Influenza Hemagglutination-inhibition Antibody Titer as a Mediator of Vaccine-induced Protection for Influenza B

Clin Infect Dis. 2019 May 2;68(10):1713-1717. doi: 10.1093/cid/ciy759.

Abstract

Background: The hemagglutination inhibition (HAI) assay is an established correlate of protection for the inactivated influenza vaccine. However, the proportion of vaccine-induced protection that is mediated by the post-vaccination HAI titer has not been assessed.

Methods: We used data from a randomized, placebo-controlled trial of a split-virion inactivated influenza vaccine in children aged 6-17 years. Sera were collected before and 30 days after receipt of vaccination or placebo and tested by the HAI assay against B/Brisbane/60/2008-like (B/Victoria lineage). We fitted Cox proportional hazards models to the time to laboratory-confirmed influenza B. We used causal mediation analysis to estimate the proportion of the total effect of vaccination that was mediated by higher HAI titers.

Results: We estimated that vaccine efficacy against confirmed B/Victoria infection was 68% (95% confidence interval, 33%, 88%), and post-vaccination HAI titers explained 57% of the effect of vaccination on protection.

Conclusions: The majority of the effect of inactivated influenza vaccination in children is mediated by the increased HAI titer after vaccination; however, other components of the immune response to vaccination may also play a role in protection and should be further explored. Causal mediation analysis provides a framework to quantify the role of various mediators of protection.

Keywords: correlate of protection; hemagglutination inhibition; influenza; vaccination.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antibodies, Viral / blood*
  • Child
  • Hemagglutination Inhibition Tests
  • Humans
  • Influenza B virus
  • Influenza Vaccines / administration & dosage
  • Influenza Vaccines / immunology*
  • Influenza, Human / immunology*
  • Influenza, Human / prevention & control
  • Proportional Hazards Models
  • Randomized Controlled Trials as Topic
  • Vaccine Potency*
  • Vaccines, Inactivated / administration & dosage
  • Vaccines, Inactivated / immunology

Substances

  • Antibodies, Viral
  • Influenza Vaccines
  • Vaccines, Inactivated