tetano
Editor, Senior Moderator
Open Forum Infect Dis
. 2021 Sep 25;9(2)
fab477.
doi: 10.1093/ofid/ofab477. eCollection 2022 Feb.
Association Between Hemagglutination Inhibition Antibody Titers and Protection Against Reverse-Transcription Polymerase Chain Reaction-Confirmed Influenza Illness in Children 6-35 Months of Age: Statistical Evaluation of a Correlate of Protection
Jasur Danier[SUP] 1 [/SUP], Andrea Callegaro[SUP] 2 [/SUP], Jyoti Soni[SUP] 3 [/SUP], Alfoso Carmona[SUP] 4 [/SUP], Pope Kosalaraska[SUP] 5 [/SUP], Luis Rivera[SUP] 6 [/SUP], Damien Friel[SUP] 7 [/SUP], Wenji Pu[SUP] 1 [/SUP], Valerie Vantomme[SUP] 2 [/SUP], Ghassan Dbaibo[SUP] 8 [/SUP], Bruce L Innis[SUP] 9 [/SUP], Anne Schuind[SUP] 1 [/SUP], Khalequ Zaman[SUP] 10 [/SUP], Jerome Wilson[SUP] 1 [/SUP]
Affiliations
Abstract
Background: Data 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.
Methods: The 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.
Results: Prentice 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.
Conclusions: The 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 registration: NCT01439360.
Keywords: HI antibodies; children; correlate of protection; influenza.
. 2021 Sep 25;9(2)
fab477.doi: 10.1093/ofid/ofab477. eCollection 2022 Feb.
Association Between Hemagglutination Inhibition Antibody Titers and Protection Against Reverse-Transcription Polymerase Chain Reaction-Confirmed Influenza Illness in Children 6-35 Months of Age: Statistical Evaluation of a Correlate of Protection
Jasur Danier[SUP] 1 [/SUP], Andrea Callegaro[SUP] 2 [/SUP], Jyoti Soni[SUP] 3 [/SUP], Alfoso Carmona[SUP] 4 [/SUP], Pope Kosalaraska[SUP] 5 [/SUP], Luis Rivera[SUP] 6 [/SUP], Damien Friel[SUP] 7 [/SUP], Wenji Pu[SUP] 1 [/SUP], Valerie Vantomme[SUP] 2 [/SUP], Ghassan Dbaibo[SUP] 8 [/SUP], Bruce L Innis[SUP] 9 [/SUP], Anne Schuind[SUP] 1 [/SUP], Khalequ Zaman[SUP] 10 [/SUP], Jerome Wilson[SUP] 1 [/SUP]
Affiliations
- PMID: 35083365
- PMCID: PMC8786493
- DOI: 10.1093/ofid/ofab477
Abstract
Background: Data 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.
Methods: The 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.
Results: Prentice 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.
Conclusions: The 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 registration: NCT01439360.
Keywords: HI antibodies; children; correlate of protection; influenza.