Table 1. Description of WCV antigenic proteins, represented by probes associated with significantly increased IgG binding following WCV administration by either the empirical Bayes or linear mixed effects analyses (Supplementary file 2).
Each protein is listed (either by common name, or COG assignation), alongside a functional annotation and the coding sequence for the orthologue in S. pneumoniae D39, where it could be identified. IgG-binding values were aggregated across all probes corresponding to the named protein that were associated with a significant change. Values are summarised as a median, with the interquartile range in parentheses. The columns show the median initial IgG binding to the probes across all cohorts, and the Δ0→84 values for each of the four cohorts separately. The final column identifies in which analyses the set of probes corresponding to the named protein were found to be associated with elevated IgG binding.
| Protein name | Functional annotation | S. pneumoniae D39 coding sequence | IgG binding at day 0 | Δ0->84 in placebo group | Δ0->84 in cohort 1 | Δ0->84 in cohort 2 | Δ0->84 in cohort 3 | Statistical analysis |
|---|---|---|---|---|---|---|---|---|
| AatB | Amino acid ABC transporter solute-binding protein AatB | SPD_1328 | 3.568 (2.920–4.247) | −0.078 (−0.126–0.105) | 0.105 (−0.004–0.204) | 0.096 (0.076–0.214) | 0.285 (0.155–0.747) | Both |
| AcoC | Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex AcoC | SPD_1026 | 0.722 (0.381–1.346) | −0.149 (−0.180 - −0.053) | 0.021 (−0.049–0.475) | −0.003 (−0.062–0.019) | 0.463 (0.252–0.936) | Both |
| AliA | ABC oligopeptide transporter solute-binding protein AliA | SPD_0334 | 2.803 (2.141–3.679) | −0.085 (−0.149 - −0.008) | 0.042 (−0.076–0.086) | 0.203 (0.060–0.693) | 0.323 (0.179–0.576) | Both |
| AliB | Oligopeptide ABC transporter solute-binding protein AliB | SPD_1357 | 4.098 (3.457–4.553) | −0.018 (−0.111–0.094) | 0.142 (0.038–0.229) | 0.159 (0.015–0.305) | 0.159 (0.082–0.242) | Linear mixed effects |
| AmiA | Oligopeptide ABC transporter solute-binding protein AmiA | SPD_1671 | 3.680 (2.954–4.122) | −0.007 (−0.073–0.079) | 0.216 (0.068–0.489) | 0.343 (0.056–0.369) | 0.439 (0.259–0.532) | Linear mixed effects |
| BgaA | Beta-galactosidase BgaA | SPD_0562 | 3.583 (2.453–4.350) | −0.034 (−0.060–0.030) | 0.031 (−0.030–0.130) | 0.235 (0.069–0.328) | 0.399 (0.194–0.601) | Both |
| CBD | Choline-binding domain | - | 0.937 (0.579–1.498) | −0.106 (−0.118 - −0.027) | 0.086 (0.031–0.135) | 0.204 (0.157–0.215) | 0.589 (0.357–0.658) | Both |
| CibA | Competence-induced bacteriocin A | SPD_0133 | 0.678 (0.566–1.072) | 0.007 (−0.049–0.061) | 0.756 (0.173–1.957) | 0.755 (0.363–1.435) | 1.261 (0.228–2.579) | Linear mixed effects |
| CLS00168 | Uncharacterised membrane protein | SPD_0093 | 2.540 (1.470–3.075) | −0.069 (−0.116–0.040) | 0.238 (0.136–0.631) | 0.031 (0.005–0.039) | 0.422 (0.233–0.601) | Linear mixed effects |
| CLS00229 | Uncharacterised membrane protein | SPD_0174 | 0.204 (0.132–0.397) | 0.004 (−0.124–0.043) | 0.127 (0.021–0.291) | 0.032 (0.000–0.146) | 0.602 (0.263–1.727) | Both |
| CLS00234 | Uncharacterised lipoprotein | SPD_0179 | 3.575 (2.996–4.215) | −0.028 (−0.060–0.016) | 0.035 (0.004–0.114) | −0.033 (−0.066–0.145) | 0.522 (0.284–0.829) | Both |
| CLS00386 | Uncharacterised membrane protein | SPD_0342 | 3.870 (3.551–4.418) | −0.011 (−0.050–0.049) | 0.207 (0.148–0.301) | 0.160 (0.054–0.322) | 0.370 (0.180–0.517) | Both |
| CLS01171 | Conjugative element protein | - | 1.156 (0.968–1.327) | −0.049 (−0.139 - −0.016) | 0.020 (−0.048–0.108) | 0.042 (−0.050–0.058) | 0.146 (0.072–0.290) | Empirical Bayes |
| CLS01337 | Uncharacterised membrane protein | SPD_1380 | 1.123 (0.603–1.572) | −0.061 (−0.168–0.053) | 0.187 (0.007–0.987) | 0.132 (0.038–0.183) | 0.912 (0.708–1.116) | Both |
| CLS01383 | Uncharacterised membrane protein | SPD_1429 | 4.805 (3.976–5.309) | −0.015 (−0.058–0.006) | 0.190 (0.123–0.281) | 0.088 (0.043–0.340) | 0.226 (0.194–0.504) | Linear mixed effects |
| CLS01446 | Sialic acid and N-acetylmannosamine ABC transporter permease | SPD_1500 | 0.033 (−0.086–0.080) | −0.118 (−0.175 - −0.074) | 0.074 (−0.039–0.175) | 0.073 (0.062–0.126) | 0.187 (−0.004–0.259) | Linear mixed effects |
| CLS01563 | ROK-family transcriptional repressor protein | - | 1.502 (1.030–1.894) | −0.098 (−0.141 - −0.039) | 0.049 (−0.045–0.499) | 0.028 (−0.003–0.044) | 0.248 (0.172–0.653) | Linear mixed effects |
| CLS01820 | Uncharacterised exported protein | SPD_1928 | 0.118 (−0.012–0.276) | −0.045 (−0.064–0.075) | 0.092 (0.012–0.152) | 0.118 (0.048–0.123) | 0.261 (0.102–0.460) | Both |
| CLS02831 | Bacteriocin ABC processing efflux pump | SPD_1752 | 1.000 (0.685–1.397) | −0.013 (−0.124–0.038) | 0.135 (0.058–0.236) | 0.110 (0.074–0.178) | 0.375 (0.299–0.485) | Both |
| CLS02897 | Uncharacterised membrane protein (fragment) | - | 0.683 (0.469–0.887) | −0.066 (−0.198–0.131) | 0.085 (−0.003–0.136) | 0.120 (0.061–0.248) | 0.175 (0.075–0.243) | Linear mixed effects |
| DnaK | Chaperone protein DnaK | SPD_0460 | 0.275 (0.178–0.657) | −0.041 (−0.219–0.013) | 0.059 (−0.015–0.100) | 0.088 (0.001–0.236) | 0.375 (0.020–2.027) | Linear mixed effects |
| Dpr | DNA protection during starvation stress resistance protein Dpr | SPD_1402 | 0.988 (0.467–1.541) | 0.038 (−0.056–0.223) | 0.114 (0.034–0.219) | 0.192 (−0.031–0.462) | 0.149 (0.066–0.366) | Linear mixed effects |
| EzrA | Septation ring formation regulator EzrA | SPD_0710 | 2.400 (1.520–3.755) | −0.016 (−0.041–0.002) | 0.195 (0.096–0.258) | 0.100 (−0.014–0.120) | 0.560 (0.140–0.646) | Both |
| FabE | Biotin carboxyl carrier protein of acetyl-CoA carboxylase FabE | SPD_0386 | −0.206 (−0.459–0.513) | −0.021 (−0.119–0.031) | 0.187 (0.033–0.274) | 0.270 (0.100–0.295) | 0.408 (0.014–0.716) | Linear mixed effects |
| FrlR | HTH-type transcriptional repressor FrlR | SPD_0064 | 0.445 (0.205–0.942) | −0.039 (−0.085–0.071) | 0.615 (0.117–1.452) | 0.283 (0.231–0.730) | 1.986 (1.454–2.437) | Both |
| FruA | Fructose PTS transporter protein FruA | SPD_0773 | 1.044 (0.568–1.389) | −0.029 (−0.125 - −0.002) | 0.480 (0.118–0.817) | 0.335 (0.322–0.360) | 0.591 (0.406–0.770) | Linear mixed effects |
| GalT | Galactose-1-phosphate uridylyltransferase GalT | SPD_1633 | 0.295 (0.211–0.494) | −0.024 (−0.055–0.047) | −0.110 (−0.220 - −0.034) | −0.068 (−0.082–0.012) | −0.018 (−0.129 - −0.005) | Linear mixed effects |
| GlnH | ABC glutamine transporter solute-binding protein GlnH | SPD_1226 | 2.912 (1.858–4.006) | 0.047 (−0.094–0.099) | 0.192 (0.059–0.274) | 0.289 (0.204–0.393) | 0.770 (0.336–1.163) | Both |
| GlnPH1 | Glutamine ABC transporter permease GlnPH1 | SPD_0412 | 1.029 (0.573–1.920) | −0.026 (−0.046–0.169) | 0.178 (0.133–0.387) | 0.278 (0.105–0.447) | 0.495 (0.258–0.576) | Both |
| GlnPH4 | Amino acid ABC transporter permease GlnPH4 | SPD_1098 | 4.006 (3.344–4.515) | 0.083 (−0.016–0.317) | 0.089 (0.019–0.155) | 0.154 (0.006–0.296) | 0.269 (0.173–0.367) | Linear mixed effects |
| GroEL | Chaperonin GroEL | SPD_1709 | 2.252 (1.129–3.083) | −0.057 (−0.101–0.010) | 0.396 (0.194–0.571) | 0.068 (−0.033–0.856) | 0.426 (0.107–0.963) | Both |
| HtrA | Surface-associated serine protease HtrA | SPD_2068 | 2.617 (2.002–3.293) | 0.011 (−0.000–0.061) | 0.262 (0.102–0.578) | 0.052 (0.029–0.297) | 0.519 (0.220–0.816) | Both |
| HylD | Efflux pump protein HylD | SPD_0686 | 4.590 (4.065–4.848) | −0.045 (−0.091–0.011) | 0.177 (−0.027–0.295) | 0.259 (0.083–0.264) | 0.319 (0.178–0.489) | Linear mixed effects |
| LemA | Uncharacterised membrane protein LemA | SPD_1139 | 0.473 (0.151–1.041) | −0.003 (−0.103–0.103) | 0.170 (0.110–0.457) | 0.300 (0.004–0.392) | 0.855 (0.635–2.035) | Both |
| LytA | Lytic amidase A | SPD_1737 | 3.547 (2.672–3.735) | 0.032 (−0.094–0.103) | 0.098 (0.029–0.221) | 0.021 (−0.012–0.066) | 0.158 (0.067–0.190) | Linear mixed effects |
| LytR | Teichoic acid attachment protein LytR | SPD_1741 | 4.015 (3.488–4.455) | 0.022 (−0.087–0.084) | 0.149 (−0.003–0.235) | 0.074 (−0.052–0.080) | 0.217 (0.152–0.299) | Linear mixed effects |
| ManL | Glucose, mannose, galactose, fructose, N-acetylglucosamine and glucosamine ABC transporter ATPase ManL | SPD_0264 | 0.803 (0.374–1.553) | 0.000 (−0.104–0.059) | 0.460 (0.129–0.907) | 0.070 (0.052–0.469) | 1.083 (0.833–1.346) | Both |
| MltG | Endolytic murein transglycosylase MltG | SPD_1346 | 2.993 (2.330–3.371) | −0.087 (−0.119–0.055) | 0.249 (0.110–0.283) | 0.253 (0.060–0.401) | 0.491 (0.338–0.753) | Both |
| MreC | Peptidoglycan formation protein C MreC | SPD_2045 | 2.947 (1.440–4.467) | 0.133 (−0.048–0.199) | 0.092 (−0.021–0.219) | 0.123 (0.095–0.138) | 0.172 (0.076–0.344) | Linear mixed effects |
| Pbp1a | Penicillin-binding protein 1A | SPD_0336 | 1.543 (0.999–1.915) | −0.066 (−0.111–0.049) | 0.138 (0.016–0.256) | 0.082 (0.042–0.092) | 0.357 (0.192–0.734) | Both |
| Pbp1b | Penicillin-binding protein 1B | SPD_1925 | 0.615 (0.366–0.867) | −0.039 (−0.088–0.001) | 0.023 (−0.004–0.151) | 0.070 (−0.056–0.157) | 0.216 (0.108–0.412) | Empirical Bayes |
| Pbp2b | Penicillin-binding protein 2B | SPD_1486 | 4.348 (3.623–4.958) | −0.017 (−0.105–0.065) | 0.161 (0.037–0.293) | 0.426 (0.137–0.532) | 0.520 (0.189–0.770) | Both |
| Pbp2x | Penicillin-binding protein 2X | SPD_0306 | 2.934 (2.261–3.653) | 0.044 (−0.082–0.262) | 0.245 (0.012–0.426) | 0.174 (0.041–0.616) | 0.626 (0.315–1.174) | Both |
| Pbp3 | D-alanyl-D-alanine carboxypeptidase Pbp3 | SPD_0767 | 1.981 (1.253–3.408) | 0.006 (−0.031–0.036) | 0.053 (−0.030–0.137) | 0.042 (−0.020–0.448) | 0.209 (0.121–0.741) | Linear mixed effects |
| PclA | Pneumococcal collagen-like protein A | SPD_1376 | 0.638 (0.317–0.984) | −0.066 (−0.154 - −0.002) | 0.078 (−0.047–0.248) | 0.063 (0.007–0.163) | 0.177 (0.067–0.321) | Both |
| PgdA | Peptidoglycan-N-acetylglucosamine deacetylase PgdA | SPD_1309 | 2.407 (1.971–3.550) | −0.089 (−0.135–0.041) | 0.438 (0.154–0.812) | 0.111 (−0.004–0.286) | 0.511 (0.197–0.986) | Both |
| PiaA | Iron ABC transporter substrate-binding protein PiaA | SPD_0915 | 4.442 (4.142–4.795) | 0.001 (−0.076–0.086) | 0.086 (0.047–0.148) | 0.143 (0.127–0.145) | 0.287 (0.191–0.357) | Linear mixed effects |
| PiuA | Iron ABC transporter solute-binding protein PiuA | SPD_1652 | 3.593 (2.744–4.086) | 0.011 (−0.078–0.034) | 0.088 (−0.020–0.203) | 0.106 (0.091–0.167) | 0.410 (0.276–0.452) | Both |
| Ply | Pneumolysin | SPD_1726 | 1.306 (0.576–1.604) | −0.120 (−0.158 - −0.068) | 0.393 (0.205–0.428) | 0.338 (0.313–0.478) | 0.322 (0.162–0.799) | Both |
| PnrA | Ribonucleoside ABC transporter solute- binding protein | SPD_0739 | 4.634 (4.086–4.998) | −0.028 (−0.072–0.043) | 0.116 (0.047–0.203) | 0.084 (0.073–0.262) | 0.205 (0.112–0.464) | Linear mixed effects |
| PpmA | Foldase protein PpmA | SPD_0868 | 3.531 (2.883–4.059) | 0.079 (−0.078–0.112) | 0.412 (0.226–0.578) | 0.284 (0.264–0.825) | 0.594 (0.263–0.727) | Linear mixed effects |
| PppL | Protein phosphatase PhpP | SPD_1543 | 0.906 (0.711–1.867) | −0.066 (−0.253–0.005) | −0.066 (−0.195–0.189) | 0.021 (0.008–0.089) | 0.443 (0.055–0.630) | Empirical Bayes |
| PspA | Pneumococcal surface protein A | SPD_0126 | 3.616 (2.076–4.672) | −0.032 (−0.124–0.051) | 0.124 (0.023–0.241) | 0.144 (0.022–0.280) | 0.301 (0.103–0.484) | Both |
| PspC | Pneumococcal surface protein C | SPD_2017 | 2.810 (1.334–3.682) | −0.066 (−0.122–0.034) | 0.122 (−0.001–0.212) | 0.124 (0.060–0.188) | 0.285 (0.156–0.452) | Both |
| Psr | Teichoic acid attachment protein Psr | SPD_1202 | 2.198 (1.514–2.946) | −0.028 (−0.081–0.069) | 0.161 (0.023–0.212) | 0.120 (0.089–0.333) | 0.328 (0.222–0.548) | Linear mixed effects |
| PstS2 | Phosphate ABC transporter solute-binding protein PstS2 | SPD_1232 | 3.479 (1.676–4.508) | 0.021 (−0.010–0.134) | 0.203 (−0.091–0.613) | −0.034 (−0.037 - −0.012) | 0.603 (0.314–0.945) | Linear mixed effects |
| PyrK | Dihydroorotate dehydrogenase B (NAD(+)) electron transfer subunit PyrK | SPD_0851 | 0.809 (0.643–0.991) | −0.087 (−0.139 - −0.020) | 0.032 (−0.080–0.058) | 0.014 (0.002–0.018) | 0.182 (0.143–0.225) | Empirical Bayes |
| QmcA | Membrane-associated protease regulator QmcA | SPD_1984 | 1.297 (0.852–1.812) | −0.041 (−0.094–0.013) | 1.144 (0.435–1.718) | 0.776 (0.643–1.311) | 1.249 (0.857–2.103) | Both |
| RexA | ATP-dependent helicase/nuclease subunit RexA | SPD_1016 | 0.443 (0.110–1.147) | −0.047 (−0.159–0.058) | 0.052 (−0.010–0.167) | 0.068 (0.024–0.073) | 0.401 (0.183–0.547) | Empirical Bayes |
| RmuC | DNA recombination protein RmuC | SPD_1778 | 2.496 (2.268–3.737) | −0.042 (−0.091–0.065) | 0.197 (0.080–0.241) | −0.006 (−0.041–0.092) | 0.253 (0.129–0.385) | Both |
| SepF | Cell division protein SepF | SPD_1477 | 0.427 (−0.263–1.073) | 0.079 (0.018–0.177) | 0.182 (0.033–0.646) | 0.083 (0.056–0.332) | 0.766 (0.324–1.050) | Both |
| SlrA or PpiA | Peptidyl-prolyl cis-trans isomerase SlrA or PpiA | SPD_0672 | 1.920 (1.103–3.274) | −0.006 (−0.061–0.091) | 0.551 (0.297–0.988) | 0.732 (0.691–0.858) | 1.360 (1.190–2.095) | Both |
| StkP | Serine/threonine-protein kinase StkP | SPD_1542 | 3.847 (3.282–4.111) | 0.047 (0.013–0.110) | 0.112 (0.096–0.124) | −0.004 (−0.076–0.087) | 0.178 (0.107–0.252) | Linear mixed effects |
| TagB | Membrane-associated protein TagB | SPD_1197 | 0.956 (0.797–1.621) | −0.038 (−0.075–0.075) | 0.074 (0.029–0.130) | 0.162 (0.145–0.163) | 0.124 (0.083–0.212) | Linear mixed effects |
| TcyA | ABC amino acid transporter solute-binding protein TcyA | SPD_0150 | 1.815 (1.279–2.538) | −0.096 (−0.160–0.055) | 1.117 (0.849–1.319) | 1.025 (0.324–1.724) | 0.947 (0.477–2.225) | Both |
| TprA | Quorum-sensing PclR-type transcriptional regulator TprA | SPD_1745 | 1.008 (0.654–1.284) | −0.054 (−0.099 - −0.039) | 0.029 (−0.092–0.095) | 0.056 (0.010–0.205) | 0.394 (0.237–0.474) | Both |
| Tuf | Elongation factor Tu | SPD_1318 | 0.306 (−0.003–1.146) | −0.065 (−0.323–0.006) | 0.777 (0.246–1.589) | −0.003 (−0.189–0.001) | 1.107 (0.481–1.483) | Both |
| YajC | Preprotein translocase YajC subunit | SPD_1838 | 1.580 (1.060–2.363) | −0.051 (−0.133–0.021) | 0.967 (0.494–2.145) | 1.454 (0.740–1.689) | 1.610 (0.977–2.225) | Both |
| YbbR | Uncharacterised protein YbbR | SPD_1391 | 3.584 (2.730–4.405) | −0.015 (−0.094–0.146) | 0.021 (−0.057–0.131) | −0.021 (−0.034–0.110) | 0.199 (0.060–0.540) | Linear mixed effects |
| YneF | Uncharacterised protein YneF | SPD_1662 | 0.187 (0.042–0.419) | −0.060 (−0.090–0.015) | 0.047 (−0.083–0.266) | 0.263 (0.133–0.299) | 0.314 (0.209–0.544) | Linear mixed effects |
| YoxC | Uncharacterised membrane protein YoxC | SPD_1242 | 0.160 (0.083–0.368) | 0.093 (0.041–0.170) | 0.107 (0.018–0.251) | 0.183 (0.123–0.226) | 0.410 (0.123–1.580) | Linear mixed effects |
| ZmpA | Zinc metalloprotease A | SPD_1018 | 3.084 (1.841–4.307) | −0.031 (−0.110–0.085) | 0.161 (0.043–0.288) | 0.142 (0.016–0.279) | 0.479 (0.260–0.700) | Both |
| ZmpB | Zinc metalloprotease B | SPD_0577 | 1.149 (0.436–2.096) | −0.042 (−0.152–0.032) | 0.127 (−0.031–0.206) | 0.089 (−0.037–0.202) | 0.139 (0.069–0.264) | Both |