Biological sex influences antibody responses to routine vaccinations in the first year of life

Biological sex influences antibody responses to routine

vaccinations in the first year of life

Petra Zimmermann

1,2,3,4

Պ| Kirsten P. Perrett

5,6,7

Պ| Nicole Ritz

1,8

Պ| Katie L. Flanagan

9

Պ|

Roy Robins-Browne

2,10

Պ| Fiona R. M. van der Klis

11

Պ| Nigel Curtis

1,2,3

Պ| the MIS BAIR group

*

1 ;r-u|l;m|o=-;7b-|ub1vķ$_;&mbˆ;uvb|‹o=;Ѵ0o†um;ķ-uhˆbѴѴ;ķ(b1|oub-ķ†v|u-Ѵb-2 m=;1|bo†v bv;-v;v!;v;-u1_uo†rķ†u7o1__bѴ7u;mŝv!;v;-u1_mv|b|†|;ķ-uhˆbѴѴ;ķ(b1|oub-ķ†v|u-Ѵb-3 m=;1|bo†v bv;-v;v&mb|ķ$_;!o‹-Ѵ_bѴ7u;mŝvovrb|-Ѵ;Ѵ0o†um;ķ-uhˆbѴѴ;ķ(b1|oub-ķ†v|u-Ѵb-4 _{;r-u|l;m|o=-;7b-|ub1vķ ub0o†u]ovrb|-Ѵ !-m7 -1†Ѵ|‹o="1b;m1;-m7;7b1bm;ķ&mbˆ;uvb|‹o= ub0o†u]ķ ub0o†u]ķ"‰b|Œ;uѴ-m7} Ɣ oo7ѴѴ;u]‹!;v;-u1_uo†r-m7;Ѵ0o†um;_bѴ7u;mŝv$ub-Ѵ;m|u;ķ†u7o1__bѴ7u;mŝv!;v;-u1_mv|b|†|;ķ-uhˆbѴѴ;ķ(b1|oub-ķ†v|u-Ѵb-6 ;r-u|l;m|vo=ѴѴ;u]‹-m7ll†moѴo]‹-m7;m;u-Ѵ;7b1bm;ķ!o‹-Ѵ_bѴ7u;mŝvovrb|-Ѵķ;Ѵ0o†um;ķ-uhˆbѴѴ;ķ(b1|oub-ķ†v|u-Ѵb-7 "1_ooѴo=or†Ѵ-|bom-m7Ѵo0-Ѵ;-Ѵ|_ķ$_;&mbˆ;uvb|‹o=;Ѵ0o†um;ķ-uhˆbѴѴ;ķ(b1|oub-ķ†v|u-Ѵb-8_{m=;1|bo†v bv;-v;v&mb|ķ&mbˆ;uvb|‹o=-v;Ѵ_bѴ7u;mŝvovrb|-Ѵķ-v;Ѵķ"‰b|Œ;uѴ-m7} 9 &mbˆ;uvb|‹o=$-vl-mb-ķ-†m1;v|om-m7om-v_&mbˆ;uvb|‹ķѴ-‹|omķ(b1|oub-ķ†v|u-Ѵb-10 ;r-u|l;m|o=b1uo0boѴo]‹-m7ll†moѴo]‹ķ$_;&mbˆ;uvb|‹o=;Ѵ0o†um;ķ-uhˆbѴѴ;ķ(b1|oub-ķ†v|u-Ѵb-11_{;m|u;=oum=;1|bo†v bv;-v;vķ-|bom-Ѵmv|b|†|;o=†0Ѵb1;-Ѵ|_-m7|_;mˆbuoml;m|ķbѴ|_oˆ;mķ$_;;|_;uѴ-m7v} *"!]uo†rĹ(;uomb1-0u†ŒŒoķ-|b;ѴѴ;mķ!_b-mommb1bķ -m-v-Ѵ-Œķ-mm-_Ѵ0ouo†]_ķub7];| u;‹m;ķ-‹--u7bm;uķ"†vb;;ul-moķ$o0b-voѴѴl-mmķb1oѴ;;vvbm-ķѴ-u; ouubvomķ;Ѵ7;u-h-‹-ķmm;o†bv;omvom0‹ķ u-mh"_-mmķbh;"o†|_ķ;|;u(†bѴѴ;ulbm Abbreviations:ķ-1bѴѴ;-Ѵl;||;Ŋ†࣐ubmĸķ1om=b7;m1;bm|;uˆ-Ѵĸ $-ķ7br_|_;ub-Ŋ|;|-m†vŊ-1;ѴѴ†Ѵ-ur;u|†vvbvˆ-11bm;ĸ ķ=bѴ-l;m|o†v_-;l-]]Ѵ†|bmbmĸķ];ol;|ub1l;-m 1om1;m|u-|bomĸ!ķ];ol;|ub1l;-mu-|boĸ;rķ_;r-|b|bvĸ;rķ_;r-|b|bvĸb0ķHaemophilus influenzae|‹r;0ĸ]ķbll†mo]Ѵo0†Ѵbmĸ(ķbm-1|bˆ-|;7roѴboˆ-11bm;ĸ !ķ bm|;ut†-u|bѴ;u-m];ĸ;mķl;mbm]o1o11†vĸ"!ķ$_;;Ѵ0o†um;m=-m|"|†7‹Ĺ=ouѴѴ;u]‹-m7m=;1|bom!;7†1|bomĸ!(ķou-Ѵuo|-ˆbu†vˆ-11bm;ĸ(ƐƒķƐƒŊˆ-Ѵ;m|1omf†]-|; rm;†lo1o11-Ѵˆ-11bm;ĸmķrm;†lo1o11-Ѵv;uo|‹r;ĸ!ķr;u|-1|bmĸ$ķr;u|†vvbv|oŠbmĺ Correspondence b];Ѵ†u|bvķ ;r-u|l;m|o=-;7b-|ub1vķ$_; &mbˆ;uvb|‹o=;Ѵ0o†um;ķ!o‹-Ѵ_bѴ7u;mŝv ovrb|-Ѵ;Ѵ0o†um;ķ-uhˆbѴѴ;ķ(ƒƏƔƑķ †v|u-Ѵb-ĺ l-bѴĹmb];Ѵĺ1†u|bvŠu1_ĺou]ĺ-† Funding information $_bv‰ouh‰-vv†rrou|;70‹|_;†v|u-Ѵb-m -|bom-Ѵ;-Ѵ|_-m7;7b1-Ѵ!;v;-u1_ o†m1bѴŐ!őŐ]u-m|v$ƐƏƔƐƑƑѶ-m7 $ƐƏƖƖѵѶƏőķ|_;&mbˆ;uvb|‹o=;Ѵ0o†um; Őm|;um-|bom-Ѵ!;v;-u1_"1_oѴ-uv_br|o,ő -m7|_;†uor;-m"o1b;|‹o=-;7b-|ub1 m=;1|bo†v bv;-v;vŐ" őŐ=;ѴѴo‰v_br|o ,őĺ

Abstract

Aim: ); bmˆ;v|b]-|;7 |_; ;==;1| o= ;-uѴ‹ŊѴb=; =-1|ouvķ m-l;Ѵ‹ v;Šķ 7;Ѵbˆ;u‹ lo7;ķ

=;;7bm]l;|_o7-m7-m|b0bo|b1;Šrov†u;ķom-m|b0o7‹u;vromv;v|ouo†|bm;ˆ-11bm-Ŋ |bomv-7lbmbv|;u;77†ubm]|_;=buv|‹;-uo=Ѵb=;ĺ Methods: m;-m7v;ˆ;mlom|_v-=|;u|_;rubl-u‹1o†uv;o=uo†|bm;ˆ-11bm;v-m7 Ɛlom|_-=|;uuo†|bm;ˆ-11bm;v-|ƐƑlom|_vo=-];ķ-m|b0o7b;v-]-bmv|Ƒѵˆ-11bm; -m|b];mv‰;u;l;-v†u;7bmƒƖѶ_;-Ѵ|_‹bm=-m|vĺ$_;];ol;|ub1l;-m1om1;m|u-|bom Őőo=-m|b0o7b;vŐ-7f†v|;7=ou;==;1|lo7b=b;uv‰b|_l†Ѵ|brѴ;Ѵbm;-uu;]u;vvbomő-m7 |_;v;uoruo|;1|bomu-|;=ou;-1_ˆ-11bm;‰;u;1olr-u;7=ou;-1_;-uѴ‹ŊѴb=;=-1|ouĺ Results: ";Š_-7-mbm=Ѵ†;m1;omvĺm|b0o7‹1om1;m|u-|bomv‰;u;vb]mb=b1-m|Ѵ‹Ѵo‰;u -|ƕlom|_vo=-];bm=;l-Ѵ;v=ou|;|-m†v-m7=bѴ-l;m|o†v_-;l-]]Ѵ†|bmbm-m7-|Ɛƒlom|_v o=-];=our;u|-1|bmĺm1om|u-v|ķ-|Ɛƒlom|_vo=-];ķ-m|b0o7‹1om1;m|u-|bomv‰;u;vb]mb=bŊ 1-m|Ѵ‹_b]_;ubm=;l-Ѵ;v=ouroѴbo|‹r;ƒķrm;†lo1o11-Ѵv;uo|‹r;ѵ-m7l;-vѴ;vĺ";Š7b7 mo|_-ˆ;-mbm=Ѵ†;m1;omv;uoruo|;1|bomu-|;vĺ ;Ѵbˆ;u‹lo7;ķ=;;7bm]l;|_o7-m7-m|bŊ 0bo|b1;Šrov†u;7b7mo|;Š;u|-v†0v|-m|b-Ѵbm=Ѵ†;m1;omˆ-11bm;-m|b0o7‹1om1;m|u-|bomvĺ

Conclusion: $_;u; bv - 7b==;u;m1; 0;|‰;;m l-Ѵ;v -m7 =;l-Ѵ;v bm |_; _†lou-Ѵ u;Ŋ

vromv;|ouo†|bm;ˆ-11bm-|bomvbm|_;=buv|‹;-uo=Ѵb=;ĺ

K E Y W O R D S

-m|b0o7b;vķ_†lou-Ѵķbll†mbv-|bomķbll†mo]Ѵo0†Ѵbmķbm=-m|ķ|b|u;

http://doc.rero.ch

Published in "Acta Paediatrica doi: 10.1111/apa.14932, 2019"

which should be cited to refer to this work.

ƐՊ|Պ $! &  $  

(-11bm-|bombvom;o=|_;lov|1ov|Ŋ;==;1|bˆ;ķѴb=;Ŋv-ˆbm]l;7b1-ѴbmŊ |;uˆ;m|bomvĺo‰;ˆ;uķ|_;u;bvv†0v|-m|b-Ѵˆ-ub-|bom0;|‰;;mbm7bˆb7Ŋ †-Ѵvbm|_;l-]mb|†7;o=|_;bll†m;u;vromv;|oˆ-11bm-|bomķ‰_b1_ lb]_|_-ˆ;blrѴb1-|bomv=ou0o|_ruo|;1|bˆ;;==b1-1‹-m77†u-|bomo= ruo|;1|bomĺ||_;-];o=ѵlom|_vķ=ou;Š-lrѴ;ķ-m|b0o7‹u;vromv;v |orm;†lo1o11-Ѵ-m7Haemophilus influenzae|‹r;0Őb0őˆ-11bm;v l-‹ˆ-u‹†r|oƓƏŊ=oѴ7ĺ1

 m†l0;u o= bm|ubmvb1 _ov|ķ r;ubm-|-Ѵ -m7 ;Š|ubmvb1 =-1|ouv -u; Ѵbh;Ѵ‹|o1om|ub0†|;|o|_;ˆ-ub-|bombmˆ-11bm;u;vromv;vĺ2m;o= |_; bm|ubmvb1 =-1|ouv |_-| _-v 0;;m lov| bmˆ;v|b]-|;7 bv 0boѴo]b1-Ѵ v;Šĺ †| v|†7b;v |o 7-|; _-ˆ; -Ѵlov| ;Š1Ѵ†vbˆ;Ѵ‹ 0;;m bm -7†Ѵ|vĺ |_;u bm|ubmvb1 =-1|ouv bm1Ѵ†7; roѴ‹lour_bvlv bm ];m;v ;m1o7bm] l-fou _bv|o1olr-|b0bѴb|‹ 1olrѴ;Š;v ou r-||;um u;1o]mb|bom u;1;rŊ |ouvķv†1_-v$oѴѴŊѴbh;ou!ŊѴbh;u;1;r|ouvĺ2;ubm-|-Ѵ=-1|ouv|_-| lb]_| bm=Ѵ†;m1; ˆ-11bm; u;vromv;v bm1Ѵ†7; ];v|-|bom-Ѵ -];ķ 0bu|_Ŋ ‰;b]_|ƒķƓ-m7=;;7bm]l;|_o7Ő=oul†Ѵ-ˆv0u;-v|=;7őĺo|;m|b-Ѵ;ŠŊ |ubmvb1=-1|ouvbm1Ѵ†7;;Šrov†u;|oruo0bo|b1v-m7-m|b0bo|b1vĺ)_bѴ; |_;u; bv ;ˆb7;m1; =ou - 0;m;=b1b-Ѵ ;==;1| o= ruo0bo|b1v om ˆ-11bm; u;vromv;vķ2|o7-|;ķomѴ‹om;v|†7‹_-vbmˆ;v|b]-|;7|_;;==;1|o= -m|b0bo|b1v om ˆ-11bm; u;vromv;v bm _†l-mvĺ $_bv v|†7‹ u;rou|;7 |_-| -7lbmbv|u-|bom o= -m|b0bo|b1v 0;=ou; ˆ-11bm-|bom 7b7 mo| -Ѵ|;u v;u†lbll†mo]Ѵo0†ѴbmŐ]ő1om1;m|u-|bomv|oou-Ѵuo|-ˆbu†vˆ-1Ŋ 1bm;Ő!(őbm-7†Ѵ|vĺƔ

;|;ulbmbm] |_; bm=Ѵ†;m1; o= bm|ubmvb1 -m7 ;Š|ubmvb1 =-1|ouv om ˆ-11bm;-m|b0o7‹u;vromv;v_-vblrѴb1-|bomv=ouor|blbvbm]ˆ-11bm; u;1oll;m7-|bomv-m7bm7bˆb7†-Ѵbvbm]ˆ-11bm;v1_;7†Ѵ;vĺ m|_bvv|†7‹ķ‰;bmˆ;v|b]-|;7|_;;==;1|o=0boѴo]b1-Ѵv;Šķlo7; o=7;Ѵbˆ;u‹ķ=;;7bm]l;|_o7-m7-m|b0bo|b1;Šrov†u;om-m|b0o7‹u;Ŋ vromv;v|ouo†|bm;ˆ-11bm-|bomv]bˆ;mbm|_;=buv|‹;-uo=Ѵb=;ĺ

ƑՊ|Պ  $  "

ƑĺƐՊ|Պ"|†7‹7;vb]m-m7ror†Ѵ-|bom

-u|b1br-m|v ‰;u; - v†0v;| o= ƓƕƐ _;-Ѵ|_‹ bm=-m|v =uol $_; ;Ѵ0o†um;m=-m|"|†7‹Ĺ-1bѴѴ;-Ѵl;||;Ŋ†࣐ubmŐő=ouѴѴ;u]‹ -m7m=;1|bom!;7†1|bomŐ"!őŐ_||rĹņņlbv0-buĺou]őĺm|_bv|ub-Ѵķ bm=-m|v‰;u;u;1u†b|;7-|0bu|_=uolƑƏƐƒ|oƑƏƐѵ-m7u-m7olbv;7|o u;1;bˆ;m;om-|-Ѵˆ-11bm-|bomoumobm|;uˆ;m|bom|obmˆ;v|b]-|; ‰_;|_;uruo|;1|v=uol1_bѴ7_oo7-ѴѴ;u]b;vĺm1Ѵ†vbom1ub|;ub-bmŊ 1Ѵ†7;7|_;=oѴѴo‰bm]ĹƻƒƑ‰;;hvŝ];v|-|bom-m70bu|_‰;b]_|ƻƐƔƏƏ]ĺ ;|-bѴv -0o†| =;;7bm] -m7 -m|b0bo|b1 ;Šrov†u; ‰;u; ruovr;1|bˆ;Ѵ‹ 1oѴѴ;1|;70‹r-u;m|t†;v|bomm-bu;ĺ

uol|_;v†0v;|o=r-u|b1br-m|v‰_ov;r-u;m|ņ]†-u7b-mruoŊ ˆb7;7 1omv;m|ķ 0Ѵoo7 v-lrѴ;v ‰;u; 1oѴѴ;1|;7 -| v|†7‹ ˆbvb|v -| ƕ -m7ņou Ɛƒ lom|_v o= -]; Ő7;vb]m;7 |o 0; Ɠ ‰;;hv -=|;u |_; -7lbmbv|u-|bom o= uo†|bm; v1_;7†Ѵ;7 ˆ-11bm-|bomvőĺ mѴ‹ r-u|b1bŊ r-m|v ‰_o _-7 - 0Ѵoo7 |-h;m ƑѶ Ƽ ƐƓ 7-‹v -=|;u |_;bu ѵŊlom|_ -m7ņou ƐƑŊlom|_ uo†|bm; ˆ-11bm-|bomv ‰;u; bm1Ѵ†7;7 bm |_; -m-Ѵ‹vbv o= bll;7b-|; rov|Ŋˆ-11bm-|bom u;vromv;vĺ ou |_ov; bm ‰_ol r;uvbv|;m1; o= -m|b0o7b;v |o |_;bu ѵŊlom|_ ˆ-11bm;v ‰-v

l;-v†u;7ķ 0Ѵoo7 ‰-v |-h;m ƕ lom|_v Ƽ Ƒƒ 7-‹v -=|;u |_;bu ѵŊ lom|_ˆ-11bm-|bomvĺ

ƑĺƑՊ|Պm=-m|ˆ-11bm-|bom

ѴѴbm=-m|vu;1;bˆ;7uo†|bm;ˆ-11bm-|bomv-11ou7bm]|o|_;†v|u-Ѵb-m -|bom-Ѵ ll†mbv-|bom uo]u-lĹ -| 0bu|_Ĺ bm|u-l†v1†Ѵ-u _;r-|bŊ |bv  Ő;rő ˆ-11bm; ŐŊŊ(-Š  -;7b-|ub1®ĸ 0bo"őĸ -| ѵ ‰;;hvķ Ɠlom|_v-m7ѵlom|_vo=-];Ĺbm|u-l†v1†Ѵ-u1ol0bm;77br_|_;ub-Ŋ |;|-m†vŊ-1;ѴѴ†Ѵ-ur;u|†vvbvŐ $-őŊ;rŊbm-1|bˆ-|;7roѴboŐ(őŊb0 ˆ-11bm;Őm=-mubŠ®;Š-ĸѴ-Šo"lb|_Ѵbm;őķbm|u-l†v1†Ѵ-u1omf†]-|; rm;†lo1o11-Ѵ ˆ-11bm; Ő(Ɛƒő Őu;ˆ;m-uƐƒ®ĸ )‹;|_ő -m7 !( Ő!o|-$;t®ĸ ;u1hőĸ -m7 -| ƐƑ lom|_v o= -];Ĺ v†01†|-m;o†v l;-Ŋ vѴ;vŊl†lrvŊu†0;ѴѴ-Ő!őˆ-11bm;ŐuboubŠ®ĸѴ-Šo"lb|_Ѵbm;ő-m7 bm|u-l†v1†Ѵ-u1ol0bm;7b0-m71omf†]-|;7l;mbm]o1o11-Ѵˆ-1Ŋ 1bm; Ő;mb|oubŠ®ĸ Ѵ-Šo"lb|_Ѵbm;őĺ rruoŠbl-|;Ѵ‹ _-Ѵ= o= |_; bmŊ =-m|v u;1;bˆ;7 bm|u-7;ul-Ѵ Ŋ ;ml-uh Ő"|-|;mv ";u†l mv|b|†|ķ or;m_-];mő v_ou|Ѵ‹ -=|;u 0bu|_ -v r-u| o= |_; " !ĺ (-11bm; u;1ou7v ‰;u; o0|-bm;7 =uol bm7bˆb7†-Ѵ ˆ-11bm-|bom u;1ou7v -m7ņou |_;†v|u-Ѵb-mll†mbv-|bom!;]bv|;uĺ

ƑĺƒՊ|ՊѴoo71oѴѴ;1|bom-m7-m|b0o7‹-vv-‹

oѴѴo‰bm] 1oѴѴ;1|bom Ő"Ŋlomoˆ;||;®ĸ "-uv|;7|őķ rѴ-vl- ‰-v v|ou;7 -| ƴѶƏŦ †m|bѴ -m-Ѵ‹vbv -| |_; -|bom-Ѵ mv|b|†|; =ou ;-Ѵ|_ -m7 mˆbuoml;m|ķbmbѴ|_oˆ;mķ|_;;|_;uѴ-m7vĺ]-m|b0o7b;v-]-bmv| Ƒѵ ˆ-11bm; -m|b];mv Ő7br_|_;ub-ķ |;|-m†vķ r;u|†vvbv Œr;u|†vvbv |oŠbm Œ$œķ =bѴ-l;m|o†v _-;l-]]Ѵ†|bmbm Œ œķ r;u|-1|bm Œ!œœőķ roѴbo Ő|‹r;vƐķƑķƒőķb0ķrm;†lo1o11†vŐv;uo|‹r;vƐķƒķƓķƔķѵķѵķƕ ķ Ɩ(ķƐƓķƐѶķƐƖķƐƖ ķƑƒ őķl;mbm]o1o11†v|‹r;Ő;mőķl;-vѴ;vķ l†lrv -m7 u†0;ѴѴ- ‰;u; l;-v†u;7 †vbm] =Ѵ†ou;v1;m| 0;-7Ŋ0-v;7 l†Ѵ|brѴ;Š bll†m; -vv-‹v Ő†lbm;Š Š |;1_moѴo]‹őĺ m -ѴѴ -vŊ v-‹vķ bm|;um-|bom-Ѵ ou bmŊ_o†v; u;=;u;m1; 1om|uoѴv -m7 0Ѵ-mhv ‰;u; bm1Ѵ†7;7 om ;-1_ rѴ-|;ĺ ѴѴ -m-Ѵ‹v;v ‰;u; r;u=oul;7 ‰b|_ - boŊ Ѵ;ŠƑƏƏbm1ol0bm-|bom‰b|_boŊѴ;Šl-m-];uvo=|‰-u;ŐboŊ!-7 -0ou-|oub;vőĺ

ƑĺƓՊ|Պ-|;]oubv-|bomo=r-u|b1br-m|v

m=-m|v‰;u;1-|;]oubv;70‹0boѴo]b1-Ѵv;ŠŐl-Ѵ;ou=;l-Ѵ;őķ7;Ѵbˆ;u‹ lo7;Ո-]bm-Ѵˆv1-;v-u;-mv;1|bomőķ=;;7bm]l;|_o7-m7-m|b0bo|b1 Key notes Ŏ $_;u;-u;v†0v|-m|b-Ѵ7b==;u;m1;v0;|‰;;mbm7bˆb7†-Ѵvbm |_;bll†m;u;vromv;|oˆ-11bm-|bomĺ

Ŏ m |_bv v|†7‹ķ ‰; =o†m7 |_-| |_;u; -u; 7b==;u;m1;v 0;Ŋ |‰;;ml-Ѵ;v-m7=;l-Ѵ;vbm-m|b0o7‹u;vromv;v|ouo†Ŋ |bm;ˆ-11bm-|bomvbm|_;=buv|‹;-uo=Ѵb=;ĺ

Ŏ m1om|u-v|ķ7;Ѵbˆ;u‹lo7;ķ=;;7bm]l;|_o7-m7-m|b0bŊ o|b1;Šrov†u;7b7mo|-==;1|-m|b0o7‹u;vromv;vĺ

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ƑĺƔՊ|Պ"|-|bv|b1-Ѵ-m-Ѵ‹vbv

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ƑĺѵՊ|Պ|_b1v

m=oul;71omv;m|‰-vo0|-bm;7=uolr-u|b1br-m|vŝr-u;m|vou]†-u7Ŋ b-mvĺ $_; v|†7‹ ‰-v -rruoˆ;7 0‹ |_; !o‹-Ѵ _bѴ7u;mŝv ovrb|-Ѵ †l-m!;v;-u1_|_b1vollb||;;Ő!ķ-†|_oubv-|bomķƒѶƐƑƓőĺ

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=|_;ƒѵƔbm=-m|vķƐƕƖŐƓƖѷő‰;u;l-Ѵ;ķƐƒƕŐƒƕѷő‰;u;0oum0‹ 1-;v-u;-mv;1|bomķ-m7ƐƏƏŐƑѶѷő_-7u;1;bˆ;7=oul†Ѵ-lbѴh0;=ou; 7bv1_-u]; =uol |_;bu 0bu|_ _ovrb|-Ѵĺ | Ɛ lom|_ o= -];ķ ƒƏƑ ŐѶƒѷő bm=-m|v‰;u;v|bѴѴu;1;bˆbm]0u;-v|lbѴhķ-m7-|ѵlom|_vo=-];ķ|_bv m†l0;u‰-vƑѵƒŐƕƑѷőĺm|o|-ѴķƕƏŐƐƖѷőlo|_;uvu;1;bˆ;7-m|b0bŊ o|b1v 7†ubm] 7;Ѵbˆ;u‹Ĺ ƒѵ ŐƔƐѷő 0;1-†v; |_;‹ ‰;u; 1oѴombv;7 ‰b|_ ]uo†r  v|u;r|o1o11†vķ Ƒƕ ŐƒƖѷő 0;1-†v; o= ruoѴom];7 u†r|†u; o= l;l0u-m;vķ Ɣ Őƕѷő 0;1-†v; o= 1-;v-u;-m v;1|bom 7;Ѵbˆ;u‹ -m7 =ou Ƒ Őƒѷő |_; u;-vom ‰-v mo| vr;1b=b;7ĺ $_; -7lbmbv|;u;7 -m|b0bo|b1v ‰;u;0;mŒ‹Ѵr;mb1bѴѴbmŐmƷƒƏőķ-loŠ‹1bѴѴbmŐmƷƐƓőķ-lrb1bѴѴbmŐmƷƐƐőķ 1;=-ŒoѴbmŐmƷƔőķ1;=o|-Šbl;ŐmƷƐőķl;|uomb7-ŒoѴ;ŐmƷƐő-m7mo| vr;1b=b;7ŐmƷƐƐőĺ

m|b0bo|b1v‰;u;-7lbmbv|;u;7|oƒƏŐѶѷőbm=-m|v0;=ou;|_;bu =buv| uo†|bm; ˆ-11bm-|bom v1_;7†Ѵ; -| ѵ ‰;;hv o= Ѵb=;ĺ $_;v; bmŊ =-m|vu;1;bˆ;7omѴ‹om;1o†uv;o=-m|b0bo|b1v;-1_ĺ$_;l-foub|‹ ŐmƷƑƑķƕƒѷőu;1;bˆ;7-m|b0bo|b1v‰b|_bm|_;=buv|‰;;ho=Ѵb=;ŐbmŊ |u-ˆ;mo†v 0;mŒ‹Ѵr;mb1bѴѴbm -m7 ];m|-lb1bm Œm Ʒ ƐѶœķ bm|u-ˆ;mo†v 0;mŒ‹Ѵr;mb1bѴѴbmķ];m|-lb1bm-m7ˆ-m1ol‹1bmŒmƷƐœķbm|u-ˆ;mo†v -m|b0bo|b1v mo| 7o1†l;m|;7 Œm Ʒ Ɛœķ ou-Ѵ 1;r_-Ѵ;Šbm Œm Ʒ Ɛœ -m7 ou-Ѵ =Ѵ†1ѴoŠ-1bѴѴbm Œm Ʒ Ɛœőĺ $_; 7†u-|bom o= -7lbmbv|u-|bom ˆ-ub;7 0;|‰;;mƑ-m7ƕ7-‹vŐl;-mƒķl;7b-mƒőĺ=|_;u;l-bmbm];b]_| bm=-m|vķ=o†u‰;u;-7lb||;7|o_ovrb|-Ѵ=oubm|u-ˆ;mo†v-m|b0bo|Ŋ b1vŐ-Œb|_uol‹1bmŒmƷƐœ-m7-m|b0bo|b1vmo|7o1†l;m|;7ŒmƷƒœő 0;|‰;;m Ƒ -m7 Ɣ ‰;;hv o= -]; Ől;-m ƒĺƔķ l;7b-m ƒĺƔőĺ $_; 7†Ŋ u-|bomo=-7lbmbv|u-|bom‰-vѴ;vv|_-mƔ7-‹vŐmƷƑbm=-m|vő-m7 0;|‰;;m Ɣ -m7 ƐƏ 7-‹v Őm Ʒ Ƒ bm=-m|vőĺ $_; bm=-m| ‰_o u;1;bˆ;7 bm|u-ˆ;mo†v-Œb|_uol‹1bm‰-v1om|bm†;7omou-Ѵ-Œb|_uol‹1bm=ou ƒ 7-‹vĺ 77b|bom-ѴѴ‹ķ |‰o bm=-m|v ‰;u; 1om|bm†;7 om ou-Ѵ -m|b0bŊ o|b1v Őmo| 7o1†l;m|;7őķ om; =ou Ɣ 7-‹v -m7 om; =ou lou; |_-m ƐƏ 7-‹vĺ $_;u; ‰;u; =o†u bm=-m|v ‰_o u;1;bˆ;7 ou-Ѵ -m|b0bo|b1v -=|;u |_; =buv| ‰;;h o= Ѵb=; Ő-]; u-m]; ƑŊƓķ l;-m ƒĺѶķ l;7b-m Ɠ‰;;hvőŐ-loŠb1bѴѴbmŒmƷƑœķ1;r_-Ѵ;ŠbmŒmƷƑœőĺ$_;7†u-|bomo= -7lbmbv|u-|bom‰-vƔŊƐƏ7-‹v=ou-ѴѴĺ

ƒĺƐՊ|Պ==;1|o=v;Šomˆ-11bm;u;vromv;v

|ƕlom|_vo=-];ķ=;l-Ѵ;v_-7-Ѵo‰;uv;uoruo|;1|bomu-|;-]-bmv| b01olr-u;7‰b|_l-Ѵ;bm=-m|vŐѵѵѷŒƖƔѷƔƐĺѵѷŊƕƖĺѵѷœˆvѶѵѷ ŒƖƔѷƕƑĺƐѷŊƖƓĺƕѷœĸPƷĺƏƔőĺo‰;ˆ;uķoˆ;u-ѴѴ|_;u;‰;u;mov|-Ŋ |bv|b1-ѴѴ‹vb]mb=b1-m|7b==;u;m1;v0;|‰;;ml-Ѵ;v-m7=;l-Ѵ;vbmv;Ŋ uoruo|;1|bomu-|;v-|ƕouƐƒlom|_vo=-];Ő$-0Ѵ;Ƒ--m7 b]†u;Ƒőĺ

http://doc.rero.ch

=|;u -7f†v|l;m| =ou ru;Ŋvr;1b=b;7 =-1|ouvķ |_; =;l-Ѵ;Ĺl-Ѵ; ! ‰-v0;Ѵo‰om;Őbm7b1-|bm]Ѵo‰;u-ˆ;u-];-m|b0o7‹1om1;m|u-|bomvő bm=;l-Ѵ;v=ou|;|-m†v-m7 Ő$-0Ѵ;Ƒ0-m7 b]†u;Ƒő-|ƕlom|_v o=-];-m7=ou!-|Ɛƒlom|_vo=-];ĺ$_;v;=bm7bm]v‰;u;v|-|bvŊ |b1-ѴѴ‹vb]mb=b1-m|ĺ|Ɛƒlom|_vo=-];ķ-7f†v|;7-ˆ;u-];-m|b0o7‹ 1om1;m|u-|bomv‰;u;v|-|bv|b1-ѴѴ‹vb]mb=b1-m|Ѵ‹_b]_;ubm=;l-Ѵ;v=ou roѴbo |‹r; ƒķ rm;†lo1o11†v v;uo|‹r; ѵ -m7 l;-vѴ;v Ő$-0Ѵ; Ƒ0 -m7 b]†u;Ƒőĺ

ƒĺƑՊ|Պo;==;1|o=7;Ѵbˆ;u‹lo7;om

vaccine responses

|ƕlom|_vo=-];ķv;uoruo|;1|bomu-|;v‰;u;Ѵo‰;ubmbm=-m|v0oum ˆ-]bm-ѴѴ‹|_-mbm|_ov;0oum0‹1-;v-u;-mv;1|bom=ou|_;l-foub|‹o= ˆ-11bm;-m|b];mvĺo‰;ˆ;uķmom;o=|_;v;7b==;u;m1;vu;-1_;7v|-Ŋ |bv|b1-Ѵvb]mb=b1-m1;ĺ|Ɛƒlom|_vo=-];ķ|_;u;‰;u;mo7b==;u;m1;v bmv;uoruo|;1|bomu-|;v0;|‰;;mbm=-m|v0oumˆ-]bm-ѴѴ‹ou0‹1-;v-uŊ ;-mv;1|bomŐ$-0Ѵ;"Ɛ--m7 b]†u;"Ɛőĺ|Ɛƒlom|_vo=-];ķbm=-m|v 0oumˆ-]bm-ѴѴ‹_-7-_b]_;u-ˆ;u-];-m|b0o7‹1om1;m|u-|bom-]-bmv| b0Ő$-0Ѵ;"Ɛ0-m7 b]†u;"Ɛőĺ

ƒĺƒՊ|Պo;==;1|o==;;7bm]l;|_o7om

vaccine responses

| ƕ -m7 Ɛƒ lom|_v o= -];ķ |_;u; ‰;u; mo v|-|bv|b1-ѴѴ‹ vb]mb=b1-m| 7b==;u;m1;v bm v;uoruo|;1|bom u-|;v ou -7f†v|;7 -ˆ;u-]; -m|b0o7‹ 1om1;m|u-|bomv0;|‰;;mbm=-m|v‰_ou;1;bˆ;7ou7b7mo|u;1;bˆ;=ouŊ l†Ѵ-lbѴhbm=buv|=;‰7-‹vo=Ѵb=;ou0;|‰;;mbm=-m|v‰_o‰;u;v|bѴѴ u;1;bˆbm]0u;-v|lbѴh-|Ɛouѵlom|_vo=-];-m7|_ov;‰_o‰;u;mo| Ő$-0Ѵ;v"Ƒ-Ŋ"Ɠ0-m7 b]†u;v"ƑŊ"Ɠőĺ$_;omѴ‹;Š1;r|bom‰-v-v|-Ŋ |bv|b1-ѴѴ‹vb]mb=b1-m|_b]_;u-7f†v|;7-ˆ;u-];-m|b0o7‹1om1;m|u-|bom Őb;ķ-!]u;-|;u|_-mom;ő-]-bmv|rm;†lo1o11†vv;uo|‹r;ƕ -| ƕlom|_vo=-];bmbm=-m|v‰_o7b7mo|u;1;bˆ;=oul†Ѵ-lbѴh7†ubm] |_;=buv|=;‰7-‹vo=Ѵb=;1olr-u;7|o|_ov;‰_o7b7Ő$-0Ѵ;"Ƒ0-m7 b]†u;"Ƒőķ-m7_b]_;u-m|b0o7‹1om1;m|u-|bom=ourm;†lo1o11†vv;Ŋ uo|‹r;ƐƖ -m7;m-|Ɛƒlom|_vo=-];bmbm=-m|v‰_o‰;u;v|bѴѴ u;1;bˆbm]0u;-v|-|ѵlom|_vo=-];Ő$-0Ѵ;v"Ɠ0-m7 b]†u;"Ɠőĺ

ƒĺƓՊ|Պbmbl-Ѵ;==;1|o=bm|u-r-u|†loubm=-m|

antibiotic exposure on vaccine responses

| ƕ -m7 Ɛƒ lom|_v o= -];ķ |_;u; ‰;u; mo 7b==;u;m1;v bm v;uoruoŊ |;1|bomu-|;v0;|‰;;mbm=-m|v‰_ov;lo|_;uv7b7ou7b7mo|u;1;bˆ; -m|b0bo|b1v 7†ubm] 7;Ѵbˆ;u‹Ő$-0Ѵ; "Ɣ- -m7 b]†u; "Ɣőĺ m=-m|v‰_ov; lo|_;u u;1;bˆ;7 bm|u-r-u|†l -m|b0bo|b1v _-7 - vb]mb=b1-m|Ѵ‹ _b]_;u -7f†v|;7 -ˆ;u-]; -m|b0o7‹ 1om1;m|u-|bom -]-bmv| ! -| ƕ -m7 Ɛƒlom|_vo=-];Ő$-0Ѵ;v"Ɣ0-m7 b]†u;"Ɣőĺm|b0bo|b1;Šrov†u;0;Ŋ =ou; |_;bu =buv| uo†|bm;ˆ-11bm-|bom v1_;7†Ѵ;7 -| ѵ‰;;hv o= -]; 7b7 mo| bm=Ѵ†;m1; v;uoruo|;1|bom u-|;v ou -ˆ;u-]; -m|b0o7‹ 1om1;m|u-Ŋ |bomvŐ$-0Ѵ;"ѵ-ķ0-m7 b]†u;"ѵőĺ

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$_bvv|†7‹bv|_;=buv||obmˆ;v|b]-|;|_;;==;1|o=l†Ѵ|brѴ;7b==;u;m| ;-uѴ‹ŊѴb=; =-1|ouv om -m|b0o7‹ u;vromv;v |o uo†|bm; ˆ-11bm-|bomv bm bm=-m1‹ĺ ); =o†m7 |_-| bm=-m| 0boѴo]b1-Ѵ v;Š _-7 -m blr-1| om u;Ŋ vromv;v0†|7;Ѵbˆ;u‹lo7;ķ=;;7bm]l;|_o7ķbm|u-r-u|†l-m|b0bo|b1v -m7-m|b0bo|b1;Šrov†u;0;=ou;|_;=buv|uo†|bm;bll†mbv-|bom7b7mo|ĺ

†u=bm7bm]|_-|=;l-Ѵ;v_-7Ѵo‰;u-m|b0o7‹u;vromv;v-]-bmv| |;|-m†v-m7_b]_;uu;vromv;v-]-bmv|roѴboŐ|‹r;ƒőbv1omvbv|;m|‰b|_ ru;ˆbo†v v|†7b;v bm -7†Ѵ|vĺƖŊƐƐ u;ˆbo†v v|†7b;v _-ˆ; -Ѵvo u;rou|;7 =;l-Ѵ;-7†Ѵ|v|o_-ˆ;_b]_;u-m|b0o7‹u;vromv;v|o7;m]†;ķ;rķ ;rķu-0b;vķvl-ѴѴroŠ-m7|ubˆ-Ѵ;m|bm=Ѵ†;mŒ-ˆ-11bm;vķ‰_bѴ;l-Ѵ; -7†Ѵ|v _-ˆ; 0;;m u;rou|;7 |o _-ˆ; _b]_;u u;vromv;v |o 7br_|_;ub- -m71omf†]-|;7l;mbm]o1o11†vˆ-11bm;vĺ2$_;omѴ‹v|†7b;v‰_b1_ _-ˆ;ru;ˆbo†vѴ‹0;;m7om;bmbm=-m|vu;rou|;7_b]_;u-m|b0o7‹u;Ŋ vromv;vbm=;l-Ѵ;v|o;rķb0-m7(Ɛƒĺ2vb7;=uol-_b]_;u -ˆ;u-];-m|b0o7‹1om1;m|u-|bombm=;l-Ѵ;v-]-bmv|om;rm;†lo1o1Ŋ 1-Ѵv;uo|‹r;Őѵőķ‰;7b7mo|=bm7v;Š7b==;u;m1;vbm|_;u;vromv;|o rm;†lo1o11-Ѵˆ-11bm-|bomĺ$_bv1om|u-v|v‰b|_v|†7b;vbm-7†Ѵ|vķbm   & !   Ɛ Պ ";Ѵ;1|bomo=r-u|b1br-m|vĺŖƒƒr-u|b1br-m|v_-7|_;bu 0Ѵoo7-m-Ѵ‹v;7-|0o|_ƕ-m7Ɛƒloo=-]; Total participants n = 471

Twin of another participant n = 7 Not vaccinated according to schedule n = 4

Vaccine records not available n = 1 No parental consent n = 5

n = 454

Response to 12-mo vaccinations n = 144

Blood not taken in correct time frame after vaccination n = 89

n = 365

Blood taken at13 mo of age* Blood taken at7 mo of age*

Response to 6-mo vaccinations n = 91

Response to 6-mo vaccinations n = 307

Female n = 48 Vaginal delivery

n = 56 Formula milk in hospital

n = 25 Breastfed at 1 month n = 80 Breastfed at 6 months n = 71 Intrapartum antibiotics n = 21 Antibiotics < 6 weeks n = 4 Male n = 43 Caesarean section n = 35 No formula milk in hospital

n = 66 Not breastfed at 1 month

n = 11 Not breastfed at 6 months

n = 20 No intrapartum antibiotics n = 70 No antibiotics < 6 weeks n = 87 Female n = 73 Vaginal delivery n = 91 Formula milk in hospital

n = 37 Breastfed at 1 m n = 119 Breastfed at 6 months n = 107 Intrapartum antibiotics n = 32 Antibiotics < 6 weeks n = 13 Male n = 71 Caesarean section n = 53 No formula milk in hospital

n = 107 Not breastfed at 1 m

n = 25 Not breastfed at 6 months

n = 37 No intrapartum antibiotics n = 112 No antibiotics < 6 weeks n = 131 Female n = 158 Vaginal delivery n = 192 Formula milk in hospital

n = 84 Breastfed at 1 month n = 251 Breastfed at 6 months n = 219 Intrapartum antibiotics n = 62 Antibiotics < 6 weeks n = 29 Male n = 149 Caesarean section n = 115 No formula milk in hospital

n = 223 Not breastfed at 1 month

n = 56 Not breastfed at 6 months

n = 88 No intrapartum antibiotics n = 245 No antibiotics < 6 weeks n = 278

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$    ƐՊ  _ - u-1| ; ub v| b1 vo=v |† 7 ‹r -u| b1 br -m |v $o |-Ѵ1 o _ o u| Sa m pl es a t 7 m o of a ge f or an tibodies Sa m pl es a t 13 m o of a ge f or persist enc e o f an tibodi es Sa m pl es a t 13 m o of a ge f or an tibodies (n = 3 65) n (%) o r m ed ia n ( IQ R ) to p ri m ar y c ou rs e of v ac ci ne s e nd in g a t 6 m o of a ge to 12 -m o v acci ne s (n = 91 ) n (%) o r m ed ia n ( IQ R ) (n = 3 07 ) n (% o r I Q R ) (n = 1 4 4) n (% o r I Q R ) " ; ŠŐl -Ѵ;ő Ɛ ƕ ƖŐ Ɠ Ɩ ő Ɠ ƒŐ Ɠ ƕ ő Ɛ Ɠ ƖŐ Ɠ Ɩ ő ƕ ƐŐ Ɠ Ɩ ő  ; v| -| bo m - Ѵ-] ;Չ h ő ƒ Ɩ ĺƒŐƒ Ѷ ĺƓ ŊƓ Ə ĺƓ ő ƒ Ɩ ĺƔŐƒ Ѷ ĺѵ ŊƓ Ə ĺƔ ő ƒ Ɩ ĺƒŐƒ Ѷ ĺƓ ŊƓƏ ĺƒ ő ƒ Ɩ ĺƑ Ő ƒ Ѷ ĺƓ ŊƓƏ ĺƓ ő  bu |_‰ ; b] _ |Ő h ] ő ƒ ĺƓ ƔŐƒ ĺƐ ƒ Ŋƒ ĺƕ ѵ ő ƒ ĺƓ ѶŐƒ ĺƐ Ə Ŋƒ ĺƕѶ ő ƒ ĺƓ ƔŐƒ ĺƐ ƒ Ŋƒ ĺƕ ѵ ő ƒ ĺƓ ƐŐƒ ĺƐ ƒ Ŋƒ ĺѵ ƕ ő  -; v-u; -mv ; 1 |b o m Ɛ ƒ ѵŐƒƕ ő ƒƔŐƒ Ѷ ő Ɛ Ɛ ƔŐƒƕ ő Ɣ ƒŐƒƕ ő ! ; 1; bˆ ; 7= o ul † Ѵ-l bѴhb m_ o vr b| -Ѵb m= bu v|‰ ; ; ho=Ѵ b= ; Ɛ Ə ƏŐ Ƒ ƕ ő Ƒ ƔŐ Ƒ ƕ ő Ѷ ƓŐ Ƒ ƕ ő ƒ ƕŐ Ƒ ѵ ő "| bѴѴu ; 1; bˆ bm ]0 u; -v |-|Ɛl oo=-] ; ƒ Ə ƑŐ Ѷ ƒ ő Ѷ ƏŐ Ѷ Ѷ ő Ƒ Ɣ ƐŐ ѶƑő Ɛ Ɛ Ɩ Ő Ѷ ƒ ő "| bѴѴu ; 1; bˆ bm ]0 u; -v |-|ѵl oo=-] ; Ƒ ѵ ƒŐ ƕƑő ƕ ƐŐ ƕѶ ő Ƒ Ɛ ƖŐ ƕ Ɛ ő Ɛ Ə ƕ Ő ƕ Ɠ ő  m |b 0 bo |b 1v7 † ub m ]-7 l bv vb o m= o u7 ; Ѵbˆ ; u‹ m |u -r -u| † l-m |b 0 bo |b 1v ƕƏŐ Ɛ Ɩ ő Ƒ ƐŐ Ƒƒ ő ѵ ƑŐ Ƒ Ə ő ƒƑŐ Ƒ Ƒ ő  m |b 0 bo |b 1v0 ; =o u;= bu v|ˆ -11 bm -| bo m ƒ ƏŐ Ѷ ő ƓŐ Ɠő Ƒ ƖŐ Ɩ ő Ɛ ƒŐ Ɩ ő    Ŋˆ -11 bm -| ; 7 Ɛ ƖѶŐ Ɣ Ɠ ő Ɠ ƔŐ Ɠ Ɩ ő Ɛ ѵ ѵŐ Ɣ Ɠ ő ƕ ѵŐ Ɣ ƒ ő  -| ; um -Ѵ7 $ r -ˆ -11 bm -| bo mb mr u; ] m -m 1‹ Ɛ ƕ ƓŐ Ɠ Ѷ ő Ɠ ѵŐ Ɣ Ɛ ő Ɛ Ɠ ѵŐ Ɠ Ѷ ő ѵ ƕ Ő Ɠ ƕ ő  -| ; um -Ѵb m =Ѵ † ; m Œ-ˆ -11 bm -| bo mb mr u; ] m -m 1‹ Ƒ Ə ѶŐ Ɣƕ ő Ɣ ƔŐ ѵ Ə ő Ɛ ƕ ƐŐ Ɣ ѵ ő Ѷ ƓŐ Ɣ Ѷ ő  ] ;-|u o † |b m ;ˆ -11 bm -| bo mŐ 7 ő ѵ Ŋ‰ hˆ -11 bm ; v Ɠ ƔŐ Ɠ ƒ ŊƓ Ɩ Ɠ ő a Ɠ ƔŐ Ɠ ƒ ŊƓ Ѷ ő a Ɠ ƔŐ Ɠ ƒ ŊƓ Ɩ ő Ɠ ƔŐ Ɠ ƒ ŊƓ Ѷ ő Ɠ Ŋl oˆ -11 bm ; v Ɛ Ƒ ƔŐ Ɛ Ƒ Ə ŊƐ ƒ Ɛő Ɛ Ƒ ƒŐ Ɛ Ɛ ƕ ŊƐ Ƒ ƕ ő Ɛ Ƒ ƔŐ Ɛ Ƒ Ɛ ŊƐ ƒ Ƒő Ɛ Ƒ ƓŐ Ɛ Ƒ Ə ŊƐ ƒ Ɛő ѵ Ŋl oˆ -11 bm ; v Ɛ Ɩ ƏŐ Ɛ Ѷ Ɠ ŊƑ Ə Ƒ ő Ɛ Ѷ ƕŐ Ɛ Ѷ Ɛ ŊƐ Ɩ ƒ ő Ɛ ƖƐŐ Ɛ Ѷ Ɣ ŊƑ Ə Ɠő Ɛ Ɩ ƏŐ Ɛ Ѷ Ɣ ŊƑ Ə Ɛő Ɛ Ƒ Ŋl oˆ -11 bm ; v ƒ ƕ ѵŐƒ ѵ Ɩ Ŋƒ Ѷ ƒ ő –– ƒƕ ѵŐƒ ѵ Ɩ Ŋƒ Ѷ ƒ ő m |; uˆ -Ѵ0 ; |‰ ; ; mŐ 7 ő ѵ Ŋl oˆ -11 bm ; v-m 7ƕ Ŋl o0 Ѵo o 7v -l r Ѵ; – ƑѶŐ Ƒ Ɛ Ŋƒƕ ő –– ѵ Ŋl oˆ -11 bm ; v-m 7Ɛ ƒ Ŋl o0 Ѵo o 7v -l r Ѵ; –– Ƒ Ə ƖŐ Ɛ Ɩ Ə ŊƑ Ƒ Ɠő – Ɛ Ƒ Ŋl oˆ -11 bm ; v-m 7Ɛ ƒ Ŋl o0 Ѵo o 7v -l r Ѵ; –– – ƑѶŐ Ƒ Ƒ Ŋƒ ѵ ő  ] ;-|0 Ѵo o 7v -l r Ѵbm ]Ő 7 ő – Ƒ Ɛ ѶŐ Ƒ Ə Ѷ ŊƑ Ƒ ƕ ő Ɠ Ə ƏŐƒ Ѷ Ɩ ŊƓ Ɛ Ѷ ő Ɠ Ə ѵŐƒ Ɩ ƕ ŊƓ Ɛ Ɠ ő  0 0 u; ˆ b-|b o m vĹ  ķ -1b ѴѴ; -Ѵl ; || ; Ŋ † ࣐ ub m ĸ7 $ r -ķ7 br _ |_ ; ub -Ŋ |; |-m † vŊ-1; ѴѴ† Ѵ-ur ; u| † vv bvˆ -11 bm ; ĺ a ] ;= o uo m ;r -u| b1 br -m |m o |-ˆ -b Ѵ-0 Ѵ; ĺ

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$    ƑՊ Ő-ő" ; uo r uo |; 1| bo mu -| ; v- |ƕ-m 7Ɛ ƒl oo=-];b m= ; l -Ѵ ;-m 7l -Ѵ;b m= -m |v ĺŐ 0 ő ; o l ; |u b1l ; - m-m |b 0 o 7 ‹1 o m 1; m |u -| bo m vŐ   vő-m 7]; o l ; |u b1l ; - m-m |b 0 o 7 ‹u -| bo vŐ  ! vő-|ƕ -m 7Ɛ ƒl oo=-];b m= ; l -Ѵ ;-m 7l -Ѵ ;b m= -m |v (a) Vacc in e an tig en Pro te ctiv e co rr el ate A nt ib od ie s t o p ri m ar y c ou rs e of v ac ci ne s e nd in g a t 6 m o of a ge m ea su re d a t 7 m o of a ge A nt ib od ie s t o p ri m ar y c ou rs e of v ac ci ne s e nd in g a t 6 m o of a ge m ea su re d a t 13 m o of a ge Fe m al e (n = 4 8) Male (n = 4 3) Di ff erenc e % (9 5% C I) $ ‰ oŊ vb7;7  P-value Fe m al e (n = 15 8) Male (n = 1 49 ) Di ff erenc e % (9 5% C I) $ ‰ oŊ vb7;7  P-value % (n) ; (9 5% C I) % (n) ; (9 5% C I) % (n) ; (9 5% C I) % (n) ; (9 5% C I) br_ |_;ub -Ə ĺƐ  & ņl a Ɩ ƕĺ ƖŐ Ɠ ƕ őĸŐ Ѷ Ѷ ĺƖ ķƖ Ɩ ĺƖ ő Ɩ Ɣ ĺƒŐ Ɠ Ɛ őĸŐ Ѷ Ɠ ĺƐ ķƖ Ɩ ĺƓő Ƒ ĺѵŐ ƴ ѵ ĺƖ ķƐ ƒ ĺƕ ő .6 0 ƖѶ ĺƕŐ Ɛ Ɣ ѵ őĸŐ Ɩ Ɣ ĺƔ ķƖ Ɩ ĺѶ ő ƖѶ ĺƏŐ Ɛ Ɠ ѵ őĸŐ Ɩ Ɠ ĺƑ ķƖ Ɩ ĺѵ ő Ə ĺƕŐ ƴ Ƒ ĺƕ ķƓ ĺѵ ő .68 $; |-m † v Ə ĺƐ  & ņl  a Ɛ Ə ƏŐ Ɠ Ѷ őĸŐ Ɩ Ƒ ĺѵ ķƐ Ə Ə ő Ɛ Ə ƏŐ Ɠ ƒ őĸŐ ƖƐ ĺѶ ķƐ Ə Ə ő ƏŐ ƴƕ ĺƔ ķѶ ĺƒ ő – Ɛ Ə ƏŐ ѶƔ őĸŐ Ɩ ѵ ĺѶ ķƐ Ə Ə ő b Ɛ Ə ƏŐ ƕѶ őĸŐ Ɩ Ɣ ĺƓ ķƐ Ə Ə ő b ƏŐ ƴ Ɠ ĺƒ ķƓ ĺƕ ő b –  $ Ƒ Ɣ & ņl  Ѷ Ɩ ĺѵŐ Ɠ ƒ őĸŐ ƕ ƕĺ ƒ ķƖ ѵ ĺƔ ő Ɩ Ə ĺƕŐƒ Ɩ őĸŐ ƕ ƕĺ Ɩ ķƖ ƕĺ Ɠő ƴƐ ĺƐŐ ƴƐ Ɠ ĺƓ ķƐ Ƒ ĺƕ ő 1 ƑѶ ĺƔŐ Ɠ Ɣ őĸŐ Ƒ Ɛ ĺѵ ķƒ ѵ ĺƑő ƒ Ɛ ĺƔŐ Ɠ ƕ őĸŐ Ƒ Ɠ ĺƑ ķƒ Ɩ ĺƕ ő ƴ ƒ ĺƐŐ ƴƐ ƒ ĺƒ ķƕ ĺƑ ő .6 2  b0 Ə ĺƐ Ɣ੿ ] ņl  ѵ ѵ ĺƕŐƒƑő ĸŐ Ɣ Ɛ ĺѵ ķƕƖ ĺѵ ő Ѷ ѵ ĺƏŐƒƕ őĸŐ ƕƑ ĺƐ ķƖ Ɠ ĺƕ ő ƴƐ Ɩ ĺƓŐ ƴ ƒ ѵ ĺƏ ķƴ Ɛ ĺƕ ő ĺƏ Ɣ Ѷ Ə ĺƏŐ ѵ Ѷ őŐ ѵ Ɩ ĺƖ ķѶ ƕĺ Ɩ ő b ƕƒ ĺƐŐ Ɣƕ őĸŐ ѵ Ɛ ĺѶ ķѶƑ ĺƔ ő b ѵĺ Ɩ Őƴ ѵĺ Ɛ ķƑ Əĺ Ɛ ő b .3 6 b  o Ѵbo| ‹ r ;Ɛ Ə ĺƑƒ & ņl  Ɛ Ə ƏŐ Ɠ Ѷ őĸŐ Ɩ Ƒ ĺѵ ķƐ Ə Ə ő Ɛ Ə ƏŐ Ɠ ƒ őĸŐ ƖƐ ĺѶ ķƐ Ə Ə ő ƏŐ ƴƕ ĺƔ ķѶ ĺƒ ő – Ɛ Ə ƏŐ Ɛ Ɣ Ѷ őĸŐ Ɩ ƕĺƕ ķƐ Ə Ə ő Ɛ Ə ƏŐ Ɛ Ɠ Ɩ őĸŐ Ɩ ƕĺ ѵ ķƐ Ə Ə ő ƏŐ ƴ Ƒ ĺƓ ķƑ ĺƔ ő –  o Ѵbo| ‹ r ;Ƒ Ə ĺƑ Ɩ & ņl  Ɛ Ə ƏŐ Ɠ Ѷ őĸŐ Ɩ Ƒ ĺѵ ķƐ Ə Ə ő Ɛ Ə ƏŐ Ɠ ƒ őĸŐ ƖƐ ĺѶ ķƐ Ə Ə ő ƏŐ ƴƕ ĺƔ ķѶ ĺƒ ő 1 Ɛ Ə ƏŐ Ɛ Ɣ Ѷ őĸŐ Ɩ ƕĺƕ ķƐ Ə Ə ő Ɩ Ɩ ĺƒŐ Ɛ Ɠ Ѷ őĸŐ Ɩ ѵ ĺƒ ķƐ Ə Ə ő Ə ĺƕŐ ƴƐ ĺƕ ķƒ ĺƕ ő .4 9  o Ѵbo| ‹ r ;ƒ Ə ĺƐ Ƒ & ņl  Ɛ Ə ƏŐ Ɠ Ѷ őĸŐ Ɩ Ƒ ĺѵ ķƐ Ə Ə ő Ɛ Ə ƏŐ Ɠ ƒ őĸŐ ƖƐ ĺѶ ķƐ Ə Ə ő ƏŐ ƴƕ ĺƔ ĸѶ ĺƒ ő – Ɛ Ə ƏŐ Ɛ Ɣ Ѷ őĸŐ Ɩ ƕĺƕ ķƐ Ə Ə ő Ɛ Ə ƏŐ Ɛ Ɠ Ɩ őĸŐ Ɩ ƕĺ ѵ ķƐ Ə Ə ő ƏŐ ƴ Ƒ ĺƓ ķƑ ĺƔ ő –  mƐ Ə ĺƒƔ੿ ] ņl  Ɩ Ɣ ĺѶŐ Ɠ ѵ őĸŐ ѶƔ ĺƕ ķƖ Ɩ ĺƔ ő Ɩ ƕĺƕŐ Ɠ Ƒ őĸŐ Ѷ ƕĺƕ ķƖ Ɩ ĺƖ ő ƴƐ ĺѶŐ ƴƐ Ƒ ĺƐ ķѶ ĺƓ ő 1 Ɩ Ƒ ĺƓŐ Ɛ Ɠ ѵ őĸŐ Ѷ ƕĺ Ɛ ķƖ ѵ ĺƏ ő Ɩ Ɣ ĺƒŐ Ɛ Ɠ Ƒő ĸŐ Ɩ Ə ĺѵ ķƖѶ ĺƐ ő ƴ Ƒ ĺƖŐ ƴѶ ĺƕ ķƑ ĺƕ őĺ ƒ Ɣ  mƒ Ə ĺƒƔ੿ ] ņl  Ɩ ƕĺ ƖŐ Ɠ ƕ őĸŐ Ѷ Ѷ ĺƖ ķƖ Ɩ ĺƖ ő Ɛ Ə ƏŐ Ɠ ƒ őĸŐ ƖƐ ĺѶ ķƐ Ə Ə ő ƴ Ƒ ĺƐ Őƴ Ɛ Ɛ ĺƏ ķѵ ĺƒ ő 1 ƕƏ ĺƒ ŐƐ Ɛ Ɛő ĸŐ ѵƑ ĺƔ ķƕ ƕĺ ƒ ő ѵ Ɩ ĺƐŐ Ɛ Ə ƒ őĸŐ ѵ Ɛ ĺƏ ķƕ ѵ ĺƓő Ɛ ĺƐŐ ƴ Ɩ ĺƐ ķƐ Ɛ ĺƓ ő .9 0  mƓ Ə ĺƒƔ੿ ] ņl  ѵ ѵ ĺƕŐƒƑő ĸŐ Ɣ Ɛ ĺѵ ķƕƖ ĺѵ ő ƕ Ƒ ĺƐŐƒ Ɛő ĸŐ Ɣ ѵ ĺƒ ķѶ Ɠ ĺƕ ő ƴ Ɣ ĺƓŐ ƴ Ƒ Ɠ ĺƏ ķƐ ƒ ĺѶ ő ĺѵ Ɣ Ƒ Ɠ ĺƐŐƒ Ѷ őĸŐ Ɛ ƕĺ ѵ ķƒ Ɛ ĺƔ ő Ƒ Ɛ ĺƔŐƒƑő ĸŐ ƐƔ ĺƑ ķƑѶ ĺƖ ő Ƒ ĺѵŐ ƴ ѵ ĺƖ ķƐ Ƒ ĺƏ ő .68  mƔ Ə ĺƒƔ੿ ] ņl  Ɩ Ɣ ĺѶŐ Ɠ ѵ őĸŐ Ѷ ѵ ĺƕ ķƖ Ɩ ĺƔ ő Ɛ Ə ƏŐ Ɠ ƒ őĸŐ ѶƔ ĺѵ ķƖ Ɩ ĺƔ ő ƴ Ɠ ĺƑ Őƴ Ɛ Ɠ ĺƐ ķƓ ĺƒ ő ĺƔ Ə Ѷ Ɩ ĺƑ ŐƐ Ɠ Ɛő ĸŐ Ѷ ƒ ĺƒ ķƖ ƒ ĺѵ ő Ѷ Ɠ ĺѵŐ Ɛ Ƒ ѵ őĸŐ ƕ ƕĺƕ ķƖ Ə ĺƏ ő Ɠ ĺƕŐ ƴ Ƒ ĺƖ ķƐ Ƒ ĺƔ ő .2 4  m ѵ  Ə ĺƒ Ɣ੿ ] ņl  Ɩ ƕĺ Ɩ Ő Ɠ ƕ őĸŐ Ѷ Ѷ ĺƖ ķƖ Ɩ ĺƖ ő Ɩ ƕĺƕŐ Ɠ Ƒ őĸŐ Ѷ ƕĺƕ ķƖ Ɩ ĺƖ ő Ə ĺƑŐ ƴѶ ĺƖ ķƐ Ə ĺƒ ő 1 Ѷ Ѷ ĺƏŐ Ɛ ƒ Ɩ őĸŐ Ѷ Ɛ ĺƖ ķƖ Ƒ ĺѵ ő ѶƔ ĺƑŐ Ɛ Ƒ ƕ őĸŐ ƕѶ ĺƔ ķƖ Ə ĺƔ ő Ƒ ĺƕŐ ƴ Ɣ ĺƏ ķƐ Ə ĺѵ őĺ Ɣ Ə  mѵ  Ə ĺƒ Ɣ੿ ] ņl  Ѷ ƒ ĺƒŐ Ɠ Ə őĸŐ ѵ Ɩ ĺѶ ķƖ Ƒ ĺƔ ő Ɩ Ɣ ĺƒŐ Ɠ Ɛ őĸŐ Ѷ Ɠ ĺƑ ķƖ Ɩ ĺƓő ƴƐ Ƒĺ Ə Őƴ Ƒ Ɣ ĺѶķ Ɛ ĺƐ ő .10 ѵ Ѷ ĺƓŐ Ɛ Ə Ѷ őĸŐ ѵ Ə ĺƔ ķƕ Ɣ ĺƔ ő Ɣ Ɩ ĺƕŐ Ѷ Ɩ őĸŐ Ɣ Ɛ ĺƓ ķѵ ƕĺ ƕ ő Ѷ ĺѵŐ ƴ Ƒ ĺƐ ķƐ Ɩ ĺƑő .1 2  mƕ Ə ĺƒƔ੿ ] ņl  Ɛ Ə ƏŐ Ɠ Ѷ őĸŐ Ɩ Ƒ ĺѵ ķƐ Ə Ə ő Ɛ Ə ƏŐ Ɠ ƒ őĸŐ ƖƐ ĺѶ ķƐ Ə Ə ő ƏŐ ƴƕ ĺƔ ķѶ ĺƒ ő – Ɩ Ɩ ĺƓŐ Ɛ Ɣ ƕ őĸŐ Ɩ ѵ ĺƔ ķƐ Ə Ə ő Ɩ Ɩ ĺƒŐ Ɛ Ɠ Ѷ őĸŐ Ɩ ѵ ĺƒ ķƐ Ə Ə ő ƏŐ ƴ Ƒ ĺƖ ķƒ ĺƐ ő 1  mƖ ( Ə ĺƒ Ɣ੿ ] ņl  Ɩ ƕĺ ƖŐ Ɠ ƕ őĸŐ Ѷ Ѷ ĺƖ ķƖ Ɩ ĺƖ ő Ɩ ƕĺƕŐ Ɠ Ƒ őĸŐ Ѷ ƕĺƕ ķƖ Ɩ ĺƖ ő Ə ĺƑŐ ƴѶ ĺƖ ķƐ Ə ĺƑő 1 ƕƖ ĺƐŐ Ɛ Ƒ Ɣ őĸŐ ƕ Ɛ ĺƖ ķѶƔ ĺƑ ő ƕ Ƒ ĺƔŐ Ɛ Ə Ѷ őĸŐ ѵ Ɠ ĺѵ ķƕƖ ĺƔ ő ѵ ĺѵŐ ƴ ƒ ĺƏ ķƐ ѵ ĺƑ ő .1 8  mƐ Ɠ Ə ĺƒ Ɣ੿ ] ņl  ƖƐ ĺƕŐ Ɠ Ɠ őĸŐ Ѷ Ə ĺƏ ķƖ ƕĺ ƕ ő Ɩ Ə ĺƕŐƒ Ɩ őĸŐ ƕ ƕĺ Ѷ ķƖ ƕĺ Ɠő Ɛ ĺƏŐ ƴƐ Ɛ ĺѶ ķƐ Ɠ ĺѵ ő 1 Ѷ Ɠ ĺѶŐ Ɛ ƒ Ɠő ĸŐ ƕѶ ĺƑ ķƖ Ə ĺƏ ő Ѷ ƕĺ ƖŐ Ɛ ƒ Ɛő ĸŐ Ѷ Ɛ ĺƑ ķƖ Ƒ ĺƒ ő ƴ ƒ ĺƐŐ ƴƐ Ə ĺƖ ķƓ ĺƕő ĺƔ Ɛ  mƐ Ѷ  Ə ĺƒƔ੿ ] ņl  Ɩ Ɣ ĺѶŐ Ɠ ѵ őĸŐ ѶƔ ĺƕ ķƖ Ɩ ĺƔ ő Ɩ Ɣ ĺƒŐ Ɠ Ɛ őĸŐ Ѷ Ɠ ĺƑ ķƖ Ɩ ĺƓő Ə ĺƔŐ ƴƐ Ə ĺƏ ķƐ Ɛ ĺƖ ő 1 ƕѶ ĺƔŐ Ɛ Ƒ Ɠő ĸŐ ƕ Ɛ ĺƑ ķѶ Ɠ ĺѵ ő ƕ Ɣ ĺƑŐ Ɛ Ɛ Ƒő ĸŐ ѵ ƕĺ Ɠ ķѶ Ɛ ĺƖ ő ƒ ĺƒŐ ƴ ѵ ĺƑ ķƐ Ƒ ĺѶ őĺ Ɣ Ə  mƐ Ɩ  Ə ĺƒƔ੿ ] ņl  Ɩƒ ĺѶ Ő Ɠ Ɣ őĸŐ ѶƑ ĺѶ ķƖѶ ĺƕ ő Ɩ ƒ ĺƏŐ Ɠ Ə őĸŐ Ѷ Ə ĺƖ ķƖѶ ĺƔ ő Ə ĺƕŐ ƴƐ Ɛ ķƐ ƒ ĺƒ ő 1 Ɠ ƕĺ ƔŐ ƕ Ɣ őĸŐƒ Ɩ ĺƔ ķƔ Ɣ ĺѵ ő Ɣ Ƒ ĺƒŐ ƕѶ őĸŐ Ɠ Ɠ ĺƏ ķѵ Ə ĺѵ ő ƴ Ɠ ĺƖŐ ƴƐ Ɣ ĺƖ ķѵ ĺƒ ő .4 2  mƐ Ɩ Ə ĺƒƔ੿ ] ņl  Ɛ Ə ƏŐ Ɠ ѵ őĸŐ Ɩ Ƒ ĺѵ ķƐ Ə Ə ő Ɛ Ə ƏŐ Ɠ ƒ őĸŐ ƖƐ ĺѶ ķƐ Ə Ə ő ƏŐ ƴƕ ĺƔ ĸ Ѷĺƒ ő – ƖѶ ĺƕŐ Ɛ Ɣ ѵ őĸŐ Ɩ Ɣ ĺƔ ķƖ Ɩ ĺѶ ő Ɛ Ə ƏŐ Ɛ Ɠ Ɩ őĸŐ Ɩ ƕĺ ѵ ķƐ Ə Ə ő ƴƐ ĺƒŐ ƴ Ɠ ĺƔ ķƐ ĺƒ ő ĺƔƏ  mƑƒ Ə ĺƒƔ੿ ] ņl  ƖƐ ĺƕŐ Ɠ Ɠ őĸŐ Ѷ Ə ĺƏ ķƖ ƕĺ ƕ ő Ɩ ƔŐ Ɠ Ɛ őĸŐ Ѷ Ɠ ĺƑ ķƖ Ɩ ĺƓő ƴ ƒ ĺƕŐ ƴƐ Ɣ ĺƕ ķѶ ĺƒ ő .68 ѵƑ ĺƕŐ Ɩ Ɩ őĸŐ Ɣ Ɠ ĺѵ ķƕƏ ĺƑ ő Ɣ Ɩ ĺƕŐ Ѷ Ɩ őĸŐ Ɣ Ɛ ĺƓ ķѵ ƕĺ ƕ ő Ƒ ĺƖŐ ƴѶ ĺƏ ķƐ ƒ ĺѶ ő .6 4 Va cc in e an tig en Pro te ctiv e co rr el ate A nt ib od ie s t o 1 2-m o v ac ci ne s m ea su re d 13 m o of a ge Fe m al e (n = 73 ) M al e (n = 7 1) D if fe re nc e % (9 5% C I) $ ‰ oŊ vb7;7  P-value % (n) ; (9 5% C I) % (n) ; (9 5% C I)  ; -v Ѵ; v Ə ĺƐ Ƒ & ņl  Ɛ Ə ƏŐ ƕƒ őĸŐ Ɩ Ɣ ĺƐ ķƐ Ə Ə ő Ɩ Ɣ ĺѶŐ ѵ Ѷ őĸŐ Ѷ Ѷ ĺƐ ķƖ Ɩ ĺƐő Ɠ ĺƑŐ ƴ Ə ĺƖ ķƐ Ɛ ĺƕ ő .1 2  † l r v Ɠ Ɣ & ņl  Ɣ Ѷ ĺƖŐ Ɠ ƒ őĸŐ Ɠ ѵ ĺѶ ķƕƏ ĺƒ ő ѵ Ƒ ĺƏŐ Ɠ Ɠ őĸŐ Ɠ Ɩ ĺƕ ķƕƒ ĺƑ ő ƴ ƒ ĺƐ Őƴ Ɛ Ѷ ĺѶ ķƐ Ƒ ĺƖ ő .7 4 Ru be lla Ɛ Ə & ņl  ƖƐ ĺѶŐ ѵ ƕ őĸŐ Ѷ ƒ ĺƏ ķƖ ѵ ĺƖ ő Ѷ Ɛ ĺƕŐ Ɣ Ѷ őĸŐ ƕƏ ĺƕ ķѶ Ɩ ĺƖ ő Ɛ Ə ĺƐŐ ƴƐ ĺƐ ķƑ Ɛ ĺѶ ő .09 ;m Ƒ ੿ ] ņl Ɛ Ə ƏŐ ƕƒ őĸŐ Ɩ Ɣ ĺƐ ķƐ Ə Ə ő Ɩ Ѷ ĺѵŐ ƕƏ őĸŐ Ɩ Ƒ ĺƓ ķƐ Ə Ə ő Ɛ ĺƓŐ ƴ ƒ ĺƕ ķƕ ĺѵ ő .4 9 b0 Əĺ Ɛ Ɣ ੿ ] ņl ƖѶ ĺѵŐ ƕƑő ĸŐ Ɩ Ƒ ĺѵ ķƐ Ə Ə ő Ɩ Ѷ ĺѵŐ ƕƏ őĸŐ Ɩ Ƒ ĺƔ ķƐ Ə Ə ő ƏŐ ƴ ѵ ĺƐ ķѵ ĺƓ ő 1 $ ; |-m†v ƏĺƏ Ɛ & ņl  Ɛ Ə ƏŐ ƕƒ őĸŐ Ɩ Ɣ ĺƐ ķƐ Ə Ə ő Ɛ Ə ƏŐ ƕ Ɛ őĸŐ Ɩ Ɠ ĺƒ ķƐ Ə Ə ő ƏŐ ƴ Ɣ ĺƏ ķƔ ĺƐ ő – Ő o m |b m † ; vő

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(b ) Va cc in e an tig en A nt ib od ie s t o p ri m ar y c ou rs e of v ac ci ne s e nd in g a t 6 m o of a ge m ea su re d a t 7 m o of a ge A nt ib od ie s t o p ri m ar y c ou rs e of v ac ci ne s e nd in g a t 6 m o of a ge m ea su re d a t 13 m o of a ge Fe m al e (n = 4 8) M al e (n = 4 3) &m-7f†v |; 7  GM R (9 5% C I) $ ‰ oŊ vb7;7  P-value 7f†v |; 7 e GM R (9 5% C I) $ ‰ oŊ vb7;7  P-value Fe m al e (n = 1 58 ) Male (n = 1 49 ) &m-7f†v |; 7  GM R (9 5% C I) $ ‰ oŊ vb7;7  P-value 7f†v |; 7 f GM R (9 5% C I) $ ‰ oŊ vb7;7  P-value G M C (9 5% C I) G M C (9 5% C I) G M C (9 5% C I) G M C (9 5% C I) br_ |_;ub -c 0.38 ŐƏ ĺƒ Ə ķƏ ĺƓ Ѷ ő 0. 41 ŐƏ ĺƒ ƒ ķƏ ĺƔ Ƒő 0. 92 ŐƏ ĺѵ ƕķƐ ĺƑ ƕ ő .6 1 0. 98 _ŐƏĺƕƑ ķƐ ĺƒ Ƒő .8 8 0.0 8 ŐƏĺƏ ƕķ ƏĺƏƖ ő 0.0 8 ŐƏĺƏѵ ķƏĺƏƖ ő ƐĺƏƔ  ŐƏ ĺѶ ƒ ķƐ ĺƒ Ƒő .6 9 1. 12 ŐƏ ĺƖ Ɛ ķƐ ĺƒ Ѷ ő .2 9 $; |-m † v c 0. 98 ŐƏĺ Ѷ Ƒ ķƐĺ Ɛ Ѷ ő 1. 27 ŐƐ ĺƏ Ɛ ķƐ ĺѵ Ə ő 0. 77 ŐƏ ĺƔ Ѷ ķƐ ĺƏ ƒ ő .0 8 0. 72 _(0.5 4, 0. 97 ) .03 0. 41 ŐƏ ĺƒ Ƒ ķƏ ĺƔ Ƒő b 0. 4 8 ŐƏĺ ƒ ƕķ Əĺѵ Ɛ ő b Əĺ Ѷ Ɣ  ŐƏĺѵ Ə ķƐĺ ƑƑ ő b .38 b 0. 78 _ŐƏĺƔ ѵ ķƐ ĺƐ Ə ő b .16 $ c 63.68 ŐƔ Ɛ ĺƑƐ ķƕ Ɩ ĺƐ Ѷ ő 77 .9 9 Őѵ Ə ĺƐƏ ķƐƏ Ɛ ĺƑ Ƒ ő 0. 82 ŐƏ ĺƔ Ѷ ķƐ ĺƐ ƒ ő .2 3 Əĺ Ѷ Ɣ  ŐƏĺѵ Ƒ ķƐĺ Ɛ ƕ ő .3 1 16.6 7 ŐƐ Ɠ ĺƑ ѵ ķƐ Ɩ ĺƓ ƕ ő 18 .1 9 ŐƐ Ɣ ĺƒƕ ķƑƐ ĺƔ Ɠ ő 0. 92 ŐƏ ĺƕƒ ķƐ ĺƐ Ɣ ő ĺƓ Ɣ 0. 98 ŐƏ ĺѶ Ə ķƐ ĺƑ Ɛő .8 7   c 52 .4 1 (4 2 .42 , 6 4.7 6) 79 .2 8 (6 0. 59 , 1 0 3 .73 ) 0.66 (0.4 7, 0. 92 ) .0 2 0. 71 (0. 51 , 0. 98 ) .0 4 16 .96 (1 4. 50, 1 9. 8 3) 21 .1 7 (1 8 .2 8 , 2 4. 52 ) 0. 8 0 (0.6 5, 0. 99 ) .0 4 Əĺ Ѷ Ɣ  ŐƏ ĺѵ Ɩ ķƐ ĺƏ Ɠő .1 1 !  c ƔƓ ĺƏ Ə  ŐƓƑ ĺƑ ѵ ķѵ Ɩ ĺƏ Ə ő 6 8 .6 6 ŐƓƖ ĺƒ ѵ ķƖ Ɣ ĺƔ Ə ő 0. 79 ŐƏ ĺƔ ƒ ķƐ ĺƐ ƕ ő .2 4 0. 8 0 ŐƏĺ Ɣ ƒ ķƐĺ Ƒ Ɛ ő .2 9 10 .1 3 (8 .3 9, 12 .2 4) 14 .2 4 (1 1 .7 3 , 17 .2 8) 0. 71 (0. 5 4, 0. 93 ) .0 2 0.73 (0. 57 , 0. 95 ) .0 2 b0 d 0. 4 0 ŐƏ ĺƑ Ɣ ķƏ ĺѵ Ɠő 0.68 ŐƏĺ Ɠ Ɠ ķƐĺƏ ѵ ő Əĺ Ɣ Ѷ  ŐƏ ĺƒ Ə ķƐ ĺƐ Ɛő .1 0 0. 66 _ŐƏĺƒ Ɣ ķƐĺ Ƒ ѵ ő .2 1 Ɛĺ Ɣ  ŐƏ ĺѶ Ə ķƑ ĺƔ Ɛő b 0. 82 ŐƏ ĺƔ Ɛ ķƐ ĺƒ ƒ ő b 1. 82 ŐƏĺ ƖƏķ ƒ ĺƕ Əő b .09 b Ɛĺ Ɣ Ɛ  ŐƏ ĺѶ Ѷ ķƑ ĺѵ Ɛő b .1 4 b oѴbo  |‹ r ;Ɛ c ƒƒĺ ƕ Ɣ  ŐƑ Ɠ ĺƒ Ɠ ķƓ ѵ ĺѶ Ɛ ő ƒƔ ĺƔ Ɩ ŐƑ ѵ ĺƔ Ə ķƓ ƕĺ Ѷ Ə ő Əĺ Ɩ Ɣ  ŐƏ ĺѵ Ɛ ķƐ ĺƓ ƕ ő .8 1 1. 0 4 ŐƏĺѵѵ ķƐ ĺѵ Ɣ ő .8 6 11 .0 7 ŐƖ ĺƑ Ѷ ķƐ ƒ ĺƐ Ɩ ő 11 .3 2 ŐƖ ĺƓ Ɛ ķƐ ƒ ĺѵ Ɛ ő 0. 98 ŐƏĺ ƕ ѵ ķƐĺ Ƒ ѵ ő .8 6 1. 0 3 ŐƏ ĺѶ Ə ķƐ ĺƒ Ƒő .8 2 oѴbo  |‹ r ;Ƒ c ѵƔ ĺƒ ѵ ŐƓƖ ĺƓ Ɣ ķѶ ѵ ĺƓ Ə ő 6 0. 4 3 ŐƓ Ƒ ĺƐ Ɠ ķѶ ѵ ĺѵ ѵ ő 1.0 8 ŐƏ ĺѵ Ɩ ķƐ ĺѵ Ɩ ő .73 1. 14 ŐƏ ĺƕƒ ķƐ ĺƕѶ ő ĺƔ ƕ 22 .73 ŐƐ Ѷ ĺƕ Ɠ ķƑƕ ĺƔƕ ő 20 .4 6 ŐƐ ѵ ĺƔ Ɠ ķƑ Ɣ ĺƒ Ɛ ő 1. 11 ŐƏ ĺѶ ƒ ķƐ ĺƓ Ѷ ő .4 7 1. 18 _ŐƏĺѶ Ɩ ķƐ ĺƔ ѵ ő ĺƑ Ɣ oѴbo  |‹ r ;ƒ c 23 .4 3 ŐƐƕ ĺƏ ƒ ķƒ Ƒ ĺƑƓ ő 19 .4 1 ŐƐ ƒ ĺѵ Ɩ ķƑ ƕĺ Ɣ Ƒ ő 1. 21 ŐƏĺ ƕ ѵ ķƐĺ Ɩ Ƒ ő .4 2 1. 24 _ŐƏĺƕ ѵ ķƑ ĺƏ Ɛő .38 10 .1 7 ŐѶ ĺƑ Ɩ ķƐ Ƒ ĺƓ Ѷ ő 7. 71 Őѵ ĺƑ Ɣ ķƖ ķƔ ƒ ő 1. 32 ŐƏ ĺƖ Ѷ ķƐ ĺƕ ƕ ő .06 1.3 9 (1 .0 4, 1 .8 4) .03  mƐ d 3. 97 ŐƑ ĺѶ ѵ ķƔ ĺƔ Ə ő 4. 87 Őƒ ĺƕƏ ķѵ ĺƓ Ə ő 0. 82 ŐƏĺ Ɣ ƒ ķƐĺ ƑƔ ő .3 4 0. 89 _ŐƏĺƔ Ɩ ķƐ ĺƒ Ƒő ĺƔ Ɣ 1. 18 ŐƐ ĺƏ ƒ ķƐ ĺƒ Ɣ ő Ɛĺ Ɛ Ɣ  ŐƐ ĺƏ Ə ķƐ ĺƒ ƒ ő 1.03 ŐƏ ĺѶ Ɣ ķƐ ĺƑ Ɣ ő .78 1. 0 6 ŐƏ ĺѶ ƕķƐ ĺƑ Ѷ ő ĺƔ Ѷ  mƒ d 1. 37 ŐƐ ĺƐ Ɣ ķƐ ĺѵ Ɠő Ɛĺ Ɣ Ƒ  ŐƐ ĺƑ Ɛ ķƐ ĺƖ Ə ő 0. 90 ŐƏ ĺѵ Ѷ ķƐ ĺƑ Ə ő .4 8 0. 91 _ŐƏĺѵ Ѷ ķƐ ĺƑ Ɛő ĺƔ Ɛ Ə ĺƔ ƕ  ŐƏĺ ƔƏķ Əĺѵ Ɣ ő Əĺ ƔƏ  ŐƏĺ Ɠ Ɠ ķƏĺ Ɣ ƕ ő 1. 14 ŐƏ ĺƖ Ɣ ķƐ ĺƒ ƕ ő ĺƐ Ɣ 1. 17 ŐƏ ĺƖ Ѷ ķƐ ĺƒ Ɩ ő .09  mƓ d Əĺ Ɣ ƒ  ŐƏĺ Ɠ Ɛ ķƏĺѵ Ɩ ő Əĺ ƔƏ  ŐƏ ĺƓ Ə ķƏ ĺѵ ƒ ő 1.0 6 ŐƏ ĺƕ Ɣ ķƐ ĺƔ Ɛő .73 1. 0 9 ŐƏ ĺƕ ƕķƐ ĺƔ Ɠő .6 1 0. 22 _ŐƏĺƑ Ə ķƏ ĺƑ Ɣ ő 0. 21 ŐƏĺ Ɛ Ɩ ķƏĺ Ƒ ƒ ő ƐĺƏƔ  ŐƏ ĺƖ Ə ķƐ ĺƑ Ƒő ĺƔ Ƒ 1.0 7 ŐƏ ĺƖ Ƒ ķƐ ĺƑ Ɠő .3 9  mƔ d 2. 91 ŐƑ ĺƐ ƕķƒ ĺѶ Ɩ ő 3. 46 ŐƑ ĺƕ Ɛ ķƓ ĺƓ ƒ ő 0. 8 4 ŐƏ ĺƔ ƕķƐ ĺƑ ƒ ő .3 6 0. 92 _ŐƏĺѵ ƒ ķƐ ĺƒ ƒ ő ĺѵ Ɣ 0. 96 ŐƏ ĺѶ ƒ ķƐ ĺƐ Ƒő 0. 8 8 ŐƏĺ ƕ ѵ ķƐĺƏƑ ő 1.0 9 ŐƏ ĺѶ Ɩ ķƐ ĺƒ Ɠő .4 1 1. 14 ŐƏ ĺƖ ƒ ķƐ ĺƒ Ɩ ő .2 2  mѵ  d 4. 82 Őƒ ĺѵ ѵ ķѵ ĺƒ Ɠő 4. 81 Őƒ ĺѶ Ɛ ķѵ ĺƏ Ѷ ő 1.0 0 ŐƏĺ ƕ Ə ķƐĺ Ɠ Ɠ ő 1.0 0 1.0 1 ŐƏ ĺƕƑ ķƐ ĺƓ Ƒő .9 7 1. 0 8 ŐƏ ĺƖ ƒ ķƐ ĺƑ Ɣ ő 0. 93 ŐƏĺ ƕ Ѷ ķƐĺ Ɛ Ə ő 1. 16 ŐƏ ĺƖ ƒ ķƐ ĺƓ Ɣ ő .1 9 1. 24 (1 .0 1 , 1 .5 3) .0 4  mѵ  d 1. 6 4 ŐƐ ĺƏ Ɠ ķƑ ĺƔ Ɩ ő 2. 27 ŐƐ ĺƓ ѵ ķƒ ĺƔ Ɠ ő 0. 72 _ŐƏĺƒѶķ Ɛ ĺƒ ѵ ő .3 1 0.72 ŐƏ ĺƒѶķ Ɛ ĺƒ Ɠ ő .2 9 Əĺ Ɣ ѵ  ŐƏ ĺƓ ƕķƏ ĺѵ Ѷ ő 0. 47 ŐƏĺ ƒ Ɩ ķƏĺ Ɣ ƕ ő 1. 20 ŐƏ ĺƖ ƒ ķƐ ĺƔ ѵ ő .17 Ɛĺ ƑƔ  ŐƏ ĺƖ ƕķƐ ĺѵ Ɛő .0 8  mƕ d Ɣ ĺƕƑ ŐƓĺƔ Ɛ ķƕ ĺƑ ƕ ő 6.6 2 ŐƔ ĺƒ Ɛ ķѶ ĺƑ ѵő 0. 86 ŐƏ ĺѵ ƒ ķƐ ĺƑ Ə ő .38 Əĺ Ѷ Ɣ  ŐƏ ĺѵ Ƒ ķƐ ĺƐ Ɣ ő .2 9 1. 93 _ŐƐĺƕƏ ķƑ ĺƐ Ѷ ő 1. 8 3 ŐƐ ĺѵ Ɛ ķƑ ĺƏ ƕ ő 1.0 6 ŐƏ ĺѶ Ɩ ķƐ ĺƑ ѵ ő ĺƔ Ɣ 1.0 9 ŐƏ ĺƖ ƒ ķƐ ĺƒ Ə ő .2 9  mƖ ( d 2. 4 0 ŐƐ ĺѶ ƒ ķƒ ĺƐ ѵ ő Ƒĺ Ɣ Ƒ  ŐƑ ĺƏ Ɛ ķƒ ĺƐ ѵ ő Əĺ Ɩ Ɣ  ŐƏ ĺѵ ƕķƐ ĺƒ ѵ ő .79 0. 99 ŐƏĺ ƕ Ɛ ķƐĺ ƒ ƕ ő .9 4 0. 6 3 ŐƏ ĺƔ Ɣ ķƏ ĺƕƑő Əĺ Ɣ ƕ  ŐƏĺ Ɠ Ɩ ķƏĺѵ Ɣ ő 1. 12 ŐƏĺ Ɩ Ƒ ķƐĺ ƒѵ ő .2 6 1. 16 _ŐƏĺƖ ѵ ķƐ ĺƓ Ə ő .1 2  mƐ Ɠ d ƑĺƔƓ  ŐƐ ĺѶ Ƒ ķƒ ĺƔ ѵ ő 2.8 1 ŐƐ ĺѶ ѵ ķƓ ĺƑ ѵ ő 0. 90 ŐƏ ĺƔƓ ķƐ ĺƔ ƒ ő .70 0. 8 8 ŐƏ ĺƔ Ƒ ķƐ ĺƔ Ɛ ő ĺѵ Ɣ 1.0 9 ŐƏ ĺƖ ƒ ķƐ ĺƑ Ɩ ő 1.0 0 ŐƏ ĺѶ Ɣ ķƐ ĺƐ Ѷ ő 1.0 9 ŐƏĺ Ѷ ƕķ Ɛĺ ƒ ƕ ő .4 6 1. 13 _ŐƏĺƖ Ə ķƐ ĺƓ ƒ ő .2 8 $    ƑՊ Ő o m |b m † ; 7 ő Ő o m |b m † ; vő

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(b ) Va cc in e an tig en A nt ib od ie s t o p ri m ar y c ou rs e of v ac ci ne s e nd in g a t 6 m o of a ge m ea su re d a t 7 m o of a ge A nt ib od ie s t o p ri m ar y c ou rs e of v ac ci ne s e nd in g a t 6 m o of a ge m ea su re d a t 13 m o of a ge Fe m al e (n = 4 8) M al e (n = 4 3) &m-7f†v |; 7  GM R (9 5% C I) $ ‰ oŊ vb7;7  P-value 7f†v |; 7 e GM R (9 5% C I) $ ‰ oŊ vb7;7  P-value Fe m al e (n = 1 58 ) Male (n = 1 49 ) &m-7f†v |; 7  GM R (9 5% C I) $ ‰ oŊ vb7;7  P-value 7f†v |; 7 f GM R (9 5% C I) $ ‰ oŊ vb7;7  P-value G M C (9 5% C I) G M C (9 5% C I) G M C (9 5% C I) G M C (9 5% C I)  mƐ Ѷ  d 2.68 ŐƐ ĺƖ ѵ ķƒ ĺѵ Ɣ ő 3. 27 ŐƑ ĺƔ Ɩ ķƓ ĺƐ ƒ ő 0. 82 ŐƏ ĺƔ Ɣ ķƐ ĺƑ Ɛő .3 1 0. 8 3 ŐƏĺ Ɣ ѵ ķƐĺ ƑƑ ő ĺƒ Ɣ 0.6 9 ŐƏ ĺѵ Ə ķƏ ĺƕѶ ő 0.6 2 ŐƏ ĺƔ Ɠ ķƏ ĺƕ Ɛő 1. 11 ŐƏĺ Ɩ Ƒ ķƐĺ ƒ Ɠ ő .2 8 1. 16 ŐƏ ĺƖ ƕķƐ ĺƓ Ə ő .10  mƐ Ɩ  d 1. 7 7 ŐƐ ĺƒ Ɠ ķƑ ĺƒ Ɠ ő 1. 67 ŐƐ ĺƑ Ɣ ķƑ ĺƑ Ƒ ő 1.0 6 ŐƏ ĺƕ Ɛ ķƐ ĺƔ Ѷ ő .7 7 1. 14 _ŐƏĺƕѵ ķƐĺѵ Ɩ ő ĺƔ Ƒ 0. 4 8 ŐƏ ĺƒ Ѷ ķƏ ĺѵ Ə ő Əĺ Ɠ Ɣ  ŐƏĺ ƒ ƕķ Əĺ Ɣ Ɠ ő 1.0 6 ŐƏĺ ƕ Ɩ ķƐĺ Ɠ Ƒ ő .70 1. 10 ŐƏ ĺѶ ƒ ķƐ ĺƓ ƕ ő ĺƔ Ɛ  mƐ Ɩ d 10 .2 0 Őƕ ĺƕ Ɛ ķƐ ƒ ĺƔ Ə ő 13 .2 2 ŐƐ Ə ĺƓ Ə ķƐ ѵ ĺƕ Ɩ ő 0. 77 ŐƏĺ Ɣ ƒ ķƐĺ Ɛ Ɛ ő .1 7 0. 8 0 ŐƏĺ Ɣ ѵ ķƐĺ Ɛ Ɣ ő .2 2 3 .2 1 ŐƑ ĺƕƑ ķƒ ĺƕ Ɩ ő 3.0 0 ŐƑ ĺƔ Ƒ ķƒ ĺƔ Ѷ ő 1.0 7 ŐƏĺ Ѷ Ɠ ķƐĺ ƒѵ ő ĺƔ Ѷ 1. 11 ŐƏ ĺѶ ƕķƐ ĺƓ Ə ő .4 0  mƑƒ d 2. 27 ŐƐ ĺѵ Ɠ ķƒ ĺƐ Ɣ ő 2. 41 ŐƐ ĺѵ Ɩ ķƒ ĺƓ Ɠő 0. 94 ŐƏ ĺƔ Ѷķ Ɛ ĺƔ Ƒ ő .8 1 0. 96 _ŐƏĺѵ Ə ķƐ ĺƔ Ƒő ĺѶ Ɣ 0.63 ŐƏĺ Ɣ Ƒ ķƏĺ ƕƕ ő Əĺ ƔƏ  ŐƏĺ Ɠ Ɛ ķƏĺѵ Ɛ ő 1. 26 ŐƏ ĺƖ ѵ ķƐ ĺѵ ѵ ő .1 0 1. 27 _ŐƏĺƖƕķƐ ĺѵ Ѷ ő .0 8 V ac ci ne an tig en A nt ib od ie s t o 1 2-m o v ac ci ne s m ea su re d 13 m o of a ge Fe male (n = 73 ) Male (n = 7 1) &m-7f†v |; 7 GM R (9 5% C I) $ ‰ oŊ vb7;7  P-value 7f†v |; 7 e GM R (9 5% C I) $ ‰ oŊ vb7;7 P-value G M C (9 5% C I) G M C (9 5% C I) ;-vѴ;v c 3.66 (3 .0 5 -4 .4 0) 2. 49 (1 .8 3-3. 41 ) 1. 47 (1 .0 3 , 2 .1 0) .0 3 1 .4 5 (1 .0 1 , 2 .0 9) .0 4 †lrv c ƔѶ ĺƖ ƒ  ŐƓ ƒ ĺƒ Ɛ ķѶ Ə ĺƑ Ə ő Ɣƕ ĺƓ Ə ŐƓ Ƒ ĺƏ ƕķƕѶ ĺƒ Ƒő 1.03 ŐƏĺѵ ƕķ Ɛĺ Ɣ Ѷ ő .9 0 0.9 4 ŐƏ ĺѵ Ɣ ķƐ ĺƒ Ɣ ő .73 Ru be lla c 6 0.78 ŐƓƓ ĺѶ ƒ ķѶ Ƒ ĺƓ Ə ő ƓƔ ĺƏ Ɠ  Őƒ Ɛ ĺƕ Ɠ ķѵ ƒ ĺƖ Ƒ ő Ɛĺ ƒ Ɣ  ŐƏ ĺѶ Ɣ ķƑ ĺƐ Ɠő .2 0 Ɛĺ ƑƔ  ŐƏ ĺѶ ѵķ Ɛ ĺѶ Ɛ ő ĺƑ Ɣ ;m d 1 9. 47 ŐƐ ѵ ĺƓƕ ķƑ ƒ ĺƏ Ə ő ƐƔ ĺѶ Ɩ  ŐƐ Ƒ ĺѶ Ɠ ķƐ Ɩ ĺѵ ѵ ő 1. 23 ŐƏĺ Ɩ Ɠ ķƐĺѵ Ə ő .1 4 1. 27 _ŐƏĺƖƕķƐ ĺѵ Ɣ ő .0 8 b0 d 1 8 .2 1 ŐƐ ƒ ĺƏ Ѷ ķƑ Ɣ ĺƒƔ ő 13 .0 1 ŐѶ ĺƕ Ɠ ķƐ Ɩ ĺƒ Ѷ ő 1. 4 0 ŐƏ ĺѶ Ɠ ķƑ ĺƒ ƒ ő .2 0 Ɛĺ Ɣƒ  ŐƏ ĺƖ ƒ ķƑ ĺƔ ƒ ő .10 $; |-m † v c 0 .8 3 ŐƏ ĺѵ Ɠ ķƐ ĺƏ Ѷ ő 1. 19 ŐƏĺ Ѷ Ѷ ķƐĺѵ Ə ő 0. 70 ŐƏ ĺƓ ƕķƐ ĺƏ Ɠő .0 7 0. 73 ŐƏ ĺƓ Ɩ ķƐ ĺƏ Ѷ ő .1 2  o Ѵ77 ; m o |; vu ; v† Ѵ| v‰ b| _ PŊˆ -Ѵ† ;ƺĺ Ə Ɣ ĺ  0 0 u; ˆ b-|b o m vĹ  ķ -1b ѴѴ; -Ѵl ; || ; Ŋ † ࣐ ub m ĸ ķ1 o m =b 7 ; m 1;b m |; uˆ -Ѵĸ   ķ= bѴ-l ; m |o † v_ -; l -] ] Ѵ† |b m bmĸ   ķ] ; o l ; |u b1l ; - m-m |b 0 o 7 ‹1 o m 1; m |u -| bo mĸ  ! ķ] ; o l ; |u b1l ; - m-m |b 0 o 7 ‹u -| boĸ b0 ķ Haemophilus in fluenz ae | ‹ r ;0ĸ ; m  ķl ; m bm ] o 1o 11 † v ĸ  ! ķl ; -v Ѵ; vŊ l † l r vŊ u† 0 ; ѴѴ-ĸ m ķr m ; † l o 1o 11 † vv ; uo |‹ r ; ĸ !  ķr ; u| -1 |b mĸ $ ķr ; u| † vv bv | oŠ bm ĺ aƏĺƏ Ɛ & ņl -|Ɛ ƒl oo=-] ; ĺ bm 1Ѵ † 7 ; vo m Ѵ‹r -u| b1 br -m |v‰ _ o_ -ˆ;m o |_ -7 b0 Ŋ ; m  ĺ c& ņl  ĺ d੿] ņl  ĺ e 7 f† v| ; 7= o ul -| ; um -Ѵ7 $ r -Ő 7 br _ |_ ; ub -Ŋ |; |-m † vŊ-1; † ѴѴ† -ur ; u| † vv bv ő-m 7| ub ˆ -Ѵ; m |b m =Ѵ † ; m Œ-ˆ -11 bm ;7 † ub m ]r u; ] m -m 1‹ ķ] ; v| -| bo m - Ѵ-] ; ķ ˆ -11 bm -| bo mv |-|† vķ-] ;-|= bu v| $  -Ŋ  ; r  Ŋ  ( Ŋ b0 ņ  ( Ɛ ƒ  ˆ -11 bm -| bo m ķ-] ;-|v -l r Ѵbm ]-m 7| bl ;0 ; |‰ ; ; mˆ -11 bm -| bo m-m 7v -l r Ѵbm ]† vb m ]l † Ѵ| br Ѵ;Ѵ bm ; -uu ; ] u; vv bo m ĺ = 7 f† v| ; 7= o ul -| ; um -Ѵ7 $ r -Ő 7 br _ |_ ; ub -Ŋ |; |-m † vŊ-1; † ѴѴ† -ur ; u| † vv bv ő-m 7| ub ˆ -Ѵ; m |b m =Ѵ † ; m Œ-ˆ -11 bm ;7 † ub m ]r u; ] m -m 1‹ ķ] ; v| -| bo m - Ѵ-] ; ķ -m 7  !ˆ -11 bm -| bo mv |-|† vķ-] ;-|= bu v| $  -Ŋ  ; r Ŋ ( Ŋb0 ņ   ( Ɛ ƒˆ -11 bm -| bo m ķ-] ;-|v -l r Ѵbm ]-m 7| bl ;0 ; |‰ ; ; mˆ -11 bm -| bo m -m 7v -l r Ѵbm ]† vb m ]l † Ѵ| br Ѵ;Ѵ bm ; -uu ; ] u; vv bo m ĺ $    ƑՊ Ő o m |b m † ; 7 ő

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Petra Zimmermann _||rvĹņņou1b7ĺou]ņƏƏƏƏŊƏƏƏƑŊƑƒѶѶŊƓƒƐѶ

R E FE R E N C E S

 Ɛĺ !b|Œ ķ †b ķ -ѴѴo1_ ķ †u|bv ĺ omŊvr;1b=b1 ;==;1| o= -1bѴѴ; -Ѵl;||;Ŋ†;ubm ˆ-11bm; om |_; bll†m; u;vromv; |o uo†|bm; blŊ l†mbv-|bomvĺVaccineĺƑƏƐƒĸƒƐĹƒƏƖѶŊƒƐƏƒĺ

 Ƒĺ ,bll;ul-mm ķ †u|bv ĺ -1|ouv |_-| bm=Ѵ†;m1; |_; bll†m; u;Ŋ vromv;|oˆ-11bm-|bomĺClin Microbiol RevĺƑƏƐƖĸƒƑŐƑőĹrbbĹ;ƏƏƏѶƓŊƐѶĺ  ƒĺ -mķ"_-o*ķ,_;m]ķ;|-Ѵĺ!;ˆ-11bm-|bomo=momŊ-m7Ѵo‰Ŋu;Ŋ vrom7;uv-=|;u-v|-m7-u7|_u;;7ov;_;r-|b|bvˆ-11bm;v1_;7†Ѵ;ĺ

Hum Vaccin ImmunotherĺƑƏƐƑĸѶĹƐѶƓƔŊƐѶƓƖĺ

 Ɠĺ l;m-1- ķ-u1b-Ŋ"b1bѴb-ķ-u1b-Ŋou0;bu-ķo1;|-!ķ$ouu;v(ĺ m|broѴ‹ub0ov‹Ѵub0b|oѴr_ovr_-|;u;vromv;o=ru;l-|†u;bm=-m|v|o rubl-u‹ -m7 0oov|;u ˆ-11bm-|bom ‰b|_ - 1ol0bm;7 7br_|_;ub-Ŋ|;|Ŋ -m†vŊ-1;ѴѴ†Ѵ-u r;u|†vvbvŊ_;r-|b|bv Ŋbm-1|bˆ-|;7 roѴbo

ˆbu†vņHae-mophilus influenzae|‹r;0ˆ-11bm;ĺPediatricsĺƑƏƏƕĸƐƐƖĹ;ƐƕƖŊ;ƐѶƔĺ

 Ɣĺ -uubv(ķ--h)ķ-m7Ѵ;‹"ķ;|-Ѵĺ==;1|o=-m|b0bo|b1Ŋl;7bŊ -|;7 lb1uo0bol; lo7†Ѵ-|bom om uo|-ˆbu†v ˆ-11bm; bll†mo];mb1Ŋ b|‹Ĺ - _†l-mķ u-m7olbŒ;7Ŋ1om|uoѴ ruoo=Ŋo=Ŋ1om1;r| |ub-Ѵĺ Cell Host

MicrobeĺƑƏƐѶĸƑƓŐƑőĹƐƖƕŊƑƏƕĺ;Ɠĺ

 ѵĺ Ѵo|hbm "ĺ ouu;Ѵ-|;v o= ruo|;1|bom bm7†1;7 0‹ ˆ-11bm-|bomĺ Clin

Vaccine ImmunolĺƑƏƐƏĸƐƕĹƐƏƔƔŊƐƏѵƔĺ  ƕĺ u;b7Ѵ"ķ$ov|l-mmķ†uˆ;uvķ;|-Ѵĺll†mb|‹-]-bmv|l;-vѴ;vķ l†lrvķu†0;ѴѴ-ķˆ-ub1;ѴѴ-ķ7br_|_;ub-ķ|;|-m†vķroѴboķ_;r-|b|bv-m7 _;r-|b|bv-lom]-7†Ѵ|-v‹Ѵ†lv;;h;uvbm|_;;|_;uѴ-m7vķƑƏƐѵĺ VaccineĺƑƏƐѶĸƒѵĹƐѵѵƓŊƐѵƕƑĺ  Ѷĺ "1_;rr!ķ;u0;uvķ ;uu;bu-ķ!;bl;ubmhķˆ-m7;uѴbv !ĺ moˆ;Ѵl†Ѵ|brѴ;ŠroѴboˆbu†v0bm7bm]bm_b0b|bom-vv-‹-rrѴb1-0Ѵ;=ou Ѵ-u];v;uov†uˆ;bѴѴ-m1;-m7ˆ-11bm;v|†7b;vķ‰b|_o†||_;†v;o=Ѵbˆ; roѴboˆbu†vĺJ Virol MethodsĺƑƏƐƕĸƑƓƐĹƐƔŊƑƒĺ

 Ɩĺ "|-uh ķ "1_om=;Ѵ7 ķ -u] ķ oѴŒ ķ (oum‰-Ѵ7 ķ b;mŒѴ; &ĺ ";uoru;ˆ-Ѵ;m1; -m7 7;|;ulbm-m|v o= 7br_|_;ub-ķ |;|-m†v -m7

roѴbol‹;Ѵb|bv-m|b0o7b;v-lom]-7†Ѵ|vbm;uѴbmķ;ul-m‹ĺVaccine. ƐƖƖƖĸƐƕĹѶƓƓŊѶƔƏĺ

ƐƏĺ -bmŒ &ķ ;m;‰;bm ķ v1_ ķ =;b==;u ķ ;u];u ķ u†0;1hŊ o;0;mv|;bmĺmv†==b1b;m|ruo|;1|bom=ou_;-Ѵ|_‹;Ѵ7;uѴ‹-7†Ѵ|v0‹ |;|-m†v-m7$ˆ-11bm;vĺVaccineĺƑƏƏƔĸƑƒĹƒƑƒƑŊƒƑƒƔĺ

ƐƐĺ ;u];m ķ 1 †bѴѴ-m ķ b;Ѵ‹ ķ ŒŒ-|bŊ!b1; $ķ "†||;u !)ķ (bu;ѴѴ-ĺror†Ѵ-|bomŊ0-v;7v;uoѴo]b1v†uˆ;‹o=bll†mb|‹|o|;|-Ŋ m†vbm|_;&mb|;7"|-|;vĺN Engl J MedĺƐƖƖƔĸƒƒƑĹƕѵƐŊƕѵѵĺ ƐƑĺ Ѵ;bm "ķ Ѵ-m-]-m ĺ ";Š 7b==;u;m1;v bm bll†m; u;vromv;vĺ Nat

Rev ImmunolĺƑƏƐѵĸƐѵĹѵƑѵŊѵƒѶĺ

Ɛƒĺ bv_ĺ$_;*Ŋ=bѴ;vbmbll†mb|‹Ĺv;ŠŊ0-v;77b==;u;m1;vru;7bvrov; bll†m;u;vromv;vĺNat Rev ImmunolĺƑƏƏѶĸѶĹƕƒƕŊƕƓƓĺ

ƐƓĺ ,bll;ul-mm ķ †u|bv ĺ $_; bm=Ѵ†;m1; o= |_; bm|;v|bm-Ѵ lb1uo0bŊ ol;omˆ-11bm;u;vromv;vĺVaccineĺƑƏƐѶĸƒѵĹƓƓƒƒŊƓƓƒƖĺ

ƐƔĺ -u1b-Ŋol;Œ ķ omŒ-Ѵ;ŒŊ;7u-fo ķ -l-1_oŊuuo‹o ĺ !oѴ; o= v;Šv|;uob7_oulom;vbm0-1|;ub-ѴŊ_ov|bm|;u-1|bomvĺBiomed Res Int. 2013;2013:928290.

Ɛѵĺ u-mv;m ķ ˆ-m ;;h ķ ou]_†bv $ķ ;| -Ѵĺ $_; blr-1| o= ]†| lbŊ 1uo0bo|-om];m7;uŊvr;1b=b17b==;u;m1;vbmbll†mb|‹ĺFront Immunol. ƑƏƐƕĸѶĹƕƔƓĺ

Ɛƕĺ (;l†ub !ķ "‹Ѵˆb- ķ Ѵ;bm "ķ ;| -Ѵĺ $_; lb1uo];m7;uol; u;Ŋ ˆ;-Ѵ;7Ĺ v;Š 7b==;u;m1;v bm 0b7bu;1|bom-Ѵ bm|;u-1|bomv 0;|‰;;m |_; lb1uo0bo|-ķ _oulom;vķ bll†mb|‹ -m7 7bv;-v; v†v1;r|b0bѴb|‹ĺ Semin

ImmunopatholĺƑƏƐƖĸƓƐŐƑőĹƑѵƔŊƑƕƔĺ

ƐѶĺ ,bll;ul-mmķ†u|bvĺ -1|ouvbm=Ѵ†;m1bm]|_;bm|;v|bm-Ѵlb1uo0bŊ ol;7†ubm]|_;=buv|‹;-uo=Ѵb=;ĺPediatr Infect Dis JĺƑƏƐѶĸƒƕŐƐƑőĹ;ƒ ƐƔŊ;ƒƒƔĺ

ƐƖĺ (o‹v;‹ķ;ѴѴ‹ ķ -mv_-‰;$!ķ;|-Ѵĺ$_;bm=Ѵ†;m1;o=l-|;um-ѴѴ‹ 7;ubˆ;7 -m|b0o7‹ -m7 bm=-m| -]; -| ˆ-11bm-|bom om bm=-m| ˆ-11bm; u;vromv;vĹ -m bm7bˆb7†-Ѵ r-u|b1br-m| l;|-Ŋ-m-Ѵ‹vbvĺ JAMA Pediatr. ƑƏƐƕĸƐƕƐĹѵƒƕŊѵƓѵĺ ƑƏĺ b1h;ubm]ķu-mo== ķub1hvom!ķ;|-Ѵĺo7†Ѵ-|bomo=|_;blŊ l†m;v‹v|;l0‹_†l-mlbѴh-m7bm=-m|=oul†Ѵ-1om|-bmbm]m†1Ѵ;oŊ |b7;vĺPediatricsĺƐƖƖѶĸƐƏƐĹƑƓƑŊƑƓƖĺ ƑƐĺ -0v| ķ"r-7‹ )ĺ==;1|o=0u;-v|Ŋ=;;7bm]om-m|b0o7‹u;vromv; |o1omf†]-|;ˆ-11bm;ĺLancetĺƐƖƖƏĸƒƒѵĹƑѵƖŊƑƕƏĺ

ƑƑĺ "bѴ=ˆ;u7-Ѵ "ķ o7bm ķ &Ѵ-moˆ- ķ -_mŊ,oub1 ķ -mvom ķ Ѵ1;mĺom]|;ul;m_-m1;l;m|o=|_;]Ƒ-m|b0o7‹u;vromv;|o

Haemophilus influenzae|‹r;00‹0u;-v|Ŋ=;;7bm]ĺPediatr Infect Dis J.

ƑƏƏƑĸƑƐĹѶƐѵŊѶƑƐĺ

Ƒƒĺ -_mŊ,oub1ķ †Ѵ1ombv ķbmoѴbķ;|-Ѵĺm|b0o7‹u;vromv;v|or-uŊ ;m|;u-Ѵ-m7ou-Ѵˆ-11bm;v-u;blr-bu;70‹1omˆ;m|bom-Ѵ-m7Ѵo‰ruoŊ |;bm =oul†Ѵ-v -v 1olr-u;7 |o 0u;-v|Ŋ=;;7bm]ĺ Acta Paediatr Scand. ƐƖƖƏĸƕƖĹƐƐƒƕŊƐƐƓƑĺ

ƑƓĺ b1_b1_;uoĺ==;1|o=0u;-v|Ŋ=;;7bm]omou-Ѵu_;v†vuo|-ˆbu†vˆ-1Ŋ 1bm;v;uo1omˆ;uvbomĹ-l;|--m-Ѵ‹vbvĺJ Infect DisĺƐƖƖƏĸƐѵƑĹƕƔƒŊƕƔƔĺ ƑƔĺ _bѴ;m]b!ķ"bl†‹-m7bķ;-1_ķ;|-Ѵĺvvo1b-|bomo=l-|;um-ѴblŊ l†mb|‹‰b|_uo|-ˆbu†vˆ-11bm;bll†mo];mb1b|‹bmŒ-l0b-mbm=-m|vĺ

PLoS OneĺƑƏƐѵĸƐƐĹ;ƏƐƔƏƐƏƏĺ

Ƒѵĺ Ѵ-vv!ķm] ķ"|oѴѴķm]!$ĺll†m;u;vromv;|ouo|-ˆbu†vˆ-1Ŋ 1bm;v -lom] 0u;-v|Ŋ=;7 -m7 mom0u;-v|Ŋ=;7 1_bѴ7u;mĺ Adv Exp Med

BiolĺƐƖƖƐĸƒƐƏĹƑƓƖŊƑƔƓĺ

Ƒƕĺ oom""ķ)-m]+ķ"_-m;ķ;|-Ѵĺm_b0b|ou‹;==;1|o=0u;-v|lbѴh om bm=;1|bˆb|‹ o= Ѵbˆ; ou-Ѵ uo|-ˆbu†v ˆ-11bm;vĺ Pediatr Infect Dis J. ƑƏƐƏĸƑƖĹƖƐƖŊƖƑƒĺ