title: Association between Hemagglutinin Stem-Reactive Antibodies and Influenza A/H1N1 Virus Infection during the 2009 Pandemic.
abstract: The discovery of influenza virus broadly neutralizing (BrN) antibodies prompted efforts to develop universal vaccines. Influenza virus stem-reactive (SR) broadly neutralizing antibodies have been detected by screening antibody phage display libraries. However, studies of SR BrN antibodies in human serum, and their association with natural infection, are limited. To address this, pre- and postpandemic sera from a prospective community cohort study in Vietnam were assessed for antibodies that inhibit SR BrN monoclonal antibody (MAb) (C179) binding to H1N1 pandemic 2009 virus (H1N1pdm09). Of 270 households, 33 with at least one confirmed H1N1pdm09 illness or at least two seroconverters were included. The included households comprised 71 infected and 41 noninfected participants. Sera were tested as 2-fold dilutions between 1:5 and 1:40. Fifty percent C179 inhibition (IC50) titers did not exceed 10, although both IC50 titers and percent C179 inhibition by sera diluted 1:5 or 1:10 correlated with hemagglutination inhibition (HI) and microneutralization (MN) titers (all P < 0.001). Thirteen (12%) participants had detectable prepandemic IC50 titers, but only one reached a titer of 10. This proportion increased to 44% after the pandemic, when 39 participants had a titer of 10, and 67% of infected compared to 44% of noninfected had detectable IC50 titers (P < 0.001). The low levels of SR antibodies in prepandemic sera were not associated with subsequent H1N1pdm09 infection (P = 0.241), and the higher levels induced by H1N1pdm09 infection returned to prepandemic levels within 2 years. The findings indicate that natural infection induces only low titers of SR antibodies that are not sustained.
  
  
  
  Universal influenza vaccines could have substantial health and economic benefits. The focus of universal vaccine research has been to induce antibodies that prevent infection by diverse influenza virus strains. These so-called broadly neutralizing antibodies are readily detected in mice and ferrets after infection with a series of distinct influenza virus strains. The 2009 H1N1 pandemic provided an opportunity to investigate whether infection with a novel strain induced broadly neutralizing antibodies in humans. We found that broadly neutralizing antibodies were induced, but levels were low and poorly maintained. This could represent an obstacle for universal vaccine development and warrants further investigation.
authors.affiliation: Oxford University Clinical Research Unit and Wellcome Trust Major Overseas Programme, Hanoi, Vietnam.
authors.forename: Le Nguyen Minh
authors.initials: LNM
authors.lastname: Hoa
authors.affiliation: National Institute of Hygiene and Epidemiology, Hanoi, Vietnam.
authors.forename: Le Quynh
authors.initials: LQ
authors.lastname: Mai
authors.affiliation: Oxford University Clinical Research Unit and Wellcome Trust Major Overseas Programme, Hanoi, Vietnam.|Center for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: Juliet E
authors.initials: JE
authors.lastname: Bryant
authors.affiliation: National Institute of Hygiene and Epidemiology, Hanoi, Vietnam.
authors.forename: Pham Quang
authors.initials: PQ
authors.lastname: Thai
authors.affiliation: National Institute of Hygiene and Epidemiology, Hanoi, Vietnam.
authors.forename: Nguyen Le Khanh
authors.initials: NLK
authors.lastname: Hang
authors.affiliation: National Institute of Hygiene and Epidemiology, Hanoi, Vietnam.
authors.forename: Nguyen Thi Thu
authors.initials: NTT
authors.lastname: Yen
authors.affiliation: National Institute of Hygiene and Epidemiology, Hanoi, Vietnam.
authors.forename: Tran Nhu
authors.initials: TN
authors.lastname: Duong
authors.affiliation: Ha Nam Centre for Preventive Medicine, Ha Nam, Vietnam.
authors.forename: Dang Dinh
authors.initials: DD
authors.lastname: Thoang
authors.affiliation: Oxford University Clinical Research Unit and Wellcome Trust Major Overseas Programme, Hanoi, Vietnam.|Center for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: Peter
authors.initials: P
authors.lastname: Horby
authors.affiliation: Oxford University Clinical Research Unit and Wellcome Trust Major Overseas Programme, Hanoi, Vietnam.|Center for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom.|Department of Medical Microbiology, Radboudumc, Nijmegen, Netherlands.
authors.forename: Heiman F L
authors.initials: HFL
authors.lastname: Werheim
authors.affiliation: Oxford University Clinical Research Unit and Wellcome Trust Major Overseas Programme, Hanoi, Vietnam annette.fox@unimelb.edu.au.|The University of Melbourne, Peter Doherty Institute for Infection and Immunity, Department of Microbiology and Immunology, Parkville, Victoria, Australia.
authors.forename: Annette
authors.identifier: http://orcid.org/0000-0002-0565-7146
authors.initials: A
authors.lastname: Fox
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D057134:Antibodies, Neutralizing / Q000097:blood*; D000914:Antibodies, Viral / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005289:Ferrets; D006385:Hemagglutination Inhibition Tests; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007251:Influenza, Human / Q000097:blood* / Q000453:epidemiology / Q000276:immunology / Q000821:virology; D008297:Male; D051379:Mice; D008875:Middle Aged; D058873:Pandemics; D011446:Prospective Studies; D013997:Time Factors; D014744:Vietnam / Q000453:epidemiology; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus