Pre-existing Hemagglutinin Stalk Antibodies Correlate with Protection of Lower Respiratory Symptoms in Flu-Infected Transplant Patients

Cell Rep Med. 2020 Nov 3;1(8):100130. doi: 10.1016/j.xcrm.2020.100130. eCollection 2020 Nov 17.

Abstract

Hemagglutination-inhibitory antibodies are usually highly strain specific with little effect on infection with drifted or shifted strains. The significance of broadly cross-reactive non-HAI anti-influenza antibodies against conserved domains of virus glycoproteins, such as the hemagglutinin (HA) stalk, is of great interest. We characterize a cohort of 40 H1N1pmd09 influenza-infected patients and identify lower respiratory symptoms (LRSs) as a predictor for development of pneumonia. A binomial logistic regression of log10 pre-existing antibody values shows that the probability of LRS occurrence decreased with increased anti-HA full-length and stalk antibody ELISA titers. However, a multilevel logistic regression model adjusted by other potential serocorrelates demonstrates that only antibodies directed against the stalk of HA correlate with protection from lower respiratory infection, limiting disease progression. Our predictive model indicates that a threshold of protective immunity based on broadly cross-reactive HA stalk antibodies could be feasible.

Keywords: correlates of protection; influenza antibodies; transplant patients; viral pneumonia.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Animals
  • Antibodies, Neutralizing / immunology*
  • Antibodies, Viral / immunology*
  • Cell Line
  • Cross Protection / immunology
  • Cross Reactions / immunology
  • Dogs
  • Female
  • Hemagglutination Inhibition Tests / methods
  • Hemagglutinins / immunology*
  • Humans
  • Influenza A Virus, H1N1 Subtype / immunology
  • Influenza, Human / immunology*
  • Lower Urinary Tract Symptoms / immunology*
  • Lower Urinary Tract Symptoms / virology
  • Madin Darby Canine Kidney Cells
  • Male
  • Middle Aged
  • Neutralization Tests / methods
  • Young Adult

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Hemagglutinins