/scitranslmed.abc3103 (2020). sourceNot checked yet

  Not checked in the free run.

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

The experiments were not randomized and the investigators were not blinded to allocation during experiments and outcome assessment.

“The experiments were not randomized and the investigators were not blinded to allocation during experiments and outcome assessment.”

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

No statistical methods were used to predetermine the sample size.

“No statistical methods were used to predetermine sample size.”

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

The Biosynex COVID-19 BSS IgG/IgM LFA assay has a specificity of 99% and a sensitivity of 96% for samples more than 22 days post-symptom onset.

“a CE-marked LFA assay for detection of IgM and IgG against the SARS-CoV-2 RBD of the S protein developed by Biosynex (COVID-19 BSS IgG/IgM), which has a specificity of 99% and a sensitivity of 96% for samples >22 d POS”