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. 2015 May 14;2(2):ofv067.
doi: 10.1093/ofid/ofv067. eCollection 2015 Apr.

Hemagglutination Inhibition Antibody Titers as a Correlate of Protection Against Seasonal A/H3N2 Influenza Disease

Anne Benoit  1 , Jiri Beran  2 , Jeanne-Marie Devaster  3 , Meral Esen  4 , Odile Launay  5 , Geert Leroux-Roels  6 , Janet E McElhaney  7 , Lidia Oostvogels  3 , Gerrit A van Essen  8 , Manjusha Gaglani  9 , Lisa A Jackson  10 , Timo Vesikari  11 , Catherine Legrand  1 , Fabian Tibaldi  3 , Bruce L Innis  12 , Walthère Dewé  3
Affiliations

Hemagglutination Inhibition Antibody Titers as a Correlate of Protection Against Seasonal A/H3N2 Influenza Disease

Anne Benoit et al. Open Forum Infect Dis. .

Abstract

Background. To investigate the relationship between hemagglutinin-inhibition (HI) antibody levels to the risk of influenza disease, we conducted a correlate of protection analysis using pooled data from previously published randomized trials. Methods. Data on the occurrence of laboratory-confirmed influenza and HI levels pre- and postvaccination were analyzed from 4 datasets: 3 datasets included subjects aged <65 years who received inactivated trivalent influenza vaccine (TIV) or placebo, and 1 dataset included subjects aged ≥65 years who received AS03-adjuvanted TIV (AS03-TIV) or TIV. A logistic model was used to evaluate the relationship between the postvaccination titer of A/H3N2 HI antibodies and occurrence of A/H3N2 disease. We then built a receiver-operating characteristic curve to identify a potential cutoff titer between protection and no protection. Results. The baseline odds ratio of A/H3N2 disease was higher for subjects aged ≥65 years than <65 years and higher in seasons of strong epidemic intensity than moderate or low intensity. Including age and epidemic intensity as covariates, a 4-fold increase in titer was associated with a 2-fold decrease in the risk of A/H3N2 disease. Conclusions. The modeling exercise confirmed a relationship between A/H3N2 disease and HI responses, but it did not allow an evaluation of the predictive power of the HI response.

Keywords: A/H3N2; influenza; modeling; serologic correlates; vaccine.

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Figures

Figure 1.
Figure 1.
Overview of analysis population (descriptive analysis). Abbreviation: TIV, inactivated trivalent influenza vaccine.
Figure 2.
Figure 2.
Number of subjects in each titer category and number of A/H3N2 cases (A) and proportion of subjects in each titer category with laboratory-confirmed A/H3N2 infection (B) (descriptive analysis).
Figure 3.
Figure 3.
A/H3N2 HI antibody titer and estimated risk of A/H3N2 influenza disease in subjects aged ≥65 years in an epidemic of low to moderate intensity (A) or high intensity (B), and in subjects aged <65 years in an epidemic of low to moderate intensity (C) or high intensity (D). Dots represent the observed proportions of cases and shading shows 95% confidence interval (logistic regression). Abbreviation: HI, hemagglutination inhibition
See this image and copyright information in PMC

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