TY - JOUR
T1 - On the use of hemagglutination-inhibition for influenza surveillance
T2 - Surveillance data are predictive of influenza vaccine effectiveness
AU - Ndifon, Wilfred
AU - Dushoff, Jonathan
AU - Levin, Simon Asher
N1 - Funding Information:
W.N. acknowledges support from a Burroughs-Wellcome Graduate Fellowship, while J.D. acknowledges support from the Natural Sciences and Engineering Research Council of Canada. We are also pleased to acknowledge support from the Defense Advanced Research Projects Agency (DARPA), grant HR0011-05-1-0057. We are grateful to two anonymous reviewers for their very helpful comments on this manuscript.
PY - 2009/4/21
Y1 - 2009/4/21
N2 - The hemagglutination-inhibition (HI) assay is the main tool used by epidemiologists to quantify antigenic differences between circulating influenza virus strains, with the goal of selecting suitable vaccine strains. However, such quantitative measures of antigenic difference were recently shown to have poor predictive accuracy with respect to influenza vaccine effectiveness (VE) in healthy adults. Here, we re-examine those results using a more rigorous criterion for predictive accuracy - considering only cases when the vaccine (V) and dominant (D) circulating strains are antigenically different - and greater numbers of HI titers. We find that the Archetti-Horsfall measure of antigenic difference, which is based on both the normalized HI titer (NHI) of D relative to antisera raised against V and the NHI of V relative to D, predicts VE very well (R2 = 0.62, p = 4.1 × 10-3). In contrast, the predictive accuracies of the NHI of D relative to V alone (R2 = 0.01), and two other measures of antigenic difference based on the amino acid sequence of influenza virus hemagglutinin (R2 = 0.03 for both measures) are relatively poor. Furthermore, while VE in the elderly is generally high in cases when D and V are antigenically identical (VE = 35%, S.E. = 5%), in other cases VE appears to increase with the antigenic difference between D and V (R2 = 0.90, p = 2.5 × 10-5). This paradoxical observation could reflect the confounding effects of prior immunity on estimates of VE in the elderly. Together, our results underscore the need for consistently accurate selection of suitable vaccine strains. We suggest directions for further studies aimed at improving vaccine-strain selection and present a large collection of HI titers that will be useful to such studies.
AB - The hemagglutination-inhibition (HI) assay is the main tool used by epidemiologists to quantify antigenic differences between circulating influenza virus strains, with the goal of selecting suitable vaccine strains. However, such quantitative measures of antigenic difference were recently shown to have poor predictive accuracy with respect to influenza vaccine effectiveness (VE) in healthy adults. Here, we re-examine those results using a more rigorous criterion for predictive accuracy - considering only cases when the vaccine (V) and dominant (D) circulating strains are antigenically different - and greater numbers of HI titers. We find that the Archetti-Horsfall measure of antigenic difference, which is based on both the normalized HI titer (NHI) of D relative to antisera raised against V and the NHI of V relative to D, predicts VE very well (R2 = 0.62, p = 4.1 × 10-3). In contrast, the predictive accuracies of the NHI of D relative to V alone (R2 = 0.01), and two other measures of antigenic difference based on the amino acid sequence of influenza virus hemagglutinin (R2 = 0.03 for both measures) are relatively poor. Furthermore, while VE in the elderly is generally high in cases when D and V are antigenically identical (VE = 35%, S.E. = 5%), in other cases VE appears to increase with the antigenic difference between D and V (R2 = 0.90, p = 2.5 × 10-5). This paradoxical observation could reflect the confounding effects of prior immunity on estimates of VE in the elderly. Together, our results underscore the need for consistently accurate selection of suitable vaccine strains. We suggest directions for further studies aimed at improving vaccine-strain selection and present a large collection of HI titers that will be useful to such studies.
KW - Antigenic data
KW - Antigenic distance hypothesis
KW - Archetti-Horsfall measure
KW - Vaccine-strain selection
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U2 - 10.1016/j.vaccine.2009.02.047
DO - 10.1016/j.vaccine.2009.02.047
M3 - Article
C2 - 19368786
AN - SCOPUS:62749138195
SN - 0264-410X
VL - 27
SP - 2447
EP - 2452
JO - Vaccine
JF - Vaccine
IS - 18
ER -