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Clinical and Vaccine Immunology, August 2008, p. 1171-1175, Vol. 15, No. 8
1071-412X/08/$08.00+0     doi:10.1128/CVI.00090-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Influenza Virus Vaccination Induces Interleukin-12/23 Receptor β1 (IL-12/23Rβ1)-Independent Production of Gamma Interferon (IFN-{gamma}) and Humoral Immunity in Patients with Genetic Deficiencies in IL-12/23Rβ1 or IFN-{gamma} Receptor I{triangledown}

Tjitske de Boer,1 Jaap T. van Dissel,1 Taco W. J. Kuijpers,2 Guus F. Rimmelzwaan,3 Frank P. Kroon,1,§ and Tom H. M. Ottenhoff1,§*

Department of Infectious Diseases, LUMC, Leiden, The Netherlands,1 Emma Children's Hospital at the Academic Medical Center (AMC), Amsterdam, The Netherlands,2 Department of Virology, EUR, Rotterdam, The Netherlands3

Received 14 March 2008/ Returned for modification 14 April 2008/ Accepted 2 June 2008

To investigate whether protective immune responses can be induced in the absence of normal interleukin-12/23/gamma interferon (IL-12/23/IFN-{gamma}) axis signaling, we vaccinated with the seasonal influenza virus subunit vaccine two patients with complete IL-12/23 receptor β1 (IL-12/23Rβ1) deficiencies, two patients with partial IFN-{gamma} receptor I (pIFN-{gamma}RI) deficiencies, and five healthy controls. Blood samples were analyzed before, 7 days after, 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 virus-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 virus-specific IFN-{gamma} responses were IL-12/23 independent, in striking contrast to mycobacterium-induced IFN-{gamma} production. In conclusion, influenza virus vaccination induces IL-12/23-independent IFN-{gamma} production by T cells and can result in sufficient humoral protection in both IL-12/23Rβ1- and pIFN-{gamma}RI-deficient individuals.

* Corresponding author. Mailing address: Department of Infectious Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands. Phone: 31-71-5262620. Fax: 31-71-5266758. E-mail: t.h.m.ottenhoff{at}lumc.nl

{triangledown} Published ahead of print on 18 June 2008.

§ These authors share senior authorship.

Clinical and Vaccine Immunology, August 2008, p. 1171-1175, Vol. 15, No. 8
1071-412X/08/$08.00+0     doi:10.1128/CVI.00090-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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