title: Non-neutralizing antibodies induced by seasonal influenza vaccine prevent, not exacerbate A(H1N1)pdm09 disease.
abstract: The association of seasonal trivalent influenza vaccine (TIV) with increased infection by 2009 pandemic H1N1 (A(H1N1)pdm09) virus, initially observed in Canada, has elicited numerous investigations on the possibility of vaccine-associated enhanced disease, but the potential mechanisms remain largely unresolved. Here, we investigated if prior immunization with TIV enhanced disease upon A(H1N1)pdm09 infection in mice. We found that A(H1N1)pdm09 infection in TIV-immunized mice did not enhance the disease, as measured by morbidity and mortality. Instead, TIV-immunized mice cleared A(H1N1)pdm09 virus and recovered at an accelerated rate compared to control mice. Prior TIV immunization was associated with potent inflammatory mediators and virus-specific CD8 T cell activation, but efficient immune regulation, partially mediated by IL-10R-signaling, prevented enhanced disease. Furthermore, in contrast to suggested pathological roles, pre-existing non-neutralizing antibodies (NNAbs) were not associated with enhanced virus replication, but rather with promoted antigen presentation through FcR-bearing cells that led to potent activation of virus-specific CD8 T cells. These findings provide new insights into interactions between pre-existing immunity and pandemic viruses.
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Rd, Atlanta, GA 30329, USA.
authors.forename: Jin Hyang
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Rd, Atlanta, GA 30329, USA.
authors.forename: Adrian J
authors.initials: AJ
authors.lastname: Reber
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Rd, Atlanta, GA 30329, USA.
authors.forename: Amrita
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Rd, Atlanta, GA 30329, USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Ramos
authors.affiliation: Department of Pathology and Laboratory Medicine, School of Medicine, Emory University, 1364 Clifton Rd, N.E. Atlanta, GA 30322, USA.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Sica
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Rd, Atlanta, GA 30329, USA.
authors.forename: Nedzad
authors.initials: N
authors.lastname: Music
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Rd, Atlanta, GA 30329, USA.
authors.forename: Zhu
authors.initials: Z
authors.lastname: Guo
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Rd, Atlanta, GA 30329, USA.|Batelle Memorial Institute, Atlanta, GA 30322, USA.
authors.forename: Margarita
authors.initials: M
authors.lastname: Mishina
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Rd, Atlanta, GA 30329, USA.
authors.forename: James
authors.initials: J
authors.lastname: Stevens
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Rd, Atlanta, GA 30329, USA.
authors.forename: Ian A
authors.initials: IA
authors.lastname: York
authors.affiliation: Department of Microbiology and Immunology, Emory Vaccine Center, Yerkes National Primate Center, Emory University, 954 Gatewood Rd, Atlanta, GA, USA.
authors.forename: Joshy
authors.initials: J
authors.lastname: Jacob
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Rd, Atlanta, GA 30329, USA.
authors.forename: Suryaprakash
authors.initials: S
authors.lastname: Sambhara
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D053701:Receptors, Interleukin-10 / Q000276:immunology; D012621:Seasons; D015398:Signal Transduction / Q000276:immunology; D014611:Vaccination
chemical_list: D000914:Antibodies, Viral; D007252:Influenza Vaccines; D053701:Receptors, Interleukin-10