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J Clin Microbiol Comparability of Antibody Titers Determined by Hemagglutination Inhibition and Microneutralization Assays Against Seasonal Influenza

tetano

Editor, Senior Moderator
J Clin Microbiol


. 2020 Jun 3;JCM.00750-20.
doi: 10.1128/JCM.00750-20. Online ahead of print.
Comparability of Antibody Titers Determined by Hemagglutination Inhibition and Microneutralization Assays Against Seasonal Influenza Strains


Marten Heeringa[SUP] 1 [/SUP], Brett Leav[SUP] 2 [/SUP], Igor Smolenov[SUP] 2 [/SUP], Giuseppe Palladino[SUP] 2 [/SUP], Leah Isakov[SUP] 2 [/SUP], Vincent Matassa[SUP] 3 [/SUP]



Affiliations
Free article

Abstract

We compared hemagglutination inhibition (HI) and microneutralization (MN) assays pre- and post-vaccination antibody titers against A/H1N1, A/H3N2, and B influenza strains using data from two vaccine trials: Study 1 with a cell-grown trivalent influenza vaccine (TIVc) using cell-grown target virus in both assays and Study 2 with an egg-grown adjuvanted quadrivalent influenza vaccine (aQIVe) using egg-grown target virus. The relationships between HI- and MN-derived log-transformed titers were examined using different statistical techniques. Deming regression analyses showed point estimates for slopes generally close to 1 across studies and strains. The slope of regression was closest to 1 for A/H3N2 strain when either cell- or egg-grown viral target virus was used. Bland-Altman plots indicated a very small percentage of results outside 2 and 3 standard deviations. The magnitude and direction of differences between titers in the two assays varied by study and strain. Mean differences favored the MN assay for A/H1N1 and B strains in Study 1, whereas HI resulted in higher titers compared to MN against the A/H3N2 strain. In Study 2, mean differences favored the MN assay for A/H3N2 and B strains. Overall the direction and magnitude of mean differences were similar between the two vaccines. The concordance correlation coefficients ranged from 0.74 (A/H1N1 strain, Study 1) to 0.97 (A/H3N2 strain, Study 1). The comparative analysis demonstrates an overall strong positive correlation between HI and MN assays. These data support the use of the MN assay to quantify the immune response of influenza vaccines in clinical studies, particularly for A/H3N2 strain.
 
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