Relationship between haemagglutination-inhibiting antibody titres and clinical protection against influenza: development and application of a bayesian random-effects model

Abstract

BackgroundAntibodies directed against haemagglutinin, measured by the haemagglutination inhibition (HI) assay are essential to protective immunity against influenza infection. An HI titre of 1:40 is generally accepted to correspond to a 50% reduction in the risk of contracting influenza in a susceptible population, but limited attempts have been made to further quantify the association between HI titre and protective efficacy.MethodsWe present a model, using a meta-analytical approach, that estimates the level of clinical protection against influenza at any HI titre level. Source data were derived from a systematic literature review that identified 15 studies, representing a total of 5899 adult subjects and 1304 influenza cases with interval-censored information on HI titre. The parameters of the relationship between HI titre and clinical protection were estimated using Bayesian inference with a consideration of random effects and censorship in the available information.ResultsA significant and positive relationship between HI titre and clinical protection against influenza was observed in all tested models. This relationship was found to be similar irrespective of the type of viral strain (A or B) and the vaccination status of the individuals.ConclusionAlthough limitations in the data used should not be overlooked, the relationship derived in this analysis provides a means to predict the efficacy of inactivated influenza vaccines when only immunogenicity data are available. This relationship can also be useful for comparing the efficacy of different influenza vaccines based on their immunological profile.

Safety, immunogenicity, and tolerability of three influenza vaccines in older adults

“…Titers ≥ 160 were also seen more often after ADV than TIV and are reportedly more predictive of protection than the standard threshold. [27][28][29] While statistically significant, the differences in seroprotection rates and GMT ratios after ADV or TIV were of modest magnitude. Baseline titers of the annually immunized study participants were moderately high, which might have reduced potential differences in responses to both vaccines.…”

Immunogenicity of intramuscular MF59-adjuvanted and intradermal administered influenza enhanced vaccines in subjects aged over 60: A literature review

“…32 HI titers were considered according to EMA immunogenicity criteria 10 although there are some disagreements on the identification of a single threshold (HI titer 40) for defining protection. 34 The HI assay has some limitations in terms of sensitivity and specificity 32 and recent studies show that serum HI antibody titers may not be associated with the development of influenza. Moreover, because of the importance and difficulties of evaluating efficacy and effectiveness of vaccine administration, there is the need for studies to provide estimates of vaccine effectiveness during each season and to collect protection data from laboratory-confirmed cases (PCR or virus isolation).…”

“…32 However there is the need to better define correlates of protection and there are some perplexities on the identification of a single threshold HI titer for defining protection. 34 The SRH is a different test that can be used to detect antibodies to HA, but is less frequently reported. 33 The test is based on immunodiffusion of antibodies against HA in agarose gel containing influenza virus bound to red blood cells and complement.…”

Reply: Letter to the Editor, Cochrane Rearranged

“…We have also found that the association between protection and a specific antibody cut-off point is poor [2]. Pre-season HI antibody and protection are strongly connected in a curvilinear manner: the higher the antibody titre, the lower the chance of infection [3]. Estimation of protection from antibody titres is possible if the entire protection curve (rather than a single cut-off point) is considered.…”