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

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...

Full description

Saved in:
Bibliographic Details
Published inScientific reports Vol. 6; no. 1; p. 37341
Main Authors Kim, Jin Hyang, Reber, Adrian J., Kumar, Amrita, Ramos, Patricia, Sica, Gabriel, Music, Nedzad, Guo, Zhu, Mishina, Margarita, Stevens, James, York, Ian A., Jacob, Joshy, Sambhara, Suryaprakash
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 16.11.2016
Nature Publishing Group
Subjects
13/106
13/21
13/51
631/250/255/1578
631/250/590/1883
64/60
Antibodies
Antigen presentation
CD8 antigen
Cell activation
Humanities and Social Sciences
Immunization
Immunoregulation
Infections
Inflammation
Influenza
Lymphocytes T
Morbidity
multidisciplinary
Pandemics
Science
Seasons
Vaccines
Viruses
Online AccessGet full text

Cover

More Information
Summary: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.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Present address: 3805 Old Easton Road, Doylestown, PA 18902, USA.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep37341