Non-neutralizing antibodies induced by seasonal influenza vaccine prevent, not exacerbate A(H1N1)pdm09 disease

• Type of Material: Article
• Authors: Jin Hyang Kim, Centers for Disease Control and Prevention; Adrian J. Reber, Centers for Disease Control and Prevention; Amrita Kumar, Centers for Disease Control and Prevention; Patricia Ramos, Centers for Disease Control and Prevention; Gabriel Sica, Emory University; Nedzad Music, Centers for Disease Control and Prevention; Zhu Guo, Centers for Disease Control and Prevention; Margarita Mishina, Centers for Disease Control and Prevention; James Stevens, Centers for Disease Control and Prevention; Ian A. York, Centers for Disease Control and Prevention; Joshy Jacob, Emory University; Suryaprakash Sambhara, Centers for Disease Control and Prevention
• Language: English
• Date: 2016-11-16
• Publisher: Nature Publishing Group
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2016.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/srep37341
• Title of Journal or Parent Work: Scientific Reports
• ISSN: 2045-2322
• Volume: 6
• Start Page: 37341
• End Page: 37341
• Grant/Funding Information: This work was supported by the Influenza Division, Centers for Disease Control and Prevention.
• Keywords: Inactivated vaccines; INCREASED RISK; A VIRUS-INFECTION; ANTIGEN PRESENTATION; DENDRITIC CELLS; RESPIRATORY-INFECTION; Science & Technology; CD8(+) T-CELLS; IN-VIVO; HETEROSUBTYPIC IMMUNITY; LETHAL INFECTION; Influenza virus; PANDEMIC H1N1 INFLUENZA; Multidisciplinary Sciences
• Research Categories: Biology, Microbiology; Health Sciences, Immunology

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.