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Journal of Virology, December 2006, p. 11756-11766, Vol. 80, No. 23
0022-538X/06/$08.00+0     doi:10.1128/JVI.01460-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Cellular Immune Responses in Children and Adults Receiving Inactivated or Live Attenuated Influenza Vaccines

Xiao-Song He,^1,2* Tyson H. Holmes,³ Caiqiu Zhang,^1,2 Kutubuddin Mahmood,⁴ George W. Kemble,⁴ David B. Lewis,⁵ Cornelia L. Dekker,⁵ Harry B. Greenberg,^1,2,6, and Ann M. Arvin^5,

Departments of Medicine,¹ Health Research and Policy (Biostatistics),³ Pediatrics,⁵ Microbiology and Immunology, Stanford University School of Medicine, Stanford, California 94305,⁶ VA Palo Alto Health Care System, Palo Alto, California 94304,² Medimmune Vaccines, Mountain View, California 94303⁴

Received 11 July 2006/ Accepted 5 September 2006

The patterns of cellular immune responses induced by live attenuated influenza vaccine (LAIV) versus those of the trivalent inactivated influenza vaccine (TIV) have not been studied extensively, especially in children. The goals of this study were to evaluate the effects of TIV and LAIV immunization on cellular immunity to live influenza A virus in children and adults and to explore factors associated with variations in responses to influenza vaccines among individuals. A gamma interferon (IFN-) flow cytometry assay was used to measure IFN--producing (IFN-⁺) NK and T cells in peripheral blood mononuclear cell cultures stimulated with a live influenza A virus strain before and after LAIV or TIV immunization of children and adults. The mean percentages of influenza A virus-specific IFN-⁺ CD4 and CD8 T cells increased significantly after LAIV, but not TIV, immunization in children aged 5 to 9 years. No increases in the mean levels of influenza A virus-reactive IFN-⁺ T cells and NK cells were observed in adults given LAIV or TIV. TIV induced a significant increase in influenza A virus-reactive T cells in 6-month- to 4-year-old children; LAIV was not evaluated in this age group. The postvaccination changes (n-fold) in the percentages of influenza A virus-reactive IFN-⁺ T and NK cells in adults were highly variable and correlated inversely with the prevaccination percentages, in particular with that of the CD56^dim NK cell subset. In conclusion, our findings identify age, type of vaccine, and prevaccination levels of immune reactivity to influenza A virus as factors significantly associated with the magnitude of cellular immune responses to influenza vaccines.

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* Corresponding author. Mailing address: VA Palo Alto Health Care System 154C, 3801 Miranda Avenue, Palo Alto, CA 94304. Phone: (650) 493-5000, ext. 66135. Fax: (650) 852-3259. E-mail: xiaosong{at}stanford.edu.

Published ahead of print on 13 September 2006.

H.B.G. and A.M.A. contributed equally to this work.

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Journal of Virology, December 2006, p. 11756-11766, Vol. 80, No. 23
0022-538X/06/$08.00+0     doi:10.1128/JVI.01460-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

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