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CVI Accepts, published online ahead of print on 18 June 2008
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Clin. Vaccine Immunol. doi:10.1128/CVI.00090-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Influenza vaccination induces interleukin-12/23 receptor beta1-independent production of interferon-gamma: cellular and humoral immune response to influenza vaccine in patients with genetic deficiency in interleukin-12/23 receptor-{beta}1 or interferon-gamma receptor-1

Tjitske de Boer, Jaap T. van Dissel, Taco W. J. Kuijpers, Guus F. Rimmelzwaan, Frank P. Kroon, and Tom H.M. Ottenhoff*

Department of Infectious Diseases, LUMC, Leiden, the Netherlands; Emma Children's Hospital at the Academic Medical Center (AMC), Amsterdam, the Netherlands; Department of Virology, EUR, Rotterdam, the Netherlands

* To whom correspondence should be addressed. Email: t.h.m.ottenhoff{at}lumc.nl.


   Abstract

To investigate whether protective immune responses can be induced in the absence of normal IL-12/23/IFN-{gamma}-axis signalling, we vaccinated two patients with complete IL-12/23R{beta}1-deficiency, two patients with partial IFN-{gamma}RI deficiency, and five healthy controls with the seasonal influenza subunit vaccine. Blood samples were analysed before, and 7 and 28 days after vaccination. In most cases antibody titers reached protective levels. Moreover, although T-cell responses in patients were lower than those observed in controls, significant influenza-specific T-cell proliferation, IFN-{gamma} production, and numbers of IFN-{gamma} producing cells were found in all patients 7 days after the vaccination. Interestingly, influenza-specific IFN-{gamma} responses were IL-12/23 independent, in striking contrast to mycobacterium-induced IFN-{gamma} production. In conclusion, influenza vaccination induces IL-12/23-independent IFN-{gamma} production by T-cells, and can result in sufficient humoral protection in both IL-12/23R{beta}1- and pIFN-{gamma}RI-deficient individuals.







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