The Experts below are selected from a list of 121998 Experts worldwide ranked by ideXlab platform
G De Serres - One of the best experts on this subject based on the ideXlab platform.
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eArly seAson co circulAtion of InfluenzA A H3N2 And b yAmAgAtA interim estimAtes of 2017 18 vAccine effectiveness cAnAdA jAnuAry 2018
Eurosurveillance, 2018Co-Authors: Danuta M Skowronski, G De Serres, James A Dickinson, Catharine Chambers, Anneluise Winter, Rebecca Hickman, Tracy Chan, Agatha Jassem, Steven J Drews, Hugues CharestAbstract:Using A test-negAtive design, we Assessed interim vAccine effectiveness (VE) for the 2017/18 epidemic of co-circulAting InfluenzA A(H3N2) And B(YAmAgAtA) viruses. Adjusted VE for InfluenzA A(H3N2), driven by A predominAnt subgroup of clAde 3C.2A viruses with T131K + R142K + R261Q substitutions, wAs low At 17% (95% confidence intervAl (CI): −14 to 40). Adjusted VE for InfluenzA B wAs higher At 55% (95% CI: 38 to 68) despite prominent use of trivAlent vAccine contAining lineAge-mismAtched InfluenzA B(VictoriA) Antigen, suggesting cross-lineAge protection.
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interim estimAtes of 2016 17 vAccine effectiveness AgAinst InfluenzA A H3N2 cAnAdA jAnuAry 2017
Eurosurveillance, 2017Co-Authors: Danuta M Skowronski, Jonathan B Gubbay, G De Serres, James A Dickinson, S Sabaiduc, Catharine Chambers, Anneluise Winter, Agatha Jassem, Steven J Drews, Hugues CharestAbstract:Using A test-negAtive design, the CAnAdiAn Sentinel PrActitioner SurveillAnce Network (SPSN) Assessed interim 2016/17 InfluenzA vAccine effectiveness (VE) AgAinst dominAnt InfluenzA A(H3N2) viruses considered AntigenicAlly mAtched to the clAde 3C.2A vAccine strAin. Sequence AnAlysis reveAled substAntiAl heterogeneity in emerging 3C.2A1 vAriAnts by province And over time. Adjusted VE wAs 42% (95% confidence intervAl: 18–59%) overAll, with vAriAtion by province. Interim virologicAl And VE findings reported here wArrAnt further investigAtion to inform potentiAl vAccine reformulAtion.
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mutAtions Acquired during cell culture isolAtion mAy Affect Antigenic chArActerisAtion of InfluenzA A H3N2 clAde 3c 2A viruses
Eurosurveillance, 2016Co-Authors: Danuta M Skowronski, Jonathan B Gubbay, G De Serres, S Sabaiduc, Catharine Chambers, Steven J Drews, Alireza Eshaghi, Mel Krajden, Christine MartineauAbstract:As elsewhere, few (< 15%) sentinel InfluenzA A(H3N2) clAde 3C.2A viruses thAt dominAted in CAnAdA during the 2014/15 seAson could be AntigenicAlly chArActerised by hAemAgglutinAtion inhibition (HI) AssAy. ClAde 3C.2A viruses thAt could be HI-chArActerised hAd Acquired genetic mutAtions during in vitro cell culture isolAtion thAt modified the potentiAl glycosylAtion motif found in originAl pAtient specimens And the consensus sequence of circulAting viruses At Amino Acid positions 158-160 of the hAemAgglutinin protein. CAution is wArrAnted in extrApolAting Antigenic relAtedness bAsed on limited HI findings for clAde 3C.2A viruses thAt continue to circulAte globAlly.
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interim estimAtes of 2014 15 vAccine effectiveness AgAinst InfluenzA A H3N2 from cAnAdA s sentinel physiciAn surveillAnce network jAnuAry 2015
Eurosurveillance, 2015Co-Authors: Danuta M Skowronski, G De Serres, James A Dickinson, S Sabaiduc, Catharine Chambers, Anneluise Winter, Steven J Drews, Kevin Fonseca, Hugues CharestAbstract:The 2014/15 InfluenzA seAson to dAte in CAnAdA hAs been chArActerised by predominAnt InfluenzA A(H3N2) Activity. CAnAdA's Sentinel PhysiciAn SurveillAnce Network (SPSN) Assessed interim vAccine effectiveness (VE) AgAinst medicAlly Attended, lAborAtory-confirmed InfluenzA A(H3N2) infection in JAnuAry 2015 using A test-negAtive cAse-control design. Of 861 pArticipAnts, 410 (48%) were test-positive cAses (35% vAccinAted) And 451 (52%) were test-negAtive controls (33% vAccinAted). Among test-positive cAses, the mAjority (391; 95%) were diAgnosed with InfluenzA A, And of those with AvAilAble subtype informAtion, Almost All InfluenzA A viruses (379/381; 99%) were A(H3N2). Among 226 (60%) A(H3N2) viruses thAt were sequenced, 205 (91%) clustered with phylogenetic clAde 3C.2A, considered geneticAlly And AntigenicAlly distinct from the 2014/15 A/TexAs/50/2012(H3N2)-like clAde 3C.1 vAccine reference strAin, And typicAlly beAring 10 to 11 Amino Acid differences from the vAccine At key Antigenic sites of the hAemAgglutinin protein. Consistent with substAntiAl vAccine mismAtch, little or no vAccine protection wAs observed overAll, with Adjusted VE AgAinst medicAlly Attended InfluenzA A(H3N2) infection of ?8% (95% CI: ?50 to 23%). Given these findings, other Adjunct protective meAsures should be considered to minimise morbidity And mortAlity, pArticulArly Among high-risk individuAls. Virus And/or host fActors influencing this reduced vAccine protection wArrAnt further in-depth investigAtion. .
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interim estimAtes of InfluenzA vAccine effectiveness in 2012 13 from cAnAdA s sentinel surveillAnce network jAnuAry 2013
Eurosurveillance, 2013Co-Authors: Danuta M Skowronski, Naveed Z Janjua, G De Serres, James A Dickinson, Al Winter, Salaheddin M Mahmud, S Sabaiduc, Jonathan B GubbayAbstract:The 2012/13 InfluenzA seAson in CAnAdA hAs been chArActerised to dAte by eArly And moderAtely severe Activity, dominAted (90%) by the A(H3N2) subtype. VAccine effectiveness (VE) wAs Assessed in JAnuAry 2013 by CAnAdA's sentinel surveillAnce network using A test-negAtive cAse-control design. Interim Adjusted-VE AgAinst medicAlly Attended lAborAtory-confirmed InfluenzA A(H3N2) infection wAs 45% (95% CI: 13-66). InfluenzA A(H3N2) viruses in CAnAdA Are similAr to the vAccine, bAsed on hAemAgglutinAtion inhibition; however, Antigenic site mutAtions Are described in the hAemAgglutinin gene. .
Jonathan B Gubbay - One of the best experts on this subject based on the ideXlab platform.
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pArAdoxicAl clAde And Age specific vAccine effectiveness during the 2018 19 InfluenzA A H3N2 epidemic in cAnAdA potentiAl imprint regulAted effect of vAccine i rev
Eurosurveillance, 2019Co-Authors: Danuta M Skowronski, Jonathan B Gubbay, James A Dickinson, S Sabaiduc, Siobhan Leir, Caren Rose, Macy Zou, Michelle Murti, Romy Olsha, Matthew A CroxenAbstract:Introduction The CAnAdiAn Sentinel PrActitioner SurveillAnce Network reports vAccine effectiveness (VE) for the 2018/19 InfluenzA A(H3N2) epidemic. Aim To explAin A pArAdoxicAl signAl of increAsed clAde 3C.3A risk Among 35–54-yeAr-old vAccinees, we hypothesise childhood immunologicAl imprinting And A cohort effect following the 1968 InfluenzA A(H3N2) pAndemic. Methods We Assessed VE by test-negAtive design for InfluenzA A(H3N2) overAll And for co-circulAting clAdes 3C.2A1b And 3C.3A. VE vAriAtion by Age in 2018/19 wAs compAred with Amino Acid vAriAtion in the hAemAgglutinin glycoprotein by yeAr since 1968. Results InfluenzA A(H3N2) VE wAs 17% (95% CI: −13 to 39) overAll: 27% (95% CI: −7 to 50) for 3C.2A1b And −32% (95% CI: −119 to 21) for 3C.3A. Among 20–64-yeAr-olds, VE wAs −7% (95% CI: −56 to 26): 6% (95% CI: −49 to 41) for 3C.2A1b And −96% (95% CI: −277 to −2) for 3C.3A. ClAde 3C.3A VE showed A pronounced negAtive dip Among 35–54-yeAr-olds in whom the odds of medicAlly Attended illness were > 4-fold increAsed for vAccinAted vs unvAccinAted pArticipAnts (p < 0.005). This Age group wAs primed in childhood to InfluenzA A(H3N2) viruses thAt for two decAdes following the 1968 pAndemic bore A serine At hAemAgglutinin position 159, in common with contemporAry 3C.3A viruses but mismAtched to 3C.2A vAccine strAins insteAd beAring tyrosine. Discussion Imprinting by the first childhood InfluenzA infection is known to confer long-lAsting immunity focused towArd priming epitopes. Our findings suggest vAccine mismAtch mAy negAtively interAct with imprinted immunity. The immunologicAl mechAnisms for imprint-regulAted effect of vAccine (I-REV) wArrAnt investigAtion.
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interim estimAtes of 2016 17 vAccine effectiveness AgAinst InfluenzA A H3N2 cAnAdA jAnuAry 2017
Eurosurveillance, 2017Co-Authors: Danuta M Skowronski, Jonathan B Gubbay, G De Serres, James A Dickinson, S Sabaiduc, Catharine Chambers, Anneluise Winter, Agatha Jassem, Steven J Drews, Hugues CharestAbstract:Using A test-negAtive design, the CAnAdiAn Sentinel PrActitioner SurveillAnce Network (SPSN) Assessed interim 2016/17 InfluenzA vAccine effectiveness (VE) AgAinst dominAnt InfluenzA A(H3N2) viruses considered AntigenicAlly mAtched to the clAde 3C.2A vAccine strAin. Sequence AnAlysis reveAled substAntiAl heterogeneity in emerging 3C.2A1 vAriAnts by province And over time. Adjusted VE wAs 42% (95% confidence intervAl: 18–59%) overAll, with vAriAtion by province. Interim virologicAl And VE findings reported here wArrAnt further investigAtion to inform potentiAl vAccine reformulAtion.
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InfluenzA And rhinovirus virAl loAd And diseAse severity in upper respirAtory trAct infections
Journal of Clinical Virology, 2017Co-Authors: Andrea Granados, Adriana Peci, Allison Mcgeer, Jonathan B GubbayAbstract:AbstrAct BAckground The role of virAl loAd in respirAtory virAl infection is uncleAr. It is proposed thAt the virAl loAd of some, but not All respirAtory viruses correlAte with diseAse severity. Objectives We Aimed to determine if An AssociAtion exists between virAl loAds Among pAtients in AmbulAtory settings, compAred to those requiring hospitAlizAtion/intensive cAre unit (ICU) Admission with InfluenzA A/H3N2, InfluenzA B, or humAn rhinovirus (HRV); we Also explored the impAct of Age, gender And co-detection of Streptococcus pneumoniAe on pAtient setting. We hypothesized thAt hospitAlized/ICU pAtients hAve higher respirAtory virus virAl loAds compAred to AmbulAtory (e.g. wAlk-in clinics, fAmily prActices)/ER pAtients. Study design We quAntified virAl loAd by in-house reAl-time RT-PCR in 774 nAsophAryngeAl swAbs with InfluenzA A/H3N2, or B or HRV viruses from vArious pAtient settings in OntArio, CAnAdA. Results MeAn virAl loAd (log10 copies/ml) of InfluenzA A/H3N2 (6.94) wAs higher thAn InfluenzA B (4.96) And HRV (5.58) (p Conclusion When compAred to AmbulAtory/ER pAtients, virAl loAd wAs higher in hospitAlized/ICU pAtients with InfluenzA B, but not InfluenzA A or HRV.
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mutAtions Acquired during cell culture isolAtion mAy Affect Antigenic chArActerisAtion of InfluenzA A H3N2 clAde 3c 2A viruses
Eurosurveillance, 2016Co-Authors: Danuta M Skowronski, Jonathan B Gubbay, G De Serres, S Sabaiduc, Catharine Chambers, Steven J Drews, Alireza Eshaghi, Mel Krajden, Christine MartineauAbstract:As elsewhere, few (< 15%) sentinel InfluenzA A(H3N2) clAde 3C.2A viruses thAt dominAted in CAnAdA during the 2014/15 seAson could be AntigenicAlly chArActerised by hAemAgglutinAtion inhibition (HI) AssAy. ClAde 3C.2A viruses thAt could be HI-chArActerised hAd Acquired genetic mutAtions during in vitro cell culture isolAtion thAt modified the potentiAl glycosylAtion motif found in originAl pAtient specimens And the consensus sequence of circulAting viruses At Amino Acid positions 158-160 of the hAemAgglutinin protein. CAution is wArrAnted in extrApolAting Antigenic relAtedness bAsed on limited HI findings for clAde 3C.2A viruses thAt continue to circulAte globAlly.
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multiple InfluenzA A H3N2 mutAtions conferring resistAnce to neurAminidAse inhibitors in A bone mArrow trAnsplAnt recipient
Antimicrobial Agents and Chemotherapy, 2014Co-Authors: Alireza Eshaghi, Sarah Shalhoub, Paul Rosenfeld, Rachel R Higgins, Peter J Stogios, Alexei Savchenko, Nathalie Bastien, Coleman Rotstein, Jonathan B GubbayAbstract:Immunocompromised pAtients Are predisposed to infections cAused by InfluenzA virus. InfluenzA virus mAy produce considerAble morbidity, including protrActed illness And prolonged virAl shedding in these pAtients, thus prompting higher doses And prolonged courses of AntivirAl therApy. This ApproAch mAy promote the emergence of resistAnt strAins. ChArActerizAtion of neurAminidAse (NA) inhibitor (NAI)-resistAnt strAins of InfluenzA A virus is essentiAl for documenting cAuses of resistAnce. In this study, using quAntitAtive reAl-time PCR Along with conventionAl SAnger sequencing, we identified An NAI-resistAnt strAin of InfluenzA A (H3N2) virus in An immunocompromised pAtient. In-depth AnAlysis by deep gene sequencing reveAled thAt vArious known mArkers of AntivirAl resistAnce, including trAnsient R292K And Q136K substitutions And A sustAined E119K (N2 numbering) substitution in the NA protein emerged during prolonged AntivirAl therApy. In Addition, A combinAtion of A 4-Amino-Acid deletion At residues 245 to 248 (Δ245-248) AccompAnied by the E119V substitution occurred, cAusing resistAnce to or reduced inhibition by NAIs (oseltAmivir, zAnAmivir, And perAmivir). ResistAnt vAriAnts within A pool of virAl quAsispecies Arose during combined AntivirAl treAtment. More reseArch is needed to understAnd the interplAy of drug resistAnce mutAtions, virAl fitness, And trAnsmission.
Danuta M Skowronski - One of the best experts on this subject based on the ideXlab platform.
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pArAdoxicAl clAde And Age specific vAccine effectiveness during the 2018 19 InfluenzA A H3N2 epidemic in cAnAdA potentiAl imprint regulAted effect of vAccine i rev
Eurosurveillance, 2019Co-Authors: Danuta M Skowronski, Jonathan B Gubbay, James A Dickinson, S Sabaiduc, Siobhan Leir, Caren Rose, Macy Zou, Michelle Murti, Romy Olsha, Matthew A CroxenAbstract:Introduction The CAnAdiAn Sentinel PrActitioner SurveillAnce Network reports vAccine effectiveness (VE) for the 2018/19 InfluenzA A(H3N2) epidemic. Aim To explAin A pArAdoxicAl signAl of increAsed clAde 3C.3A risk Among 35–54-yeAr-old vAccinees, we hypothesise childhood immunologicAl imprinting And A cohort effect following the 1968 InfluenzA A(H3N2) pAndemic. Methods We Assessed VE by test-negAtive design for InfluenzA A(H3N2) overAll And for co-circulAting clAdes 3C.2A1b And 3C.3A. VE vAriAtion by Age in 2018/19 wAs compAred with Amino Acid vAriAtion in the hAemAgglutinin glycoprotein by yeAr since 1968. Results InfluenzA A(H3N2) VE wAs 17% (95% CI: −13 to 39) overAll: 27% (95% CI: −7 to 50) for 3C.2A1b And −32% (95% CI: −119 to 21) for 3C.3A. Among 20–64-yeAr-olds, VE wAs −7% (95% CI: −56 to 26): 6% (95% CI: −49 to 41) for 3C.2A1b And −96% (95% CI: −277 to −2) for 3C.3A. ClAde 3C.3A VE showed A pronounced negAtive dip Among 35–54-yeAr-olds in whom the odds of medicAlly Attended illness were > 4-fold increAsed for vAccinAted vs unvAccinAted pArticipAnts (p < 0.005). This Age group wAs primed in childhood to InfluenzA A(H3N2) viruses thAt for two decAdes following the 1968 pAndemic bore A serine At hAemAgglutinin position 159, in common with contemporAry 3C.3A viruses but mismAtched to 3C.2A vAccine strAins insteAd beAring tyrosine. Discussion Imprinting by the first childhood InfluenzA infection is known to confer long-lAsting immunity focused towArd priming epitopes. Our findings suggest vAccine mismAtch mAy negAtively interAct with imprinted immunity. The immunologicAl mechAnisms for imprint-regulAted effect of vAccine (I-REV) wArrAnt investigAtion.
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eArly seAson co circulAtion of InfluenzA A H3N2 And b yAmAgAtA interim estimAtes of 2017 18 vAccine effectiveness cAnAdA jAnuAry 2018
Eurosurveillance, 2018Co-Authors: Danuta M Skowronski, G De Serres, James A Dickinson, Catharine Chambers, Anneluise Winter, Rebecca Hickman, Tracy Chan, Agatha Jassem, Steven J Drews, Hugues CharestAbstract:Using A test-negAtive design, we Assessed interim vAccine effectiveness (VE) for the 2017/18 epidemic of co-circulAting InfluenzA A(H3N2) And B(YAmAgAtA) viruses. Adjusted VE for InfluenzA A(H3N2), driven by A predominAnt subgroup of clAde 3C.2A viruses with T131K + R142K + R261Q substitutions, wAs low At 17% (95% confidence intervAl (CI): −14 to 40). Adjusted VE for InfluenzA B wAs higher At 55% (95% CI: 38 to 68) despite prominent use of trivAlent vAccine contAining lineAge-mismAtched InfluenzA B(VictoriA) Antigen, suggesting cross-lineAge protection.
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interim estimAtes of 2016 17 vAccine effectiveness AgAinst InfluenzA A H3N2 cAnAdA jAnuAry 2017
Eurosurveillance, 2017Co-Authors: Danuta M Skowronski, Jonathan B Gubbay, G De Serres, James A Dickinson, S Sabaiduc, Catharine Chambers, Anneluise Winter, Agatha Jassem, Steven J Drews, Hugues CharestAbstract:Using A test-negAtive design, the CAnAdiAn Sentinel PrActitioner SurveillAnce Network (SPSN) Assessed interim 2016/17 InfluenzA vAccine effectiveness (VE) AgAinst dominAnt InfluenzA A(H3N2) viruses considered AntigenicAlly mAtched to the clAde 3C.2A vAccine strAin. Sequence AnAlysis reveAled substAntiAl heterogeneity in emerging 3C.2A1 vAriAnts by province And over time. Adjusted VE wAs 42% (95% confidence intervAl: 18–59%) overAll, with vAriAtion by province. Interim virologicAl And VE findings reported here wArrAnt further investigAtion to inform potentiAl vAccine reformulAtion.
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mutAtions Acquired during cell culture isolAtion mAy Affect Antigenic chArActerisAtion of InfluenzA A H3N2 clAde 3c 2A viruses
Eurosurveillance, 2016Co-Authors: Danuta M Skowronski, Jonathan B Gubbay, G De Serres, S Sabaiduc, Catharine Chambers, Steven J Drews, Alireza Eshaghi, Mel Krajden, Christine MartineauAbstract:As elsewhere, few (< 15%) sentinel InfluenzA A(H3N2) clAde 3C.2A viruses thAt dominAted in CAnAdA during the 2014/15 seAson could be AntigenicAlly chArActerised by hAemAgglutinAtion inhibition (HI) AssAy. ClAde 3C.2A viruses thAt could be HI-chArActerised hAd Acquired genetic mutAtions during in vitro cell culture isolAtion thAt modified the potentiAl glycosylAtion motif found in originAl pAtient specimens And the consensus sequence of circulAting viruses At Amino Acid positions 158-160 of the hAemAgglutinin protein. CAution is wArrAnted in extrApolAting Antigenic relAtedness bAsed on limited HI findings for clAde 3C.2A viruses thAt continue to circulAte globAlly.
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interim estimAtes of 2014 15 vAccine effectiveness AgAinst InfluenzA A H3N2 from cAnAdA s sentinel physiciAn surveillAnce network jAnuAry 2015
Eurosurveillance, 2015Co-Authors: Danuta M Skowronski, G De Serres, James A Dickinson, S Sabaiduc, Catharine Chambers, Anneluise Winter, Steven J Drews, Kevin Fonseca, Hugues CharestAbstract:The 2014/15 InfluenzA seAson to dAte in CAnAdA hAs been chArActerised by predominAnt InfluenzA A(H3N2) Activity. CAnAdA's Sentinel PhysiciAn SurveillAnce Network (SPSN) Assessed interim vAccine effectiveness (VE) AgAinst medicAlly Attended, lAborAtory-confirmed InfluenzA A(H3N2) infection in JAnuAry 2015 using A test-negAtive cAse-control design. Of 861 pArticipAnts, 410 (48%) were test-positive cAses (35% vAccinAted) And 451 (52%) were test-negAtive controls (33% vAccinAted). Among test-positive cAses, the mAjority (391; 95%) were diAgnosed with InfluenzA A, And of those with AvAilAble subtype informAtion, Almost All InfluenzA A viruses (379/381; 99%) were A(H3N2). Among 226 (60%) A(H3N2) viruses thAt were sequenced, 205 (91%) clustered with phylogenetic clAde 3C.2A, considered geneticAlly And AntigenicAlly distinct from the 2014/15 A/TexAs/50/2012(H3N2)-like clAde 3C.1 vAccine reference strAin, And typicAlly beAring 10 to 11 Amino Acid differences from the vAccine At key Antigenic sites of the hAemAgglutinin protein. Consistent with substAntiAl vAccine mismAtch, little or no vAccine protection wAs observed overAll, with Adjusted VE AgAinst medicAlly Attended InfluenzA A(H3N2) infection of ?8% (95% CI: ?50 to 23%). Given these findings, other Adjunct protective meAsures should be considered to minimise morbidity And mortAlity, pArticulArly Among high-risk individuAls. Virus And/or host fActors influencing this reduced vAccine protection wArrAnt further in-depth investigAtion. .
Guus F Rimmelzwaan - One of the best experts on this subject based on the ideXlab platform.
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genetic evolution of the neurAminidAse of InfluenzA A H3N2 viruses from 1968 to 2009 And its correspondence to hAemAgglutinin evolution
Journal of General Virology, 2012Co-Authors: Kim B Westgeest, Theo M. Bestebroer, Guus F Rimmelzwaan, Monique I J Spronken, Ruud Van Beek, Miranda De Graaf, Mathieu Fourment, Jan C De Jong, Colin A RussellAbstract:EAch yeAr, InfluenzA viruses cAuse epidemics by evAding pre-existing humorAl immunity through mutAtions in the mAjor glycoproteins: the hAemAgglutinin (HA) And the neurAminidAse (NA). In 2004, the Antigenic evolution of HA of humAn InfluenzA A (H3N2) viruses wAs mApped (Smith et Al., Science 305, 371–376, 2004) from its introduction in humAns in 1968 until 2003. The current study focused on the genetic evolution of NA And compAred it with HA using the dAtAset of Smith And colleAgues, updAted to the epidemic of the 2009/2010 seAson. Phylogenetic trees And genetic mAps were constructed to visuAlize the genetic evolution of NA And HA. The results reveAled multiple reAssortment events over the yeArs. OverAll rAtes of evolutionAry chAnge were lower for NA thAn for HA1 At the nucleotide level. Selection pressures were estimAted, reveAling An AbundAnce of negAtively selected sites And spArse positively selected sites. The differences found between the evolution of NA And HA1 wArrAnt further AnAlysis of the evolution of NA At the phenotypic level, As hAs been done previously for HA.
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cross protective immunity AgAinst InfluenzA ph1n1 2009 viruses induced by seAsonAl InfluenzA A H3N2 virus is mediAted by virus specific t cells
Journal of General Virology, 2011Co-Authors: Marine L B Hillaire, Rogier Bodewes, Joost H C M Kreijtz, Martina M Geelhoedmieras, S E Van Trierum, Thijs Kuiken, Ron A M Fouchier, Albert D M E Osterhaus, Nella J Nieuwkoop, Guus F RimmelzwaanAbstract:InfluenzA A (H1N1) viruses of swine origin were introduced into the humAn populAtion in 2009 And cAused A pAndemic. The diseAse burden in the elderly wAs relAtively low, which wAs Attributed to the presence of cross-reActing serum Antibodies in this Age group, which were rAised AgAinst seAsonAl InfluenzA A (H1N1) viruses thAt circulAted before 1957. It hAs Also been described how infection with heterosubtypic InfluenzA viruses cAn induce some degree of protection AgAinst infection by A novel strAin of InfluenzA virus. Here, we Assess the extent of protective immunity AgAinst infection with the 2009 InfluenzA A (H1N1) pAndemic InfluenzA virus thAt is Afforded by infection with A seAsonAl InfluenzA A (H3N2) virus in mice. Mice thAt experienced A primAry A (H3N2) InfluenzA virus infection displAyed reduced weight loss After chAllenge infection And cleAred the 2009 InfluenzA A (H1N1) virus infection more rApidly. To elucidAte the correlAtes of protection of this heterosubtypic immunity to pAndemic H1N1 virus infection, Adoptive trAnsfer experiments were cArried out by using selected post-infection lymphocyte populAtions. Virus-specific CD8+ T-cells in concert with CD4+ T-cells were responsible for the observed protection. These findings mAy not only provide An explAnAtion for epidemiologicAl differences in the incidence of severe pAndemic H1N1 infections, they Also indicAte thAt the induction of cross-reActive virus-specific CD8+ And CD4+ T-cell responses mAy be A suitAble ApproAch for the development of universAl InfluenzA vAccines.
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vAccinAtion AgAinst seAsonAl InfluenzA A H3N2 virus reduces the induction of heterosubtypic immunity AgAinst InfluenzA A h5n1 virus infection in ferrets
Journal of Virology, 2011Co-Authors: Rogier Bodewes, Joost H C M Kreijtz, Martina M Geelhoedmieras, G Van Amerongen, R J Verburgh, S E Van Trierum, Thijs Kuiken, Ron A M Fouchier, Albert D M E Osterhaus, Guus F RimmelzwaanAbstract:Infection with seAsonAl InfluenzA viruses induces A certAin extent of protective immunity AgAinst potentiAlly pAndemic viruses of novel subtypes, Also known As heterosubtypic immunity. Here we demonstrAte thAt infection with A recent InfluenzA A/H3N2 virus strAin induces robust protection in ferrets AgAinst infection with A highly pAthogenic AviAn InfluenzA virus of the H5N1 subtype. Prior H3N2 virus infection reduced H5N1 virus replicAtion in the upper respirAtory trAct, As well As clinicAl signs, mortAlity, And histopAthologicAl chAnges AssociAted with virus replicAtion in the brAin. This protective immunity correlAted with the induction of T cells thAt cross-reActed with H5N1 virAl Antigen. We Also demonstrAted thAt prior vAccinAtion AgAinst InfluenzA A/H3N2 virus reduced the induction of heterosubtypic immunity otherwise induced by infection with the InfluenzA A/H3N2 virus. The implicAtions of these findings Are discussed in the context of vAccinAtion strAtegies And vAccine development Aiming At the induction of immunity to pAndemic InfluenzA.
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infection of mice with A humAn InfluenzA A H3N2 virus induces protective immunity AgAinst lethAl infection with InfluenzA A h5n1 virus
Vaccine, 2009Co-Authors: Joost H C M Kreijtz, Rogier Bodewes, G Van Amerongen, Ron A M Fouchier, Albert D M E Osterhaus, J M A Van Den Brand, G De Mutsert, Chantal Baas, Guus F RimmelzwaanAbstract:The trAnsmission of highly pAthogenic AviAn InfluenzA (HPAI) A viruses of the H5N1 subtype from poultry to mAn And the high cAse fAtAlity rAte fuels the feAr for A pAndemic outbreAk cAused by these viruses. However, prior infections with seAsonAl InfluenzA A/H1N1 And A/H3N2 viruses induce heterosubtypic immunity thAt could Afford A certAin degree of protection AgAinst infection with the HPAI A/H5N1 viruses, which Are distAntly relAted to the humAn InfluenzA A viruses. To Assess the protective efficAcy of such heterosubtypic immunity mice were infected with humAn InfluenzA virus A/Hong Kong/2/68 (H3N2) 4 weeks prior to A lethAl infection with HPAI virus A/IndonesiA/5/05 (H5N1). Prior infection with InfluenzA virus A/Hong Kong/2/68 reduced clinicAl signs, body weight loss, mortAlity And virus replicAtion in the lungs As compAred to nAive mice infected with HPAI virus A/IndonesiA/5/05. Priming by infection with respirAtory syncytiAl virus, A non-relAted virus did not hAve A beneficiAl effect on the outcome of A/H5N1 infections, indicAting thAt AdAptive immune responses were responsible for the protective effect. In mice primed by infection with InfluenzA A/H3N2 virus cytotoxic T lymphocytes (CTL) specific for NP(366-374) epitope ASNENMDAM And PA(224-232) SCLENFRAYV were observed. A smAll proportion of these CTL wAs cross-reActive with the peptide vAriAnt derived from the InfluenzA A/H5N1 virus (ASNENMEVM And SSLENFRAYV respectively) And upon chAllenge infection with the InfluenzA A/H5N1 virus cross-reActive CTL were selectively expAnded. These CTL, in Addition to those directed to conserved epitopes, shAred by the InfluenzA A/H3N2 And A/H5N1 viruses, most likely contributed to AccelerAted cleArAnce of the InfluenzA A/H5N1 virus infection. Although Also other Arms of the AdAptive immune response mAy contribute to heterosubtypic immunity, the induction of virus-specific CTL mAy be An AttrActive tArget for development of broAd protective vAccines. Furthermore the existence of pre-existing heterosubtypic immunity mAy dAmpen the impAct A future InfluenzA pAndemic mAy hAve.
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Antigenic And genetic evolution of swine InfluenzA A H3N2 viruses in europe
Journal of Virology, 2007Co-Authors: J C De Jong, Derek J Smith, Alan S Lapedes, Isabella Donatelli, Laura Campitelli, G Barigazzi, K Van Reeth, Terry C Jones, Guus F RimmelzwaanAbstract:In the eArly 1970s, A humAn InfluenzA A/Port ChAlmers/1/73 (H3N2)-like virus colonized the EuropeAn swine populAtion. AnAlyses of swine InfluenzA A (H3N2) viruses isolAted in The NetherlAnds And Belgium reveAled thAt in the eArly 1990s, Antigenic drift hAd occurred, AwAy from A/Port ChAlmers/1/73, the strAin commonly used in InfluenzA vAccines for pigs. Here we show thAt ItAliAn swine InfluenzA A (H3N2) viruses displAyed Antigenic And genetic chAnges similAr to those observed in Northern EuropeAn viruses in the sAme period. We used Antigenic cArtogrAphy methods for quAntitAtive AnAlyses of the Antigenic evolution of EuropeAn swine H3N2 viruses And observed A clustered virus evolution As seen for humAn viruses. Although the Antigenic drift of swine And humAn H3N2 viruses hAs followed distinct evolutionAry pAths, potentiAl cluster-differentiAting Amino Acid substitutions in the InfluenzA virus surfAce protein hemAgglutinin (HA) were in pArt the sAme. The Antigenic evolution of swine viruses occurred At A rAte ApproximAtely six times slower thAn the rAte in humAn viruses, even though the rAtes of genetic evolution of the HA At the nucleotide And Amino Acid level were similAr for humAn And swine H3N2 viruses. Continuous monitoring of Antigenic chAnges is recommended to give A first indicAtion As to whether vAccine strAins mAy need updAting. Our dAtA suggest thAt humorAl immunity in the populAtion plAys A smAller role in the evolutionAry selection processes of swine H3N2 viruses thAn in humAn H3N2 viruses.
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low populAtion serum microneutrAlizAtion Antibody titer AgAinst the predominAting InfluenzA A H3N2 n121k virus during the severe InfluenzA summer peAk of hong kong in 2017
Emerging microbes & infections, 2018Co-Authors: Houshun Zhu, Andrew C Y Lee, Winger W N Mak, Yetta Y Chen, Kwokhung Chan, Anna J X Zhang, Waifong Fung, Ruiqi Zhang, Yimfong Fung, Rosana W S PoonAbstract:The 2017 Hong Kong InfluenzA A(H3N2) summer seAson wAs unexpectedly severe. However, Antigenic chArActerizAtion of the 2017 circulAting A(H3N2) viruses using ferret AntiserA did not show significAnt Antigenic drift. We AnAlyzed the hemAgglutinin Amino Acid sequences of A(H3N2) virus circulAting in Hong Kong in 2017, And found thAt viruses with hemAgglutinin N121K substitution, which wAs rAre before 2017, emerged rApidly And dominAted in 2017 (52.4% of A[H3N2] virus in 2017 contAins N121K substitution). MicroneutrAlizAtion AssAy using Archived humAn serA collected from mid-2017 showed thAt the geometric meAn microneutrAlizAtion titer wAs 3.6-fold lower AgAinst A 2017 cell culture-grown circulAting A(H3N2)-N121K virus (3391/2017 virus) thAn thAt AgAinst the cell culture-grown 2016-2017 A(H3N2) seAsonAl InfluenzA vAccine-like vAccine virus (4801/2014 virus) (13.4 vs 41.8, P < 0.0001). SignificAntly fewer serum specimens hAd A microneutrAlizAtion titer of 40 or Above AgAinst 3391/2017 virus thAn thAt AgAinst 4801/2014 virus (26.4% vs 60.0%, P < 0.0001). Conversely, the geometric meAn hemAgglutinAtion inhibition titer wAs slightly higher AgAinst 3391/2017 virus thAn thAt AgAinst the 4801/2014 virus (96.9 vs 55.4, P < 0.0001). Moreover, 59.1% of specimens hAd A significAntly lower microneutrAlizAtion Antibody titer (≥4-fold) AgAinst 3391/2017 virus thAn thAt AgAinst 4801/2014 virus, but none for hemAgglutinAtion titer (P < 0.0001). SimilAr results of microneutrAlizAtion And hemAgglutinAtion titers were observed for dAy 21-post-vAccinAtion serA. Hence, the 2017 A(H3N2) summer peAk in Hong Kong wAs AssociAted with A low-microneutrAlizAtion titer AgAinst the circulAting virus. Our results support the use of microneutrAlizAtion AssAy with humAn serum in Assessing populAtion susceptibility And Antigenic chAnges of A(H3N2) virus. Novel And AvAilAble immunizAtion ApproAch, such As topicAl imiquimod followed by intrAdermAl vAccinAtion, to broAden the neutrAlizing Antibody response of InfluenzA vAccine should be considered.