title: Broadly cross-reactive antibodies dominate the human B cell response against 2009 pandemic H1N1 influenza virus infection.
abstract: The 2009 pandemic H1N1 influenza pandemic demonstrated the global health threat of reassortant influenza strains. Herein, we report a detailed analysis of plasmablast and monoclonal antibody responses induced by pandemic H1N1 infection in humans. Unlike antibodies elicited by annual influenza vaccinations, most neutralizing antibodies induced by pandemic H1N1 infection were broadly cross-reactive against epitopes in the hemagglutinin (HA) stalk and head domain of multiple influenza strains. The antibodies were from cells that had undergone extensive affinity maturation. Based on these observations, we postulate that the plasmablasts producing these broadly neutralizing antibodies were predominantly derived from activated memory B cells specific for epitopes conserved in several influenza strains. Consequently, most neutralizing antibodies were broadly reactive against divergent H1N1 and H5N1 influenza strains. This suggests that a pan-influenza vaccine may be possible, given the right immunogen. Antibodies generated potently protected and rescued mice from lethal challenge with pandemic H1N1 or antigenically distinct influenza strains, making them excellent therapeutic candidates.
authors.affiliation: Emory Vaccine Center, School of Medicine, Emory University, Atlanta, GA 30322, USA.
authors.forename: Jens
authors.initials: J
authors.lastname: Wrammert
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Koutsonanos
authors.forename: Gui-Mei
authors.initials: GM
authors.lastname: Li
authors.forename: Srilatha
authors.initials: S
authors.lastname: Edupuganti
authors.forename: Jianhua
authors.initials: J
authors.lastname: Sui
authors.forename: Michael
authors.initials: M
authors.lastname: Morrissey
authors.forename: Megan
authors.initials: M
authors.lastname: McCausland
authors.forename: Ioanna
authors.initials: I
authors.lastname: Skountzou
authors.forename: Mady
authors.initials: M
authors.lastname: Hornig
authors.forename: W Ian
authors.initials: WI
authors.lastname: Lipkin
authors.forename: Aneesh
authors.initials: A
authors.lastname: Mehta
authors.forename: Behzad
authors.initials: B
authors.lastname: Razavi
authors.forename: Carlos
authors.initials: C
authors.lastname: Del Rio
authors.forename: Nai-Ying
authors.initials: NY
authors.lastname: Zheng
authors.forename: Jane-Hwei
authors.initials: JH
authors.lastname: Lee
authors.forename: Min
authors.initials: M
authors.lastname: Huang
authors.forename: Zahida
authors.initials: Z
authors.lastname: Ali
authors.forename: Kaval
authors.initials: K
authors.lastname: Kaur
authors.forename: Sarah
authors.initials: S
authors.lastname: Andrews
authors.forename: Rama Rao
authors.initials: RR
authors.lastname: Amara
authors.forename: Youliang
authors.initials: Y
authors.lastname: Wang
authors.forename: Suman Ranjan
authors.initials: SR
authors.lastname: Das
authors.forename: Christopher David
authors.initials: CD
authors.lastname: O'Donnell
authors.forename: Jon W
authors.initials: JW
authors.lastname: Yewdell
authors.forename: Kanta
authors.initials: K
authors.lastname: Subbarao
authors.forename: Wayne A
authors.initials: WA
authors.lastname: Marasco
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Mulligan
authors.forename: Richard
authors.initials: R
authors.lastname: Compans
authors.forename: Rafi
authors.initials: R
authors.lastname: Ahmed
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Wilson
mesh_terms: D000328:Adult; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D003429:Cross Reactions; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D005260:Female; D006801:Humans; D007156:Immunologic Memory; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D018985:Epitopes, B-Lymphocyte