Fig. 6: In the Latin America cohort, N-terminal ___domain (NTD) sequence feature sieve analysis and visualization of defining sites in the NTD features that impacted vaccine efficacy (VE).
From: Quantifying how single dose Ad26.COV2.S vaccine efficacy depends on Spike sequence features
a VE estimates against the primary COVID-19 endpoint caused by SARS-CoV-2 with (vs. without) a NTD feature value, screened in as a specific hypothesis-driven neutralizing antibody (nAb) correlate of protection. VE estimates against SARS-CoV-2 harboring the NTD feature value are shown in blue; those against SARS-CoV-2 without the NTD feature value are shown in maroon. The solid squares represent the VE point estimates, and the error bars display the 95% confidence intervals. The “two-sided P value” is from testing the null hypothesis HAj0 vs. HAj2 using the test statistic U2j (pp 17–18 of Heng et al.18.) and the “two-sided differential VE P value” is from testing the null hypothesis HB0 vs. HB2 using the test statistic T2 (pp 18–19 of Heng et al.18.). b–e Visualization of the constituent mutation sites that define the NTD feature, for each NTD features that significantly impacted VE with an FWER p < 0.05 (NTD1, NTD3, NTD5, and NTD7) (PDB 7L2C). b NTD1: Cyan colors the two insertions or deletions regions with one common residue for deletion (Y144) shown. c NTD3: The four specific mutations are labeled and colored cyan or red based on being mutations of interest or not respectively. d NTD5: Cyan colors the two substitution regions highlighting the two exclusions that are both found in this structure. e NTD7: Pink colors all asparagine residues that form N-linked glycans with the corresponding carbohydrate colored by atom (C: cyan, N: blue, O: red). Each structure shows the entire NTD region and colors all non-highlighted portions gray. CI confidence interval, FWER family-wise error rate, PYRs person-years.
