TY - JOUR
T1 - Pre-existing Hemagglutinin Stalk Antibodies Correlate with Protection of Lower Respiratory Symptoms in Flu-Infected Transplant Patients
AU - Aydillo, Teresa
AU - Escalera, Alba
AU - Strohmeier, Shirin
AU - Aslam, Sadaf
AU - Sanchez-Cespedes, Javier
AU - Ayllon, Juan
AU - Roca-Oporto, Cristina
AU - Perez-Romero, Pilar
AU - Montejo, Miguel
AU - Gavalda, Joan
AU - Munoz, Patricia
AU - Lopez-Medrano, Francisco
AU - Carratala, Jordi
AU - Krammer, Florian
AU - García-Sastre, Adolfo
AU - Cordero, Elisa
N1 - Funding Information:
This work was supported by the Programa de Investigación sobre gripe A/H1N1, Instituto de Salud Carlos III, Ministerio. de Ciencia e Innovación (GR09/0041); the Ministerio de Ciencia e Innovación, Instituto de Salud Carlos III, co-financed by the European Development Regional Fund “A way to Achieve Europe” ERDF; the Spanish Network for Research in Infectious Diseases (REIPI RD06/0008 to E.C.); NIAID grants P01AI097092 and U19AI135972; CRIP (Center for Research on Influenza Pathogenesis), an NIAID-funded Center of Excellence on Influenza Research and Surveillance (CEIRS; contract HHSN272201400008C); and SEM-CIVIC, an NIAID-funded Collaborative Influenza Vaccine Innovation Center (contract 75N93019C00051 to A.G.-S. and F.K.). T.A. E.C. and A.G.-S. conceived and designed the study. T.A. collected samples and data, performed experiments, analyzed data, and wrote the report. A.E. performed experiments. S.S. S.A. J.A. and F.K. provided reagents, methods, and expertise. P.P.-R. C.R.-O. M.M. J.G. P.M. F.L.-M. J.S.-C. and J.C. collected samples and data. T.A. E.C. and A.G.-S. supervised the study. All authors reviewed and edited the paper. A.G.-S. is an inventor of patents owned by the Icahn School of Medicine at Mount Sinai in the field of influenza virus vaccines. The A.G.-S. lab has received research funds from Avimex, GSK, and 7Hills to investigate novel influenza virus vaccines. F.K. is a named inventor of technology in the field of human influenza vaccines and a named co-inventor on patents to develop chimeric HA technology to develop a universal influenza vaccine.
Funding Information:
This work was supported by the Programa de Investigación sobre gripe A/H1N1, Instituto de Salud Carlos III, Ministerio. de Ciencia e Innovación ( GR09/0041 ); the Ministerio de Ciencia e Innovación, Instituto de Salud Carlos III , co-financed by the European Development Regional Fund “A way to Achieve Europe” ERDF ; the Spanish Network for Research in Infectious Diseases ( REIPI RD06/0008 to E.C.); NIAID grants P01AI097092 and U19AI135972 ; CRIP (Center for Research on Influenza Pathogenesis), an NIAID -funded Center of Excellence on Influenza Research and Surveillance (CEIRS; contract HHSN272201400008C ); and SEM-CIVIC , an NIAID -funded Collaborative Influenza Vaccine Innovation Center (contract 75N93019C00051 to A.G.-S. and F.K.).
Publisher Copyright:
© 2020 The Authors
PY - 2020/11/17
Y1 - 2020/11/17
N2 - 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.
AB - 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.
KW - correlates of protection
KW - influenza antibodies
KW - transplant patients
KW - viral pneumonia
UR - http://www.scopus.com/inward/record.url?scp=85096622891&partnerID=8YFLogxK
U2 - 10.1016/j.xcrm.2020.100130
DO - 10.1016/j.xcrm.2020.100130
M3 - Article
C2 - 33294855
AN - SCOPUS:85096622891
SN - 2666-3791
VL - 1
JO - Cell Reports Medicine
JF - Cell Reports Medicine
IS - 8
M1 - 100130
ER -