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The evaluation of hemagglutination-inhibition antibody titer as a mediator of vaccine-induced protection against laboratory-confirmed influenza infections
Proposal
5460
Title of Proposed Research
The evaluation of hemagglutination-inhibition antibody titer as a mediator of vaccine-induced protection against laboratory-confirmed influenza infections
Lead Researcher
Prof Benjamin J Cowling
Affiliation
School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong.
Funding Source
none
Potential Conflicts of Interest
Prof. Cowling has received research funding from Sanofi Pasteur for a study of influenza vaccination effectiveness in 2013-16. Prof. Cowling has received research funding from Sanofi Pasteur for a study of influenza vaccination effectiveness in 2013-16.
Data Sharing Agreement Date
16 July 2018
Lay Summary
Background:Inactivated influenza vaccines (IIV) are the most commonly administered influenza vaccines globally. Due to constant mutations in circulating influenza viruses, influenza vaccines need to be updated annually to include strains that are expected to circulate in the upcoming influenza season. The hemagglutinin inhibition (HI) antibody response is an established surrogate endpoint for IIVs that reasonably predicts clinical benefit, but the HI response only reflects part of the total immune response to vaccination.Aim:To examine the role of HI antibodies in vaccine-induced protection against confirmed influenza infections within a causal analysis framework, specifically the fraction of vaccine-associated protection that is mediated by the increase in HI antibody titers.Design and subjects:We will re-analyze data collected for 3 completed clinical trials conducted between years 2008 and 2014 to assess the efficacy of two quadrivalent and one trivalent influenza vaccines in preventing laboratory-confirmed influenza in children and adults above the age of 65 years.Main outcome measures:The total effect of vaccination on protection against confirmed influenza infections and the proportion of protective effect by vaccination that is mediated by post-vaccination HI titers.Analysis:Proportional hazards models will be used to estimate the total effect of vaccination on protection against confirmed influenza and the direct effect of vaccination on protection that is not mediated by HI titers. Causal mediation analysis will then be used to infer the fraction of vaccine efficacy that is mediated by the effect of vaccination on HI titers.
Study Data Provided
[{ "PostingID": 214, "Title": "GSK-106372", "Description": "Observer-blind superior efficacy trial with GlaxoSmithKline Biologicals' influenza vaccine GSK2186877A in elderly subjects" },{ "PostingID": 1609, "Title": "GSK-114541", "Description": "Efficacy study of GSK Biologicals’ quadrivalent influenza vaccine, GSK2282512A, (FLU Q-QIV) when administered in children" },{ "PostingID": 5116, "Title": "GSK-115345", "Description": "An efficacy study of GSK Biologicals’ quadrivalent influenza vaccine GSK2321138A (FLU D-QIV) when administered in children" }]
Statistical Analysis Plan
For our mediation analysis, a proportional hazards model will be used to estimate the “total” effect of vaccination on protection. The hazard ratio of vaccination represents the total effect, and 1 minus the hazard ratio multiplied by 100% represents the vaccine efficacy. Another proportional hazards model, weighted by post-vaccination titer and adjusted for age and receipt of IIV or placebo, will then be used to estimate the “direct” effect of vaccination of protection. Finally, the indirect effect will be obtained as the ratio of the total effect and the direct effect. The associations between influenza vaccination, pre-vaccination HI antibody titers, post-vaccination HI antibody titers, and protection against confirmed influenza will be assessed with multivariable linear and logistic regression analyses.The uncertainty in proportional hazards model estimates will be estimated by bootstrapping.
Publication Citation
Wey Wen Lim, Shuo Feng, Sook-San Wong, Sheena G Sullivan, Benjamin J Cowling, Hemagglutination Inhibition Antibody Titers as Mediators of Influenza Vaccine Efficacy Against Symptomatic Influenza A(H1N1), A(H3N2), and B/Victoria Virus Infections, The Journal of Infectious Diseases, 2024
DOI:
https://doi.org/10.1093/infdis/jiae122
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