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D. Krysan (2004)
Effectiveness of inactivated influenza vaccine in preventing acute otitis media in young children: a randomized controlled trial.The Journal of pediatrics, 144 3
A. Jansen, E. Sanders, A. Hoes, A. Loon, E. Hak (2008)
Effects of Influenza Plus Pneumococcal Conjugate Vaccination Versus Influenza Vaccination Alone in Preventing Respiratory Tract Infections in Children: A Randomized, Double-Blind, Placebo-Controlled TrialThe Journal of Pediatrics, 153
Andrew Dunning (2006)
A model for immunological correlates of protectionStatistics in Medicine, 25
P. Gilbert, Y. Fong, M. Juraska, Lindsay Carpp, A. Monto, E. Martin, J. Petrie (2019)
HAI and NAI titer correlates of inactivated and live attenuated influenza vaccine efficacyBMC Infectious Diseases, 19
W. Barlow (1994)
Robust variance estimation for the case-cohort design.Biometrics, 50 4
( Siber GR , ChangI, BakerS, et al. Estimating the protective concentration of anti-pneumococcal capsular polysaccharide antibodies. Vaccine2007; 25:3816–26.17368878)
Siber GR , ChangI, BakerS, et al. Estimating the protective concentration of anti-pneumococcal capsular polysaccharide antibodies. Vaccine2007; 25:3816–26.17368878Siber GR , ChangI, BakerS, et al. Estimating the protective concentration of anti-pneumococcal capsular polysaccharide antibodies. Vaccine2007; 25:3816–26.17368878, Siber GR , ChangI, BakerS, et al. Estimating the protective concentration of anti-pneumococcal capsular polysaccharide antibodies. Vaccine2007; 25:3816–26.17368878
M. Rolfes, D. Goswami, A. Sharmeen, S. Yeasmin, Nasrin Parvin, K. Nahar, Mustafizur Rahman, M. Barends, D. Ahmed, M. Rahman, J. Bresee, S. Luby, L. Moulton, M. Santosham, A. Fry, W. Brooks (2017)
Efficacy of trivalent influenza vaccine against laboratory-confirmed influenza among young children in a randomized trial in BangladeshVaccine, 35
(2010)
Relationship between haemagglutinationinhibiting antibody titres and clinical protection against influenza: development and application of a Bayesian random-effects model
( Plotkin SA . Vaccines: correlates of vaccine-induced immunity. Clin Infect Dis2008; 47:401–9.18558875)
Plotkin SA . Vaccines: correlates of vaccine-induced immunity. Clin Infect Dis2008; 47:401–9.18558875Plotkin SA . Vaccines: correlates of vaccine-induced immunity. Clin Infect Dis2008; 47:401–9.18558875, Plotkin SA . Vaccines: correlates of vaccine-induced immunity. Clin Infect Dis2008; 47:401–9.18558875
( Claeys C , ZamanK, DbaiboG, et al; Flu4VEC Study Group.Prevention of vaccine-matched and mismatched influenza in children aged 6-35 months: a multinational randomised trial across five influenza seasons. Lancet Child Adolesc Health2018; 2:338–49.30169267)
Claeys C , ZamanK, DbaiboG, et al; Flu4VEC Study Group.Prevention of vaccine-matched and mismatched influenza in children aged 6-35 months: a multinational randomised trial across five influenza seasons. Lancet Child Adolesc Health2018; 2:338–49.30169267Claeys C , ZamanK, DbaiboG, et al; Flu4VEC Study Group.Prevention of vaccine-matched and mismatched influenza in children aged 6-35 months: a multinational randomised trial across five influenza seasons. Lancet Child Adolesc Health2018; 2:338–49.30169267, Claeys C , ZamanK, DbaiboG, et al; Flu4VEC Study Group.Prevention of vaccine-matched and mismatched influenza in children aged 6-35 months: a multinational randomised trial across five influenza seasons. Lancet Child Adolesc Health2018; 2:338–49.30169267
S. Plotkin (2008)
Vaccines: correlates of vaccine-induced immunity.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 47 3
S. Black, U. Nicolay, T. Vesikari, M. Knuf, G. Giudice, G. Cioppa, T. Tsai, R. Clemens, R. Rappuoli (2011)
Hemagglutination Inhibition Antibody Titers as a Correlate of Protection for Inactivated Influenza Vaccines in ChildrenThe Pediatric Infectious Disease Journal, 30
Andrew Dunning, C. Diazgranados, T. Voloshen, Branda Hu, V. Landolfi, H. Talbot (2016)
Correlates of Protection against Influenza in the Elderly: Results from an Influenza Vaccine Efficacy TrialClinical and Vaccine Immunology : CVI, 23
( Prentice RL . Surrogate endpoints in clinical trials: definition and operational criteria. Stat Med1989; 8:431–40.2727467)
Prentice RL . Surrogate endpoints in clinical trials: definition and operational criteria. Stat Med1989; 8:431–40.2727467Prentice RL . Surrogate endpoints in clinical trials: definition and operational criteria. Stat Med1989; 8:431–40.2727467, Prentice RL . Surrogate endpoints in clinical trials: definition and operational criteria. Stat Med1989; 8:431–40.2727467
P. Nguipdop-Djomo, Sara Thomas, P. Fine (2013)
Correlates of vaccine-induced protection: methods and implications
( Coudeville L , BailleuxF, RicheB, et al. Relationship between haemagglutination-inhibiting antibody titres and clinical protection against influenza: development and application of a Bayesian random-effects model. BMC Med Res Methodol2010; 10:18.20210985)
Coudeville L , BailleuxF, RicheB, et al. Relationship between haemagglutination-inhibiting antibody titres and clinical protection against influenza: development and application of a Bayesian random-effects model. BMC Med Res Methodol2010; 10:18.20210985Coudeville L , BailleuxF, RicheB, et al. Relationship between haemagglutination-inhibiting antibody titres and clinical protection against influenza: development and application of a Bayesian random-effects model. BMC Med Res Methodol2010; 10:18.20210985, Coudeville L , BailleuxF, RicheB, et al. Relationship between haemagglutination-inhibiting antibody titres and clinical protection against influenza: development and application of a Bayesian random-effects model. BMC Med Res Methodol2010; 10:18.20210985
( Ng S , FangVJ, IpDK, et al. Estimation of the association between antibody titers and protection against confirmed influenza virus infection in children. J Infect Dis2013; 208:1320–4.23908481)
Ng S , FangVJ, IpDK, et al. Estimation of the association between antibody titers and protection against confirmed influenza virus infection in children. J Infect Dis2013; 208:1320–4.23908481Ng S , FangVJ, IpDK, et al. Estimation of the association between antibody titers and protection against confirmed influenza virus infection in children. J Infect Dis2013; 208:1320–4.23908481, Ng S , FangVJ, IpDK, et al. Estimation of the association between antibody titers and protection against confirmed influenza virus infection in children. J Infect Dis2013; 208:1320–4.23908481
D. Hobson, R. Curry, A. Beare, A. Ward-Gardner (1972)
The role of serum haemagglutination-inhibiting antibody in protection against challenge infection with influenza A2 and B virusesEpidemiology and Infection, 70
Taro Maeda, Yukihiro Shintani, Kanako Nakano, Kazuhiro Terashima, Yoshiyasu Yamada (2004)
Failure of inactivated influenza A vaccine to protect healthy children aged 6−24 monthsPediatrics International, 46
( World Health Organization. Correlates of vaccine-induced protection: methods and implications. WHO/IVB/13.01. 2013. https://apps.who.int/iris/bitstream/handle/10665/84288/WHO_IVB_13.01_eng.pdf.)
World Health Organization. Correlates of vaccine-induced protection: methods and implications. WHO/IVB/13.01. 2013. https://apps.who.int/iris/bitstream/handle/10665/84288/WHO_IVB_13.01_eng.pdf.World Health Organization. Correlates of vaccine-induced protection: methods and implications. WHO/IVB/13.01. 2013. https://apps.who.int/iris/bitstream/handle/10665/84288/WHO_IVB_13.01_eng.pdf., World Health Organization. Correlates of vaccine-induced protection: methods and implications. WHO/IVB/13.01. 2013. https://apps.who.int/iris/bitstream/handle/10665/84288/WHO_IVB_13.01_eng.pdf.
( Rolfes MA , GoswamiD, SharmeenAT, et al. Efficacy of trivalent influenza vaccine against laboratory-confirmed influenza among young children in a randomized trial in Bangladesh. Vaccine2017; 35:6967–76.29100706)
Rolfes MA , GoswamiD, SharmeenAT, et al. Efficacy of trivalent influenza vaccine against laboratory-confirmed influenza among young children in a randomized trial in Bangladesh. Vaccine2017; 35:6967–76.29100706Rolfes MA , GoswamiD, SharmeenAT, et al. Efficacy of trivalent influenza vaccine against laboratory-confirmed influenza among young children in a randomized trial in Bangladesh. Vaccine2017; 35:6967–76.29100706, Rolfes MA , GoswamiD, SharmeenAT, et al. Efficacy of trivalent influenza vaccine against laboratory-confirmed influenza among young children in a randomized trial in Bangladesh. Vaccine2017; 35:6967–76.29100706
( Maeda T , ShintaniY, NakanoK, et al. Failure of inactivated influenza A vaccine to protect healthy children aged 6-24 months. Pediatr Int2004; 46:122–5.15056235)
Maeda T , ShintaniY, NakanoK, et al. Failure of inactivated influenza A vaccine to protect healthy children aged 6-24 months. Pediatr Int2004; 46:122–5.15056235Maeda T , ShintaniY, NakanoK, et al. Failure of inactivated influenza A vaccine to protect healthy children aged 6-24 months. Pediatr Int2004; 46:122–5.15056235, Maeda T , ShintaniY, NakanoK, et al. Failure of inactivated influenza A vaccine to protect healthy children aged 6-24 months. Pediatr Int2004; 46:122–5.15056235
E. Hurwitz, M. Haber, A. Chang, T. Shope, S. Teo, J. Giesick, M. Ginsberg, N. Cox (2000)
Studies of the 1996-1997 inactivated influenza vaccine among children attending day care: immunologic response, protection against infection, and clinical effectiveness.The Journal of infectious diseases, 182 4
L. Freedman, B. Graubard, A. Schatzkin (1992)
Statistical validation of intermediate endpoints for chronic diseases.Statistics in medicine, 11 2
( Hoberman A , GreenbergDP, ParadiseJL, et al. Effectiveness of inactivated influenza vaccine in preventing acute otitis media in young children: a randomized controlled trial. JAMA2003; 290:1608–16.14506120)
Hoberman A , GreenbergDP, ParadiseJL, et al. Effectiveness of inactivated influenza vaccine in preventing acute otitis media in young children: a randomized controlled trial. JAMA2003; 290:1608–16.14506120Hoberman A , GreenbergDP, ParadiseJL, et al. Effectiveness of inactivated influenza vaccine in preventing acute otitis media in young children: a randomized controlled trial. JAMA2003; 290:1608–16.14506120, Hoberman A , GreenbergDP, ParadiseJL, et al. Effectiveness of inactivated influenza vaccine in preventing acute otitis media in young children: a randomized controlled trial. JAMA2003; 290:1608–16.14506120
( Dunning AJ . A model for immunological correlates of protection. Stat Med2006; 25:1485–97.16158409)
Dunning AJ . A model for immunological correlates of protection. Stat Med2006; 25:1485–97.16158409Dunning AJ . A model for immunological correlates of protection. Stat Med2006; 25:1485–97.16158409, Dunning AJ . A model for immunological correlates of protection. Stat Med2006; 25:1485–97.16158409
( Vesikari T , KnufM, WutzlerP, et al. Oil-in-water emulsion adjuvant with influenza vaccine in young children. N Engl J Med2011; 365:1406–16.21995388)
Vesikari T , KnufM, WutzlerP, et al. Oil-in-water emulsion adjuvant with influenza vaccine in young children. N Engl J Med2011; 365:1406–16.21995388Vesikari T , KnufM, WutzlerP, et al. Oil-in-water emulsion adjuvant with influenza vaccine in young children. N Engl J Med2011; 365:1406–16.21995388, Vesikari T , KnufM, WutzlerP, et al. Oil-in-water emulsion adjuvant with influenza vaccine in young children. N Engl J Med2011; 365:1406–16.21995388
( Qin L , GilbertPB, CoreyL, et al. A framework for assessing immunological correlates of protection in vaccine trials. J Infect Dis2007; 196:1304–12.17922394)
Qin L , GilbertPB, CoreyL, et al. A framework for assessing immunological correlates of protection in vaccine trials. J Infect Dis2007; 196:1304–12.17922394Qin L , GilbertPB, CoreyL, et al. A framework for assessing immunological correlates of protection in vaccine trials. J Infect Dis2007; 196:1304–12.17922394, Qin L , GilbertPB, CoreyL, et al. A framework for assessing immunological correlates of protection in vaccine trials. J Infect Dis2007; 196:1304–12.17922394
( de Jong JC , PalacheAM, BeyerWE, et al. Haemagglutination-inhibiting antibody to influenza virus. Dev Biol (Basel)2003; 115:63–73.15088777)
de Jong JC , PalacheAM, BeyerWE, et al. Haemagglutination-inhibiting antibody to influenza virus. Dev Biol (Basel)2003; 115:63–73.15088777de Jong JC , PalacheAM, BeyerWE, et al. Haemagglutination-inhibiting antibody to influenza virus. Dev Biol (Basel)2003; 115:63–73.15088777, de Jong JC , PalacheAM, BeyerWE, et al. Haemagglutination-inhibiting antibody to influenza virus. Dev Biol (Basel)2003; 115:63–73.15088777
( Gilbert PB , FongY, JuraskaM, et al. HAI and NAI titer correlates of inactivated and live attenuated influenza vaccine efficacy. BMC Infect Dis2019; 19:453.31117986)
Gilbert PB , FongY, JuraskaM, et al. HAI and NAI titer correlates of inactivated and live attenuated influenza vaccine efficacy. BMC Infect Dis2019; 19:453.31117986Gilbert PB , FongY, JuraskaM, et al. HAI and NAI titer correlates of inactivated and live attenuated influenza vaccine efficacy. BMC Infect Dis2019; 19:453.31117986, Gilbert PB , FongY, JuraskaM, et al. HAI and NAI titer correlates of inactivated and live attenuated influenza vaccine efficacy. BMC Infect Dis2019; 19:453.31117986
J. Robins, A. Rotnitzky, L. Zhao (1994)
Estimation of Regression Coefficients When Some Regressors are not Always ObservedJournal of the American Statistical Association, 89
R. Prentice (1989)
Surrogate endpoints in clinical trials: definition and operational criteria.Statistics in medicine, 8 4
( Hurwitz ES , HaberM, ChangA, et al. Studies of the 1996-1997 inactivated influenza vaccine among children attending day care: immunologic response, protection against infection, and clinical effectiveness. J Infect Dis2000; 182:1218–21.10979921)
Hurwitz ES , HaberM, ChangA, et al. Studies of the 1996-1997 inactivated influenza vaccine among children attending day care: immunologic response, protection against infection, and clinical effectiveness. J Infect Dis2000; 182:1218–21.10979921Hurwitz ES , HaberM, ChangA, et al. Studies of the 1996-1997 inactivated influenza vaccine among children attending day care: immunologic response, protection against infection, and clinical effectiveness. J Infect Dis2000; 182:1218–21.10979921, Hurwitz ES , HaberM, ChangA, et al. Studies of the 1996-1997 inactivated influenza vaccine among children attending day care: immunologic response, protection against infection, and clinical effectiveness. J Infect Dis2000; 182:1218–21.10979921
(2018)
Flu4VEC Study Group. Prevention of vaccine-matched and mismatched influenza in children aged 6-35 months: a multinational randomised trial across five influenza
( Barlow WE . Robust variance estimation for the case-cohort design. Biometrics1994; 50:1064–72.7786988)
Barlow WE . Robust variance estimation for the case-cohort design. Biometrics1994; 50:1064–72.7786988Barlow WE . Robust variance estimation for the case-cohort design. Biometrics1994; 50:1064–72.7786988, Barlow WE . Robust variance estimation for the case-cohort design. Biometrics1994; 50:1064–72.7786988
S. Plotkin, P. Gilbert (2012)
Nomenclature for immune correlates of protection after vaccination.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 54 11
( Robins J , RotnitzkyA, ZhaoL. Estimation of regression coefficients when some regressors are not always observed. J Am Stat Assoc1994; 89:846–66.)
Robins J , RotnitzkyA, ZhaoL. Estimation of regression coefficients when some regressors are not always observed. J Am Stat Assoc1994; 89:846–66.Robins J , RotnitzkyA, ZhaoL. Estimation of regression coefficients when some regressors are not always observed. J Am Stat Assoc1994; 89:846–66., Robins J , RotnitzkyA, ZhaoL. Estimation of regression coefficients when some regressors are not always observed. J Am Stat Assoc1994; 89:846–66.
T. Vesikari, M. Knuf, P. Wutzler, A. Karvonen, D. Kieninger-Baum, H. Schmitt, F. Baehner, A. Borkowski, T. Tsai, R. Clemens (2011)
Oil-in-water emulsion adjuvant with influenza vaccine in young children.The New England journal of medicine, 365 15
( Black S , NicolayU, VesikariT, et al. Hemagglutination inhibition antibody titers as a correlate of protection for inactivated influenza vaccines in children. Pediatr Infect Dis J2011; 30:1081–5.21983214)
Black S , NicolayU, VesikariT, et al. Hemagglutination inhibition antibody titers as a correlate of protection for inactivated influenza vaccines in children. Pediatr Infect Dis J2011; 30:1081–5.21983214Black S , NicolayU, VesikariT, et al. Hemagglutination inhibition antibody titers as a correlate of protection for inactivated influenza vaccines in children. Pediatr Infect Dis J2011; 30:1081–5.21983214, Black S , NicolayU, VesikariT, et al. Hemagglutination inhibition antibody titers as a correlate of protection for inactivated influenza vaccines in children. Pediatr Infect Dis J2011; 30:1081–5.21983214
J. Jong, A. Palache, W. Beyer, G. Rimmelzwaan, A. Boon, A. Osterhaus (2003)
Haemagglutination-inhibiting antibody to influenza virus.Developments in biologicals, 115
J. Sadoff, J. Wittes, L. Qin, P. Gilbert, L. Corey, M. McElrath, S. Self (2007)
A framework for assessing immunological correlates of protection in vaccine trials.The Journal of infectious diseases, 196 9
( Jansen AG , SandersEA, HoesAW, et al. Effects of influenza plus pneumococcal conjugate vaccination versus influenza vaccination alone in preventing respiratory tract infections in children: a randomized, double-blind, placebo-controlled trial. J Pediatr2008; 153:764–70.18621393)
Jansen AG , SandersEA, HoesAW, et al. Effects of influenza plus pneumococcal conjugate vaccination versus influenza vaccination alone in preventing respiratory tract infections in children: a randomized, double-blind, placebo-controlled trial. J Pediatr2008; 153:764–70.18621393Jansen AG , SandersEA, HoesAW, et al. Effects of influenza plus pneumococcal conjugate vaccination versus influenza vaccination alone in preventing respiratory tract infections in children: a randomized, double-blind, placebo-controlled trial. J Pediatr2008; 153:764–70.18621393, Jansen AG , SandersEA, HoesAW, et al. Effects of influenza plus pneumococcal conjugate vaccination versus influenza vaccination alone in preventing respiratory tract infections in children: a randomized, double-blind, placebo-controlled trial. J Pediatr2008; 153:764–70.18621393
( Freedman LS , GraubardBI, SchatzkinA. Statistical validation of intermediate endpoints for chronic diseases. Stat Med1992; 11:167–78.1579756)
Freedman LS , GraubardBI, SchatzkinA. Statistical validation of intermediate endpoints for chronic diseases. Stat Med1992; 11:167–78.1579756Freedman LS , GraubardBI, SchatzkinA. Statistical validation of intermediate endpoints for chronic diseases. Stat Med1992; 11:167–78.1579756, Freedman LS , GraubardBI, SchatzkinA. Statistical validation of intermediate endpoints for chronic diseases. Stat Med1992; 11:167–78.1579756
( Hobson D , CurryRL, BeareAS, Ward-GardnerA. The role of serum haemagglutination-inhibiting antibody in protection against challenge infection with influenza A2 and B viruses. J Hyg1972; 70:767–77.)
Hobson D , CurryRL, BeareAS, Ward-GardnerA. The role of serum haemagglutination-inhibiting antibody in protection against challenge infection with influenza A2 and B viruses. J Hyg1972; 70:767–77.Hobson D , CurryRL, BeareAS, Ward-GardnerA. The role of serum haemagglutination-inhibiting antibody in protection against challenge infection with influenza A2 and B viruses. J Hyg1972; 70:767–77., Hobson D , CurryRL, BeareAS, Ward-GardnerA. The role of serum haemagglutination-inhibiting antibody in protection against challenge infection with influenza A2 and B viruses. J Hyg1972; 70:767–77.
G. Siber, I. Chang, S. Baker, P. Fernsten, K. O'Brien, M. Santosham, K. Klugman, S. Madhi, P. Paradiso, R. Kohberger (2007)
Estimating the protective concentration of anti-pneumococcal capsular polysaccharide antibodies.Vaccine, 25 19
Carine Claeys, K. Zaman, G. Dbaibo, Ping Li, A. Izu, P. Kosalaraksa, Luis Rivera, B. Acosta, M. BASANTA, A. Aziz, Miguel Cabanero, Vijayalakshmi Chandrashekaran, B. Corsaro, Luis Cousin, Adolfo Diaz, J. Díez-Domingo, E. Dinleyici, S. Faust, D. Friel, J. Garcia-Sicilia, G. Gomez-Go, Maria Gonzales, S. Hughes, T. Jackowska, S. Kant, M. Lucero, Ludovic Malvaux, J. Bermúdez, F. Martinón-Torres, Mariano Miranda, May Montellano, Maria Sambola, R. Prymula, T. Puthanakit, Renáta Růžková, I. Sadowska-Krawczenko, Ignacio Cueva, E. Sokal, Jyoti Soni, H. Szymański, À. Ulied, A. Schuind, Varsha Jain, B. Innis (2018)
Prevention of vaccine-matched and mismatched influenza in children aged 6-35 months: a multinational randomised trial across five influenza seasons.The Lancet. Child & adolescent health, 2 5
S. Ng, V. Fang, D. Ip, Kwok-Hung Chan, G. Leung, J. Peiris, B. Cowling (2013)
Estimation of the association between antibody titers and protection against confirmed influenza virus infection in children.The Journal of infectious diseases, 208 8
BackgroundData from a randomized controlled efficacy trial of an inactivated quadrivalent influenza vaccine in children 6–35 months of age were used to determine whether hemagglutination inhibition (HI) antibody titer against A/H1N1 and A/H3N2 is a statistical correlate of protection (CoP) for the risk of reverse-transcription polymerase chain reaction (RT-PCR)–confirmed influenza associated with the corresponding strain.MethodsThe Prentice criteria were used to statistically validate strain-specific HI antibody titer as a CoP. The probability of protection was identified using the Dunning model corresponding to a prespecified probability of protection at an individual level. The group-level protective threshold was identified using the Siber approach, leading to unbiased predicted vaccine efficacy (VE). A case-cohort subsample was used for this exploratory analysis.ResultsPrentice criteria confirmed that HI titer is a statistical CoP for RT-PCR–confirmed influenza. The Dunning model predicted a probability of protection of 49.7% against A/H1N1 influenza and 54.7% against A/H3N2 influenza at an HI antibody titer of 1:40 for the corresponding strain. Higher titers of 1:320 were associated with >80% probability of protection. The Siber method predicted VE of 61.0% at a threshold of 1:80 for A/H1N1 and 46.6% at 1:113 for A/H3N2.ConclusionsThe study validated HI antibody titer as a statistical CoP, by demonstrating that HI titer is correlated with clinical protection against RT-PCR–confirmed influenza associated with the corresponding influenza strain and is predictive of VE in children 6–35 months of age.Clinical Trials RegistrationNCT01439360.
Open Forum Infectious Diseases – Oxford University Press
Published: Sep 25, 2021
Keywords: HI antibodies; correlate of protection; influenza; children
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