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

• Published in: Cell reports. Medicine 2020-11, Vol.1 (8), p.100130-100130, Article 100130
• Main Authors: Aydillo, Teresa, Escalera, Alba, Strohmeier, Shirin, Aslam, Sadaf, Sanchez-Cespedes, Javier, Ayllon, Juan, Roca-Oporto, Cristina, Perez-Romero, Pilar, Montejo, Miguel, Gavalda, Joan, Munoz, Patricia, Lopez-Medrano, Francisco, Carratala, Jordi, Krammer, Florian, García-Sastre, Adolfo, Cordero, Elisa
• Format: Article
• Language: English
• Subjects: Adult; Aged; Animals; Antibodies, Neutralizing - immunology; Antibodies, Viral - immunology; Cell Line; correlates of protection; Cross Protection - immunology; Cross Reactions - immunology; Dogs; Female; Hemagglutination Inhibition Tests - methods; Hemagglutinins - immunology; Humans; Influenza A Virus, H1N1 Subtype - immunology; influenza antibodies; Influenza, Human - immunology; Lower Urinary Tract Symptoms - immunology; Lower Urinary Tract Symptoms - virology; Madin Darby Canine Kidney Cells; Male; Middle Aged; Neutralization Tests - methods; transplant patients; viral pneumonia; Young Adult
• ISSN: 2666-3791; 2666-3791
• DOI: 10.1016/j.xcrm.2020.100130

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. [Display omitted] Solid organ transplant recipients (SOTRs) had low levels of HAI antibodies at baselineSOTRs have high levels of pre-existing, broadly cross-reactive anti-HA stalk antibodiesAnti-HA stalk antibodies correlate with lack of lower respiratory symptoms in SOTRsPresence of lower respiratory symptoms is associated with influenza pneumonia Aydillo et al. identify lower respiratory symptoms (LRSs) as a predictor of influenza pneumonia in a cohort of transplant recipients. When pre-existing immunity was characterized, the levels of anti-HA stalk antibodies correlated independently with protection from lower respiratory infection.