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
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Oxford University Press
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. © 2021 The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.
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Children, Correlate of protection, Hi antibodies, Influenza, Chickenpox vaccine, Hemagglutination inhibiting antibody, Influenza vaccine, Pneumococcus vaccine, Antibody response, Antibody titer, Article, Child, Clinical outcome, Controlled study, Drug efficacy, Enzyme linked immunosorbent assay, Exploratory research, Gene expression, Human, Immune response, Immunization, Immunogenicity, Influenza a (h1n1), Influenza a (h3n2), Mean corpuscular hemoglobin, Nonhuman, Nose smear, Preschool child, Probability, Randomized controlled trial, Respiratory syncytial virus infection, Reverse transcription polymerase chain reaction, Rhinorrhea, Risk factor, Seasonal variation, Vaccination