Influenza virus vaccination induces interleukin-12/23 receptor beta 1 (IL-12/23R beta 1)-independent production of gamma interferon (IFN-gamma) and humoral immunity in patients with genetic deficiencies in IL-12/23R beta 1 or IFN-gamma receptor I.
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 beta1 (IL-12/23R beta 1) 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-12/23R beta 1- and pIFN-gamma RI-deficient individuals.
de Boer
Tjitske
T
Department of Infectious Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.
van Dissel
Jaap T
JT
Kuijpers
Taco W J
TW
Rimmelzwaan
Guus F
GF
Kroon
Frank P
FP
Ottenhoff
Tom H M
TH
D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood*; D005260:Female; D006801:Humans; D016867:Immunocompromised Host; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology; D009981:Influenza B virus / Q000276:immunology; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control; D007371:Interferon-gamma / Q000096:biosynthesis*; D053711:Interleukin-12 Receptor beta 1 Subunit / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D017471:Receptors, Interferon / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D012621:Seasons; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination; D000096743:Interferon gamma Receptor
D000914:Antibodies, Viral; D007252:Influenza Vaccines; D007371:Interferon-gamma; D053711:Interleukin-12 Receptor beta 1 Subunit; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor