Reduced neutralization of SARS-CoV-2 B.1.617 by vaccine and convalescent serum

May combine two claims.

For B.1.617.1, 8 mAbs (58, 88, 170, 278, 281, 316, 384, and 398) showed a more than 5-fold reduction in neutralization titers, with most showing almost complete knockout of activity.

“For B.1.617.1, 8 mAbs (58, 88, 170, 278, 281, 316, 384, and 398) showed a more than 5-fold reduction in neutralization titers, with most of these showing almost complete knockout of activity (Figure 2A; Table S1).”

May combine two claims.

Neutralization of B.1.617.2 was reduced more than 5-fold for 6 antibodies, and neutralization by NTD mAb 159 was lost completely.

“Neutralization of B.1.617.2 was reduced more than 5-fold for 6 antibodies, neutralization by NTD mAb 159 was lost completely, and neutralization by mAbs 58, 170, 278, 281, and 384 was reduced in common with neutralization of B.1.617.1”

May combine two claims.

LY-CoV555 completely failed to neutralize B.1.617.1 and was reduced severely on B.1.617.2.

“The exceptions were LY-CoV555, which completely failed to neutralize B.1.617.1 and was reduced severely on B.1.617.2 (Greaney et al., 2021), and for unknown reasons, S309 (Pinto et al., 2020) could not neutralize the Victoria pseudotyped virus, so we could not reliably compare its activity on B.1.617.1.”

May combine two claims.

The most affected antibodies are especially in the top and front in the neck epitope, with a small effect on some antibodies belonging to the right flank epitope.

“The most affected antibodies are especially in the top and front in the neck epitope (nomenclature of Dejnirattisai et al., 2021a), with a small effect on some antibodies belonging to the right flank epitope.”

May combine two claims.

Structures of antibodies such as 384 show reliance on contacts with L452 and E484, with E484 contacts probably dominant to L452.

“structures of other antibodies, such as 384, demonstrate reliance on contacts with L452 and E484, with the contacts with E484 probably dominant to L452 (Figure 4L).”

May combine two claims.

The structure of mAb 316 shows contact with E484 but no contact with L452.

“the structure of mAb 316 shows contact with E484 but no contact with L452 (Figure 4J).”

May combine two claims.

Fab 253 is the only antibody whose binding is perturbed significantly by the mutation at RBD residue 478, and the mutation to lysine increases the neutralization titer by approximately one log.

“Fab 253 is the only antibody whose binding is perturbed significantly by the mutation at RBD residue 478 (the closely related mAb 55 shows a similar but reduced effect), and the mutation to lysine actually increases the neutralization titer by approximately one log.”

May combine two claims.

There are significant reductions in neutralization titers of sera from recipients of the Oxford-AstraZeneca and Pfizer-BioNTech vaccines against B.1.617.1 and B.1.617.2, but no evidence of widespread complete escape from neutralization.

“There are also significant reductions in neutralization titers of sera collected from recipients of the Oxford-AstraZeneca and Pfizer-BioNTech vaccines but no evidence of widespread complete escape from neutralization.”

May combine two claims.

Peak neutralization at 1/20 serum dilution averaged 63% and 47% for Victoria and 27% and 7% for B.1.617.2 at 4 and 10 weeks after one Pfizer-BioNTech dose.

“Peak neutralization titers at serum dilution of 1/20 were an average of 63% and 47% for Victoria and 27% and 7% for B.1.617.2 at 4 and 10 weeks, respectively”

May combine two claims.

The structure confirms that the effect on Fab 253 is due to direct interaction with RBD residue 478, with the lysine side chain in the variant RBD folding away behind the CDR1 loop of the light chain.

“Perhaps surprisingly, this is the only example we have come across of a marked increase in binding to a variant virus, and the structure confirms that this effect is due to direct interaction with RBD residue 478, with the lysine side chain in the variant RBD folding away behind the CDR1 loop of the light chain (LC) (Figures 4I and 4J).”

May combine two claims.

The structure confirms that neither RBD residue 478 nor 484 contact the antibody and that binding abrogation is mediated by direct contact between the 16-residue-long heavy chain CDR3 and RBD residue 452, which could not accommodate the major increase in side-chain size in going from leucine to arginine.

“The structure confirms that neither RBD residue 478 nor 484 contact the antibody and that binding abrogation is mediated by direct contact between the 16-residue-long heavy chain (HC) complementarity determining region (CDR) 3 and RBD residue 452, which could not accommodate the major increase in side-chain size in going from leucine to arginine in the variant viruses (Figure 4C).”

May combine two claims.

Following one dose of vaccine, titers against B.1.617.2 were lower, with FRNT ≥ 50% in 4 of 20 individuals at 4 weeks and 0 of 20 individuals at 10 weeks.

“Titers against B.1.617.2 were lower, with FRNT ≥ 50% in 4 of 20 individuals at 4 weeks and 0 of 20 individuals at 10 weeks (Figures 7E and 7F).”

• Also stated in: § Discussion · plain

  “we find that, following a single dose of the Pfizer-BioNTech vaccine, neutralization of B.1.617.2 is limited.”

May combine two claims.

Both B.1.617.1 and B.1.617.2 show partial or complete escape from neutralization by some monoclonal antibodies, but neutralization of most monoclonal antibodies is unaffected.

“Using a panel of potent neutralizing antibodies, we show that both viruses show partial or complete escape from neutralization by some antibodies but that neutralization of most monoclonal antibodies is unaffected.”

May combine two claims.

In many cases, neutralization of B.1.617.2 by B.1.351 and P.1 serum is lost almost completely, most profoundly for P.1.

“Inspection of the neutralization curves using B.1.351 and P.1 serum (Figures 6E and 6F) shows that, in many cases, neutralization is lost almost completely to B.1.617.2, most profoundly for P.1, suggesting that individuals infected with B.1.351 and P.1 may be at risk of reinfection with B.1.617.2.”

May combine two claims.

Following one dose of vaccine, neutralization of Victoria was observed in most individuals, with FRNT ≥ 50% in 16 of 20 individuals at 4 weeks and 9 of 20 individuals at 10 weeks.

“Following one dose of the vaccine, neutralization of Victoria was observed in most individuals, with FRNT ≥ 50% in 16 of 20 individuals at 4 weeks and 9 of 20 individuals at 10 weeks.”

May combine two claims.

Reductions in neutralization were comparable in scale with those seen with B.1.1.7 and P.1, with no evidence of widespread escape from neutralization, in contrast to B.1.351.

“Reductions were comparable in scale with those seen with B.1.1.7 and P.1, with no evidence of widespread escape from neutralization, in contrast to that seen with B.1.351.”

May combine two claims.

Compared with Victoria, neutralization titers to B.1.617.2 were reduced for B.1.1.7 serum 2.8-fold (p = 0.0003), for B.1.351 serum 6.0-fold (p < 0.0001), and for P.1 serum 2.9-fold (p = 0.0005).

“Compared with Victoria, neutralization titers to B.1.617.2 were reduced for B.1.1.7 serum 2.8-fold (p = 0.0003), for B.1.351 serum 6.0-fold (p < 0.0001), and for P.1 serum 2.9-fold (p = 0.0005) (Figures 6B–6D; Table S3).”

May combine two claims.

Antibody 316 contacts the B.1.617.1-specific mutation E484 but not RBD residues L452 or T478.

“Finally, by reference to structures we have determined previously, we can confirm that antibody 316, which only loses neutralization of B.1.617.1, contacts the B.1.617.1-specific mutation E484 but not RBD residues L452 or T478 (Figures 4K and 4L).”

May combine two claims.

REGN10987 and mAb 75 bind at a similar site as mAb 278, and all three antibodies overlap the ACE2 binding site, but neither REGN10987 nor mAb 75 directly contact RBD residue 452.

“Although REGN10987 and mAb 75 bind at a similar site as mAb 278, and all three antibodies overlap the ACE2 binding site (Baum et al., 2020; Dejnirattisai et al., 2021a), the engagement is sufficiently different that neither REGN10987 nor mAb 75 directly contact RBD residue 452 (Figure S2).”

May combine two claims.

REGN10987 is effective against B.1.617.1 and B.1.617.2, whereas mAb 75 is a weak binder.

“REGN10987 is effective against B.1.617.1 and B.1.617.2, whereas mAb 75 is a weak binder.”

May combine two claims.

The light chain of mAb 253 contacts RBD residue T478, and the change at 478 enhances binding/neutralization of B.1.617.2.

“The light chain of mAb 253 contacts RBD residue T478, and the change at 478 enhances the binding/neutralization of B.1.617.2 (Figures 4G and 4H).”

May combine two claims.

For B.1.1.7 serum, neutralization of B.1.617.2 was reduced 1.5-fold (p = 0.4038) compared with B.1.1.7; for B.1.351 serum, neutralization was reduced 11.6-fold (p = 0.0001) compared with B.1.351; and for P.1 serum, it was reduced 11.3-fold (p < 0.0001) compared with P.1.

“For B.1.1.7 serum, neutralization of B.1.617.2 was reduced 1.5-fold (p = 0.4038) compared with B.1.1.7.; for B.1.351, serum neutralization was reduced 11.6-fold (p = 0.0001) compared with B.1.351; and for P.1, it was reduced 11.3-fold (p < 0.0001) compared with P.1 (Figures 6B–6D).”

May combine two claims.

Neutralization of B.1.617.1 and B.1.617.2 by convalescent and vaccine sera is reduced compared with ancestral Wuhan-related strains, with 4-fold and 2.7-fold reductions for convalescent plasma to B.1.617.1 and B.1.617.2, respectively.

“Neutralization of both viruses is reduced compared with ancestral Wuhan-related strains, but there is no evidence of widespread antibody escape as seen with B.1.351.”

• Also stated in: § Introduction · plain

  “Neutralization by a panel of plasma collected from convalescent individuals from the United Kingdom early in the pandemic show 4-fold and 2.7-fold reduction in neutralization titers to B.1.617.1 and B.1.617.2, respectively, compared with an early Wuhan-related strain.”

May combine two claims.

The RBD L452R mutation introduces no significant change in the RBD structure and residue 452 does not directly contact Fab 253.

“The RBD 452 mutation had no effect on neutralization or binding of mAb 253, and the structure confirms that the RBD L452R mutation introduces no significant change in the RBD structure and that residue 452 does not directly contact Fab 253 (Figure 4G).”

May combine two claims.

Clustering variants by antigenic distance gives completely different results from clustering by lineage, reflecting the major effect of a small number of mutations that switch electrostatic properties around the ACE2 binding footprint.

“One striking outcome of this analysis is that clustering variants on the basis of antigenic distance gives completely different results from clustering by lineage, reflecting the major effect of a small number of mutations, which almost entirely switch the electrostatic properties by introducing basic residues around the edge of the ACE2 binding footprint on the RBD (Figure 7J).”

• AssumptionRests on an assumption: The antigenic map derived from available serum/virus strain pairs accurately represents antigenic relationships among SARS-CoV-2 variants.

May combine two claims.

Relative to Victoria, geometric mean neutralization titers of early UK convalescent plasma were reduced 2.5-fold (p = 0.0002) for B.1.617-A, 3.9-fold (p < 0.0001) for B.1.617.1-B, and 1.5-fold (p = 0.0248) for B.1.617-C.

“Relative to Victoria, geometric mean neutralization titers were reduced 2.5-fold (p = 0.0002) for B.1.617-A, 3.9-fold (p < 0.0001) for B.1.617.1-B, and 1.5-fold (p = 0.0248) for B.1.617-C.”

May combine two claims.

Neutralization of B.1.617.1-B compared with Victoria by sera from individuals infected with B.1.1.7 was reduced 4.3-fold (p < 0.0001), by B.1.351 sera 1.8-fold (p = 0.0833), and by P.1 sera 2.1-fold (p = 0.0026).

“Next we measured neutralization of B.1.617.1-B compared with Victoria by sera taken from individuals infected with B.1.1.7 (4.3-fold reduction [p < 0.0001]), B.1.351 (1.8-fold reduction [p = 0.0833]), and P.1 (2.1-fold reduction [p = 0.0026]), indicating that infection with these variant viruses provides substantial cross-protection against B.1.617.1, with no samples showing complete escape from”

May combine two claims.

Neutralization of B.1.617.2 was completely absent in 4 of 14 sera from people previously infected with B.1.351 and 10 of 17 sera from people previously infected with P.1.

“Of more concern was neutralization of B.1.617.2 by sera from people infected previously with B.1.351 and P.1, with 4 of 14 and 10 of 17 showing complete absence of neutralization of B.1.617.2, respectively.”

May combine two claims.

In antigenic space, the largest distance is between the B.1.351/P.1 lineages and B.1.617.2, whereas B.1.617.1 is significantly closer to B.1.351/P.1.

“that the largest distance is between the B.1.351/P.1 lineages and B.1.617.2, whereas B.1.617.1 is significantly closer to B.1.351/P.1.”

• AssumptionRests on an assumption: The antigenic map derived from available serum/virus strain pairs accurately represents antigenic relationships among SARS-CoV-2 variants.

May combine two claims.

In antigenic space, B.1.351 is roughly orthogonal to B.1.617.2, and P.1 is essentially opposite (anticorrelated with) B.1.617.2.

“Although B.1.351 is roughly orthogonal to B.1.617.2, P.1 is essentially opposite (anticorrelated with) B.1.617.2”

• AssumptionRests on an assumption: The antigenic map derived from available serum/virus strain pairs accurately represents antigenic relationships among SARS-CoV-2 variants.

May combine two claims.

Only a small number of samples failed to reach FRNT50 titers at 1:20 serum dilution for B.1.617.2, in contrast to B.1.351.

“with only a small number of samples failing to reach FRNT50 titers at 1:20 serum dilution, in contrast to the results seen for neutralization of B.1.351 (Figure S4).”

May combine two claims.

Of the 13 different Fab complexes for which structures exist, only mAb 278 makes strong contacts with RBD residue 452; mAb 384 makes weak contacts with RBD residue 452 but more important contacts with residue 484.

“In fact, of the 13 different Fab complexes for which we have structures, only mAb 278 makes strong contacts with RBD residue 452; however, in addition, mAb 384 makes weak contacts with RBD residue 452 (Figures 4E and 4F) but more important contacts with residue 484.”

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

In the antigenic space analysis, the largest axis of variation was largely identical for each strain, representing the positivity in common with all log dilution values.

“The largest axis of variation was largely identical for each strain, representing the positivity in common with all log dilution values.”

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

Progressive mutational change in SARS-CoV-2 is inevitable as it undergoes massive numbers of replicative cycles worldwide.

“Progressive mutational change in the virus is therefore inevitable as it undergoes massive numbers of replicative cycles worldwide (Tegally et al., 2021).”

• cites Tegally et al., 2021 sourceNot checked yet

  Not checked in the free run.

Classified as probably not a substantial claim.

Mutations in SARS-CoV-2 could confer advantage by increased transmissibility or escape from innate or acquired immune responses.

“Mutations could confer advantage to the virus in a number of ways, but increased transmissibility or escape from innate or acquired immune responses are two potential examples (Volz et al., 2021).”

• cites Volz et al., 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.

Some mutations in SARS-CoV-2 will be advantageous and subject to rapid natural selection.

“although most will be detrimental or confer no advantage to the virus, some will be advantageous and be the subject of rapid natural selection (Domingo et al., 2012; Rambaut et al., 2020).”

• cites Domingo et al., 2012 sourceNot checked yet

  Not checked in the free run.

• cites Rambaut et al., 2020Not checked yet

  Not checked in the free run.

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

Several studies have shown reduced vaccine efficacy against mild to moderate COVID-19 in countries where B.1.351 was dominant, although protection against severe disease appears preserved.

“Several studies have now shown that there is reduced vaccine efficacy against mild to moderate disease in countries where B1.351 was dominant (Zhou et al., 2021; Shinde et al., 2021; Madhi et al., 2021, Vaccines and Related Biological Products Advisory Committee, 2021), although protection against severe disease appears to be preserved.”

• cites Zhou et al., 2021 sourceNot checked yet

  Not checked in the free run.

• cites Shinde et al., 2021 sourceNot checked yet

  Not checked in the free run.

• cites Madhi et al., 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.

L452R has also been identified in B.1.427 and B.1.429, and T478K is found in B.1.1.519.

“L452R has also been identified in B.1.427 and B.1.429 (Deng et al., 2021), and T478K is found in B.1.1.519.”

• cites Deng et al., 2021 sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Neutralization by mAbs 58, 170, 278, 281, and 384 was reduced in common with neutralization of B.1.617.1, suggesting that these antibodies may share an epitope overlapping the RBD L452R substitution.

“Neutralization of B.1.617.2 was reduced more than 5-fold for 6 antibodies, neutralization by NTD mAb 159 was lost completely, and neutralization by mAbs 58, 170, 278, 281, and 384 was reduced in common with neutralization of B.1.617.1, suggesting that these antibodies may share an epitope overlapping the RBD L452R substitution.”

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

B.1.617.2 shares L452R and P681R with B.1.617.1, and 20% of reported sequences share T95I.

“B.1.617.2 shares L452R and P681R with B.1.617.1, and 20% of reported sequences share T95I.”

May combine two claims.

The ACE2-interacting surface of SARS-CoV-2 S is under intense selective pressure because changes may increase ACE2/RBD affinity, potentially increasing transmissibility, while also reducing antibody binding and neutralizing potential.

“The ACE2-interacting surface of S is under intense selective pressure because changes may increase ACE2/RBD affinity, potentially increasing virus transmissibility, whereas the same changes may also reduce antibody binding to the RBD, decreasing the neutralizing potential of immune serum.”

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

The neutralizing titers of convalescent and vaccine sera are reduced to B.1.351, leading to a 13-fold reduction in neutralizing titers of convalescent serum, with a number of neutralizing mAbs losing activity completely.

“The neutralizing titers of convalescent and vaccine sera are reduced to the variants with B.1.351 of most concern, leading to a 13-fold reduction in neutralizing titers of convalescent serum, with a number of neutralizing monoclonal antibodies losing activity completely (Zhou et al., 2021; Supasa et al., 2021; Dejnirattisai et al., 2021b; Shinde et al., 2021; Madhi et al., 2021; Food and Drug Adm”

• cites Zhou et al., 2021 sourceNot checked yet

  Not checked in the free run.

• cites Supasa et al., 2021 sourceNot checked yet

  Not checked in the free run.

• cites Dejnirattisai et al., 2021bNot checked yet

  Not checked in the free run.

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

The RBD and especially the NTD of SARS-CoV-2 S are mutational hotspots.

“Many mutations in S have been reported, and it appears that the RBD and especially the NTD are mutational hotspots (Greaney et al., 2021).”

• cites Greaney et al., 2021 sourceNot checked yet

  Not checked in the free run.

May combine two claims.

B.1.1.519 (T478K) has a similar KD (33 nM) to Victoria RBD, suggesting that L452R does not significantly alter affinity for ACE2.

“B.1.1.519 (T478K) has a similar KD (33 nM), suggesting that L452R does not significantly alter affinity for ACE2.”

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

Lessening of the charge difference in RBD residue Q484K versus E484K and less pronounced NTD differences may make B.1.617.1 less resistant to neutralization by B.1.351 and P.1 serum.

“it may be that lessening of the charge difference in RBD residue Q484K versus E484K and less pronounced differences in the NTDs make B.1.617.1 less resistant to neutralization by B.1.351 and P.1 serum.”

May combine two claims.

In the set of 20 potent neutralizers, interaction with RBD residue 452 was inferred from neutralization and binding data for three further mAbs (58, 170, and 281) for which structures are not available, but competition mapping positioning is consistent with contact.

“However, McCallum et al. (2021) report several RBD residue 452-interacting antibodies, and in our set of 20 potent neutralizers, we inferred interaction from the neutralization and binding data for three further mAbs (58, 170, and 281) for which we do not have structures, but competition mapping positioning is consistent with contact (Figure 3B; Dejnirattisai et al., 2021a), suggesting that such”

• cites McCallum et al., 2021Not checked yet

  Not checked in the free run.

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

Changes in the S protein likely underpin some phenotypes expressed by variants of concern.

“it is no surprise that it is evolving rapidly and that changes in S likely underpin some of the phenotypes expressed by variants of concern.”

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

Plasma/serum samples were heat inactivated and aliquoted so that no more than 3 freeze-thaw cycles were performed for data generation.

“Following heat inactivation of plasma/serum samples they were aliquoted so that no more than 3 freeze thaw cycles were performed for data generation.”

May combine two claims.

Differences in neutralization of the three B.1.617.1 subtypes may be due to mutations occurring in the NTD: 0 in B.1.617.1-C, 1 in B.1.617.1-A, and 3 in B.1.617-B, which was the most difficult to neutralize.

“Differences in neutralization of three different B.1.617.1 subtypes may be due to mutations occurring in the NTD: 0 in B.1.617.1-C, 1 in B.1.617.1-A, and 3 in B.1.617-B, which was the most difficult to neutralize.”

May combine two claims.

Serum from donors infected with B.1.1.7 appears to give good protection against all variants of concern, whereas protection from B.1.617.2 afforded by previous infection with B.1.351 and P.1 is much more compromised.

“Serum from donors infected with B.1.1.7 appears to give good protection against all variants of concern, whereas protection from B.1.617.2 afforded by previous infection with B.1.351 and P.1 is much more compromised.”

• AssumptionRests on an assumption: In vitro neutralization titers predict protection against infection or reinfection in vivo.

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

Viral stocks were sequenced to verify expected spike protein sequence and no changes to furin cleavage sites.

“Victoria passage 5, B.1.1.7 passage 2 and B.1.351 passage 4 stocks P.1 passage 1 stocks were sequenced to verify that they contained the expected spike protein sequence and no changes to the furin cleavage sites.”

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

The disparity in neutralization of B.1.617.2 by B.1.351 and P.1 serum may be explained by additive differences between the viruses.

“An explanation for the disparity in neutralization of B.1.617.2 by B.1.351 and P.1 serum may be that the differences between the two viruses are additive.”

The quote only partly states this claim.

The especially poor ability of P.1 serum to neutralize B.1.617.2 is reflected in the antigenic map.

“reflecting the especially poor ability of P.1 serum to neutralize B.1.67.2.”

• AssumptionRests on an assumption: The antigenic map derived from available serum/virus strain pairs accurately represents antigenic relationships among SARS-CoV-2 variants.

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

Previous studies have shown protection following a single dose of vaccine despite low or absent antibody responses.

“Previous studies have shown protection following a single dose of vaccine despite low or absent antibody responses”

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

As population immunity develops, selection pressure is mounting for mutations that increase transmissibility or evade acquired immunity and cause reinfection.

“As the population develops immunity by natural infection or vaccination, pressure is mounting to select mutations that allow the virus to more effectively find an infectible host through increased transmissibility or evade the acquired immune response and cause reinfection.”

May combine two claims.

The assays do not measure the T cell response, which may contribute to protection from severe disease and appears less disrupted by variant changes.

“Assays do not measure the T cell response, which may contribute to protection from severe disease and appear to be less disrupted by the changes in the variants of concern (Skelly et al., 2021).”

• cites Skelly et al., 2021Not checked yet

  Not checked in the free run.

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

The sample with extremely high titers was excluded from the statistical analysis for B.1.1.7 data.

“For the data presented for B.1.1.7 in (B), the sample with extremely high titers was excluded from the statistical analysis.”

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

B.1.351 samples from UK infected cases were collected under a protocol approved by the University of Oxford Central University Research Ethics Committee.

“B.1.351 samples from UK infected cases was collected under the “Innate and adaptive immunity against SARS-CoV-2 in healthcare worker family and household members” protocol affiliated to the Gastro-intestinal illness in Oxford: COVID sub study discussed above and approved by the University of Oxford Central University Research Ethics Committee.”

May combine two claims.

Neutralization and binding of mAb 278 are affected for B.1.617.1 and B.1.617.2, and the mutation of RBD residue 452 was responsible.

“Neutralization and binding of mAb 278 are affected for B.1.617.1 and B.1.617.2, and we inferred that the mutation of RBD residue 452 was responsible.”

May combine two claims.

The in vitro neutralization assays were performed in the absence of complement or Fc receptor-bearing cells, which may cause them to underestimate protection of immune serum.

“The in vitro neutralization assays described here are performed in the absence of complement or Fc receptor-bearing cells, which can mediate antibody-dependent cell-mediated cytotoxicity, meaning they may underestimate the protection of immune serum.”

Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing). May combine two claims.

It is likely that the true scale of SARS-CoV-2 diversity is underestimated and that further concerning variants are circulating and will continue to arise.

“It is likely that the true scale of the diversity in SARS-CoV-2 is underestimated and that further concerning variants are circulating and will continue to arise.”

May combine two claims.

It is likely that current RNA and viral vector vaccines will provide protection against the B.1.617 lineage, although reduced neutralizing capacity may lead to some breakthrough infections.

“It would seem likely from these results that the current RNA and viral vector vaccines will provide protection against the B.1.617 lineage, although an increase in breakthrough infections may occur as a result of the reduced neutralizing capacity of sera.”

• Also stated in: § Discussion · hedged

  “Although there is a reduction in neutralization titers using convalescent or vaccine sera there is no evidence of widespread escape, suggesting that the current generation of vaccines will provide protection against the B.1.617 lineage, although reduced titers may lead to some breakthrough infections.”

• AssumptionRests on an assumption: Neutralizing antibody titers are a reliable correlate of protection against SARS-CoV-2 infection and disease.
• AssumptionRests on an assumption: In vitro neutralization results predict protection from infection or reinfection in vivo.

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

The Pfizer vaccine study was conducted according to the principles of the Declaration of Helsinki (2008).

“The study was conducted according to the principles of the Declaration of Helsinki (2008) and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines.”

Probably not a substantial claim: may not pass S3 (load-bearing). The quote only partly states this claim.

All constructs of ACE2 and RBD proteins were verified by sequencing.

“All constructs were verified by sequencing.”

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

The AstraZeneca-Oxford vaccine studies were registered at ISRCTN (15281137 and 89951424) and ClinicalTrials.gov (NCT04324606 and NCT04400838).

“These studies were registered at ISRCTN (15281137 and 89951424) and ClinicalTrials.gov (NCT04324606 and NCT04400838).”

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

All individuals with B.1.351 samples had sequence-confirmed B.1.351 infection or PCR-confirmed symptomatic disease occurring while in isolation and in direct contact with B.1.351 sequence-confirmed cases.

“All individuals had sequence confirmed B.1.351 infection or PCR-confirmed symptomatic disease occurring while in isolation and in direct contact with B.1.351 sequence-confirmed cases.”

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

All constructs of pseudotyped lentivirus expressing SARS-CoV-2 S proteins were verified by Sanger sequencing.

“All constructs were verified by Sanger sequencing.”

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

Vaccinees were Health Care Workers based at Oxford University Hospitals NHS Foundation Trust, not known to have prior infection with SARS-CoV-2.

“Vaccinees were Health Care Workers, based at Oxford University Hospitals NHS Foundation Trust, not known to have prior infection with SARS-CoV-2 and were enrolled in the OPTIC Study as part of the Oxford Translational Gastrointestinal Unit GI Biobank Study 16/YH/0247 [research ethics committee (REC) at Yorkshire & The Humber – Sheffield].”

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

The Pfizer vaccine study was conducted according to the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines.

“The study was conducted according to the principles of the Declaration of Helsinki (2008) and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines.”

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

In each experiment, 90 ng/mL of HIV-gag protein was normalized using the RETROtek HIV-1 p24 Antigen-ELISA kit.

“In each experiment, 90 ng/mL of HIV- gag protein was normalized using the RETROtek HIV-1 p24 Antigen-ELISA kit (Zeptometrix; Buffalo, NY), according to manufacturer’s instructions.”

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

The AstraZeneca-Oxford vaccine trial is being done in accordance with the principles of the Declaration of Helsinki.

“Written informed consent was obtained from all participants, and the trial is being done in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice.”

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

The study was approved by the Human Research Ethics Committee of the University of the Witwatersrand (reference number 200313).

“The study was approved by the Human Research Ethics Committee of the University of the Witwatersrand (reference number 200313) and conducted in accordance with Good Clinical Practice guidelines.”

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

Approval was obtained from a national ethics committee (South Central Berkshire Research Ethics Committee, reference 20/SC/0145 and 20/SC/0179).

“The studies were sponsored by the University of Oxford (Oxford, UK) and approval obtained from a national ethics committee (South Central Berkshire Research Ethics Committee, reference 20/SC/0145 and 20/SC/0179) and a regulatory agency in the United Kingdom (the Medicines and Healthcare Products Regulatory Agency).”

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

An independent DSMB reviewed all interim safety reports.

“An independent DSMB reviewed all interim safety reports.”

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

Additional B.1.351 infected serum was sequence confirmed and was obtained from South Africa.

“Additional B.1.351 infected serum (sequence confirmed) was obtained from South Africa.”

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

The AstraZeneca-Oxford vaccine trial is being done in accordance with Good Clinical Practice.

“Written informed consent was obtained from all participants, and the trial is being done in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice.”

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

The study was conducted in accordance with Good Clinical Practice guidelines.

“The study was approved by the Human Research Ethics Committee of the University of the Witwatersrand (reference number 200313) and conducted in accordance with Good Clinical Practice guidelines.”

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

At the time of swab collection, patients signed an informed consent for the collection of data and serial blood samples.

“At the time of swab collection patients signed an informed consent to consent for the collection of data and serial blood samples.”

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

Written informed consent was obtained for all participants enrolled in the Pfizer vaccine study.

“Written informed consent was obtained for all participants enrolled in the study.”

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

Written informed consent was obtained from all participants in the AstraZeneca-Oxford vaccine studies.

“Written informed consent was obtained from all participants, and the trial is being done in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice.”

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

P.1 samples had the approval of the FIOCRUZ ethical committee (CEP 4.128.241) to continuously receive and analyze samples of COVID-19 suspected cases for virological surveillance.

“P.1 samples were provided by the International Reference Laboratory for Coronavirus at FIOCRUZ (WHO) as part of the national surveillance for coronavirus and had the approval of the FIOCRUZ ethical committee (CEP 4.128.241) to continuously receive and analyze samples of COVID-19 suspected cases for virological surveillance.”

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

Clones with >80% hACE2 positive cells were used as the target cells for pseudotyped based neutralization assays.

“The transduced cells were subjected to hACE2 staining and single cell sorting, clones with > 80% hACE2 positive cells were used as the target cells for pseudotyped based neutralization assays.”

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

Approval was obtained from a regulatory agency in the United Kingdom (the Medicines and Healthcare Products Regulatory Agency).

“The studies were sponsored by the University of Oxford (Oxford, UK) and approval obtained from a national ethics committee (South Central Berkshire Research Ethics Committee, reference 20/SC/0145 and 20/SC/0179) and a regulatory agency in the United Kingdom (the Medicines and Healthcare Products Regulatory Agency).”