Immunogenicity and Safety of Pandemic Influenza

Physiol Biochem 2016;40:921-932 Cellular Physiology Cell © 2016 The Author(s). Published by S. Karger AG, Basel DOI: 10.1159/000453150 DOI: 10.1159/000453150 © 2016 The Author(s) online:December 07, 2016 www.karger.com/cpb Published online: Published by S. Karger AG, Basel and Biochemistry Published www.karger.com/cpb December 07, 2016

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Guo et al.: (YDOXDWLRQRI+19DFFLQH6DIHW\DQG(IÀFDF\ Accepted: October 25, 2016

This article is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND) (http://www.karger.com/Services/OpenAccessLicense). Usage and distribution IRUFRPPHUFLDOSXUSRVHVDVZHOODVDQ\GLVWULEXWLRQRIPRGLÀHGPDWHULDOUHTXLUHVZULWWHQSHUPLVVLRQ

Original Paper

Immunogenicity and Safety of Pandemic ,QÁXHQ]D+19DFFLQHVLQ+HDOWK\$GXOWV WKURXJK0HWD$QDO\VLV Qi Guoa Ze Liua Jingxia Gaoa Jian Zhoua Guoyang Liaoa

Wenzhu Hua Yina Cuna

Weidong Lib

The Fifth Department of Biological Products, Institute of Medical Biology, Chinese Academy of Medical Science and Peking Union Medical College, Kunming, bThe Department of Production Administration , Institute of Medical Biology, Chinese Academy of Medical Science and Peking Union Medical College, Kunming, People‘s Republic of China a

.H\:RUGV +1‡,PPXQRJHQLFLW\‡$YLDQLQÁXHQ]DYDFFLQHV‡0HWD‡$GMXYDQW $EVWUDFW Background: 7KHUH DUH VSRUDGLF FDVHV DQG ORFDO RXWEUHDNV RI +1 DYLDQ LQÁXHQ]D YLUXV worldwide every year. The World Health Organization (WHO) has paid close attention to the DYLDQ LQÁXHQ]D HSLGHPLF WUHQG $YLDQ LQÁXHQ]D YDFFLQHV $,9  DUH FRQVLGHUHG WR EH XVHIXO ZKHQDQHSLGHPLFRFFXUV+RZHYHUWKHXVHRI$,9IRUKXPDQVLVQRW\HWZLGHVSUHDGMethods: 7KLVVWXG\DVVHVVHGWKHLPPXQRJHQLFLW\DQGVDIHW\RISDQGHPLFLQÁXHQ]D+1YDFFLQHVZLWK inactivated whole virus, split virus and subunit virus vaccines for healthy adults. We searched the databases of the Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Excerpata Medica Database (EMBASE) and China National Knowledge Infrastructure (CNKI). 7KH GDWD IURP UDQGRPL]HG WULDOV UHJDUGLQJ WKH LPPXQRJHQLFLW\ DQG VDIHW\ RI $,9 ZLWK RU ZLWKRXWGLIIHUHQWW\SHVRIDGMXYDQWVIRUKHDOWK\DGXOWVZLWKDQDJHUDQJHIURPWR\HDUV  were collected. Results:$FFRUGLQJWRWKLVVWXG\WKHPRVWHIIHFWLYHGRVHVRI+1$,9UDQJHG IURPnjJWRnjJ+HPDJJOXWLQLQ (HA)DQWLJHQ$OXPLQLXPDGMXYDQWVZHUHDGPLQLVWHUHG ZLWKWKHVDPHYDFFLQHGRVHDVDQRDGMXYDQWJURXSDQGLQGXFHGWKHVDPHLPPXQHHIIHFWV +RZHYHU QRYHO DGMXYDQWV 0) DQG $6  ZHUH XVHG ZLWK D VPDOOHU GRVH RI YDFFLQH WKDQ WKH QRDGMXYDQW JURXSV DQG VXFFHVVIXOO\ VWLPXODWHG WKH ERG\ WR SURGXFH PRUH HIIHFWLYH antibodies. Conclusion:$OORIWKH+1$,9VXUYH\HGLQWKLVVWXG\ZHUHZHOOWROHUDWHGZLWKRXW serious adverse reactions. © 2016 The Author(s) Published by S. Karger AG, Basel

Introduction

Weidong Li and Guoyang Liao

Institute of Medical Biology, Chinese Academy of Medical Science and Peking Union Medical College, The 935th Jiaoling road, Kunming, Yunnan Province, Zip Code: 650118 (People's Republic of China) E-Mail [email protected] / [email protected]

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Physiol Biochem 2016;40:921-932 Cellular Physiology Cell © 2016 The Author(s). Published by S. Karger AG, Basel DOI: 10.1159/000453150 www.karger.com/cpb and Biochemistry Published online: December 07, 2016

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Downloaded by: ReadCube 75.101.163.131 - 12/7/2016 2:13:46 PM

Guo et al.: (YDOXDWLRQRI+19DFFLQH6DIHW\DQG(IÀFDF\

Physiol Biochem 2016;40:921-932 Cellular Physiology Cell © 2016 The Author(s). Published by S. Karger AG, Basel DOI: 10.1159/000453150 www.karger.com/cpb and Biochemistry Published online: December 07, 2016

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Guo et al.: (YDOXDWLRQRI+19DFFLQH6DIHW\DQG(IÀFDF\

0DWHULDOVDQG0HWKRGV Literature search and inclusion criteria ‡’‡”ˆ‘”‡†ƒŽ‹–‡”ƒ–—”‡•‡ƒ”…Š„›•‡ƒ”…Š‹‰ ˆ‘” Dzͷͳdz ƒ† Dz˜ƒ……‹‡dz —•‹‰ –Š‡ ‘…Š”ƒ‡ ‡–”ƒŽ ‡‰‹•–‡” ‘ˆ ‘–”‘ŽŽ‡† ”‹ƒŽ• ȋȌǡ ‡†Ž‹‡ǡ š…‡”’ƒ–ƒ ‡†‹…ƒ ƒ–ƒ„ƒ•‡ ȋȌ ƒ† Š‹ƒ ƒ–‹‘ƒŽ ‘™Ž‡†‰‡ ˆ”ƒ•–”—…–—”‡ ȋ Ȍ —’ –Š”‘—‰Š ’”‹Ž ʹͲͳ͸Ǥ ‘ Ž‹‹–ƒ–‹‘ ™ƒ• ’Žƒ…‡† ‘ –Š‡ Žƒ‰—ƒ‰‡ ‘” ›‡ƒ” ‘ˆ ’—„Ž‹…ƒ–‹‘Ǥ  –Š‡ ‘Ž‹‡ †ƒ–ƒ„ƒ•‡•ǡ ™‡ —•‡† –Š‡ ˆ‘ŽŽ‘™‹‰ ‡›™‘”†•ǣ ‹ϐŽ—‡œƒ ˜ƒ……‹‡ǡ ‹ƒ…–‹˜ƒ–‡† ˜ƒ……‹‡ǡ ͷͳ ƒ˜‹ƒ ‹ϐŽ—‡œƒǡ ͷͳ  ǡ ͷͳ ‹ϐŽ—‡œƒ ˜‹”—•ƒ†ͷͳŠ‹‰ŠŽ›’ƒ–Š‘‰‡‹…ƒ˜‹ƒ‹ϐŽ—‡œƒǤ ‹—Ž–ƒ‡‘—•Ž›ǡ ™‡ ƒ†‡ ƒ ‹†‡š ‘ˆ –Š‡ †‹ˆˆ‡”‡– –›’‡• ‘ˆ ƒ†Œ—˜ƒ–•Ǥ ‡ ƒŽ•‘ •‡ƒ”…Š‡† …Ž‹‹…ƒŽ–”ƒ‹Ž•Ǥ ‰‘˜ ˆ‘” ”‡“—‹”‡† ‹ˆ‘”ƒ–‹‘Ǥ ‡ …‘ŽŽ‡…–‡† ‘– ‘Ž› ’”‹ƒ”› ’—„Ž‹…ƒ–‹‘• „—– ƒŽ•‘ –Š‡‹” ”‡ˆ‡”‡…‡ Ž‹•–• ˆ‘” ƒ††‹–‹‘ƒŽ ’—„Ž‹…ƒ–‹‘•Ǥ ††‹–‹‘ƒŽŽ›ǡ ™‡ •‡ƒ”…Š‡† †ƒ–ƒ„ƒ•‡• —•‹‰ –Š‡ –‡” Dz dz –‘‰‡–Š‡” ™‹–Š –Š‡ ϐ‹”•– ƒ—–Š‘” ‘ˆ ‡ƒ…Š ƒ”–‹…Ž‡ ƒ† ‡šƒ‹‡† –Š‡ͷ‘•–”‡…‡–”‡Žƒ–‡†Ž‹•–‘ƒŽŽƒ”–‹…Ž‡•‹–Š‡ —„‡††ƒ–ƒ„ƒ•‡Ǥ Š‡‹…Ž—•‹‘…”‹–‡”‹ƒ™‡”‡•‡Ž‡…–‡†ƒ•ˆ‘ŽŽ‘™•ǣ ”ƒ†‘‹œ‡† –”‹ƒŽ• ”‡•‡ƒ”…Š ‘ˆ ͷͳ  ǡ —•‡ ‘ˆ ƒ†Œ—˜ƒ– ȋ‘” ‘–Ȍǡ •—„Œ‡…–• ƒ‰‡† ˆ”‘ ͳͺ –‘ ͸Ͳ ›‡ƒ”•‘Ž†ǡƒƒŽ›•‹•‘ˆ–Š‡…Šƒ‰‡‹ƒ–‹„‘†›Ž‡˜‡Ž•ǡ ƒ† ˜ƒ……‹‡Ǧ”‡Žƒ–‡† ƒ†˜‡”•‡ ”‡ƒ…–‹‘• ȋ‡Ǥ‰Ǥǡ ˆ‡˜‡”ǡ ”‡†‡••ǡ •Š‹˜‡”‹‰ǡ ƒŽƒ‹•‡ǡ ‡……Š›‘•‹•ǡ Ž‘…ƒŽ ’ƒ‹ ƒ†Š‡ƒ†ƒ…Š‡ȌǤ Assessment of AIV effects Š‡ ‹—‘‰‡‹…‹–› ‘ˆ   ™ƒ• ƒ••‡••‡† ƒ……‘”†‹‰ –‘ –Š‡ …”‹–‡”‹ƒ ˆ”‘ –Š‡ —”‘’‡ƒ ‡†‹…‹‡• ‰‡…› ȋȌǤ Š‡  •–ƒ–‡† –Šƒ–   …‘—Ž† „‡ ‡ˆˆ‡…–‹˜‡ ‹ˆ ‹– †‡‘•–”ƒ–‡† ‘‡ ‘ˆ –Š‡ ˆ‘ŽŽ‘™‹‰ǣ ƒ •‡”‘…‘˜‡”•‹‘ ”ƒ–‡ ε ͶͲΨ ‘” ƒ •‡”‘’”‘–‡…–‹‘ ”ƒ–‡ ε ͹ͲΨǤ Š‡ •ƒˆ‡–› ƒ••‡••‡– ‘ˆ   ‹…Ž—†‡† •›•–‡‹… ƒ† Ž‘…ƒŽ ƒ†˜‡”•‡ ‡˜‡–• ™‹–Š‹͵†ƒ›•’‘•–Ǧ˜ƒ……‹ƒ–‹‘Ǥ

Statistical analysis Š‡ †ƒ–ƒ„ƒ•‡ ™ƒ• …‘ŽŽ‡…–‡† —•‹‰ ‹…”‘•‘ˆ– š…‡ŽǤ –ƒ–ƒ ͳʹǤͲ ƒ† ‡˜ƒ ͷǤͲ •‘ˆ–™ƒ”‡ ™‡”‡ )LJŠ‡†‹ƒ‰”ƒ‘ˆ”‹•‘ˆ„‹ƒ••—ƒ”›Ǥ

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Data extraction ™‘‹†‡’‡†‡–•–ƒˆˆ‡š–”ƒ…–‡††ƒ–ƒˆ”‘ƒŽŽ ‹…Ž—†‡† •–—†‹‡•ǡ ‹…Ž—†‹‰ ˜ƒ……‹‡Ǧ”‡Žƒ–‡† ƒ†˜‡”•‡ ”‡ƒ…–‹‘•ǡƒ••‡••‡–‘ˆ‹—‘‰‡‹…‹–›ƒ†•ƒˆ‡–›ǡ —•‡ ‘ˆ ƒ†Œ—˜ƒ–•ǡ •–—†› †‡•‹‰ ƒ† ’‘’—Žƒ–‹‘ǡ ‹ϐŽ—‡œƒ ƒ–‹„‘†› †‡–‡…–‹‘ ‡–Š‘†• ƒ† –Š‡ ϐ‹”•– ƒ—–Š‘”ƒ†›‡ƒ”‘ˆ–Š‡”‡ˆ‡”‡…‡Ǥ›†‹•ƒ‰”‡‡‡–• ‘”†‹•…”‡’ƒ…‹‡•™‡”‡”‡•‘Ž˜‡†„›†‹•…—••‹‘‘”„› …‘•—Ž–‹‰ ƒ ‡š’‡”– …‘‹––‡‡ ƒ– –Š‡ •–‹–—–‡ ‘ˆ ‡†‹…ƒŽ‹‘Ž‘‰›Ǥ

Physiol Biochem 2016;40:921-932 Cellular Physiology Cell © 2016 The Author(s). Published by S. Karger AG, Basel DOI: 10.1159/000453150 www.karger.com/cpb and Biochemistry Published online: December 07, 2016

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Guo et al.: (YDOXDWLRQRI+19DFFLQH6DIHW\DQG(IÀFDF\

Downloaded by: ReadCube 75.101.163.131 - 12/7/2016 2:13:46 PM

—•‡†ˆ‘”–Š‡•–ƒ–‹•–‹…ƒŽƒƒŽ›•‡•ǤŠ‡ †‘•‡ƒ••‘…‹ƒ–‡†™‹–Šƒ†Œ—˜ƒ–—•‡™ƒ•ƒ••‡••‡†„›…ƒŽ…—Žƒ–‹‰–Š‡ ‡”‰‡””ƒ–‹‘ȋ‘††•”ƒ–‹‘ǡȌǡƒ†–Š‡ͻͷΨ…‘ϐ‹†‡…‡ƒ”‡ƒȋ…‘ϐ‹†‡…‡‹–‡”˜ƒŽǡͻͷΨ Ȍ™ƒ•‡˜ƒŽ—ƒ–‡†Ǥ —„Ž‹…ƒ–‹‘„‹ƒ•™ƒ•‡˜ƒŽ—ƒ–‡†—•‹‰–Š‡‡˜ƒͷǤͲ•‘ˆ–™ƒ”‡ƒ†‹••Š‘™‹–Š‡”‹•‘ˆ„‹ƒ••—ƒ”› †‹ƒ‰”ƒȋ ‹‰ǤͳȌǤ

Physiol Biochem 2016;40:921-932 Cellular Physiology Cell © 2016 The Author(s). Published by S. Karger AG, Basel DOI: 10.1159/000453150 www.karger.com/cpb and Biochemistry Published online: December 07, 2016

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Guo et al.: (YDOXDWLRQRI+19DFFLQH6DIHW\DQG(IÀFDF\

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5HVXOWV Selection of studies ˆ–‡”•‡ƒ”…Š‹‰‘—„‡†ǡ–Š‡Š‹ƒƒ–‹‘ƒŽ‘™Ž‡†‰‡ ˆ”ƒ•–”—…–—”‡ȋ Ȍǡ–Š‡ †ƒ–ƒ„ƒ•‡ƒ†–Š‡‘…Š”ƒ‡†ƒ–ƒ„ƒ•‡ǡ™‡ˆ‘—†͵ͷ͹ƒ”–‹…Ž‡•ǡ™Š‹…Š‹…Ž—†‡†ͳͻͳ ”‡’‡–‹–‹‘•ȋ ‹‰ǤʹȌǤ‡–Š‡„—‹Ž–ƒ†ƒ–ƒ„ƒ•‡‘ˆ‹…Ž—•‹‘”‡•‡ƒ”…ŠǤˆ–‡””‡ƒ†‹‰–Š‡ˆ—ŽŽ–‡š– ‘ˆ‘—”•—„Ǧ‰”‘—’†‹•…—••‹‘ǡ–Š‡”‡™‡”‡ʹͶ–Š‡•‡•ȏ͸Ǧͳͳǡͳ͵ǦͳͷǡͳͻǦ͵͵Ȑˆ‘…—•‹‰‘–Š‡†‘•‡ …‘•—’–‹‘ƒ†•ƒˆ‡–›‘ˆ‘˜‡Žͷͳ ǡ–™‘ƒ”–‹…Ž‡•™‹–Šƒ‹Ǧ†‡’–ŠƒƒŽ›•‹•”‡‰ƒ”†‹‰ –Š‡ …”‘••Ǧ”‡ƒ…–‹˜‡ ‹—‘‰‡‹…‹–› ‘ˆ ͷͳ   ȏ͵Ͷǡ ͵ͷȐǡ ƒ† –™‘ ƒ”–‹…Ž‡• ‘ ƒ Ž‘‰Ǧ–‡” ‹—‘‰‡‹…‹–›ƒƒŽ›•‹•‘ˆƒ˜ƒ……‹‡ƒ†–Š‡ƒ†‹‹•–”ƒ–‹‘’”‘…‡†—”‡•‘ˆƒ˜ƒ……‹‡ȏ͵͸ǡ ͵͹ȐǤ ‹ƒŽŽ›ǡ™‡‹†‡–‹ϐ‹‡†ʹͶƒ”–‹…Ž‡•…‘•‹•–‡–™‹–Š‘—”‹…Ž—•‹‘…”‹–‡”‹ƒƒ†—•‡†–Š‡ ˆ‘”–Š‡‡–ƒǦƒƒŽ›•‹•Ǥ‡„”‹‡ϐŽ›•—ƒ”‹œ‡†–Š‡…Šƒ”ƒ…–‡”‹•–‹…•‘ˆƒŽŽ–Š‡‹…Ž—†‡†•–—†‹‡• ‹ ƒ„Ž‡ ͳǤ ‘” –Š‡ ʹͶ ’—„Ž‹…ƒ–‹‘• ‘ˆ ”ƒ†‘‹œ‡† –”ƒ‹Ž•ǡ ƒŽŽ –Š‡ •—„Œ‡…–• ™‡”‡ ƒ‰‡† ˆ”‘ ͳͺ–‘͸Ͳ›‡ƒ”•ǤŠ‡–‡…Š‘Ž‘‰›ƒ†‡–Š‘†‘Ž‘‰›—•‡†ˆ‘” ƒ–‹„‘†›†‡–‡…–‹‘‹…Ž—†‡† Šƒ‡ƒ‰‰Ž—–‹‹‹Š‹„‹–‹‘ȋ Ȍƒ†–Š‡‹…”‘‡—–”ƒŽ‹œƒ–‹‘ȋȌ–‡•–Ǥ ‡ˆ‘—†ƒ†‹ˆˆ‡”‡–…‘…‡–”ƒ–‹‘‰”ƒ†‹‡–™‹–Š‹–Š‡‰”‘—’•–Šƒ–—•‡††‹ˆˆ‡”‡– †‘•‡•ǡ ™Š‹…Š‰‡‡”ƒŽŽ›—•‡†