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Clin. Vaccine Immunol. doi:10.1128/CVI.00397-07
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Correlation of Cellular Immune Responses with Protection Against Culture-Confirmed Influenza in Young Children

Wyeth Vaccines Research, 401 N. Middletown Road, Pearl River, NY 10960, USA; Research Institute for Tropical Medicine, Muntinlupa City, The Philippines; Queen Sikirit National Institute of Child Health, Bangkok, 10400, Thailand; Chinese University of Hong Kong, Hong Kong SAR, China

^* To whom correspondence should be addressed. Email: forresb{at}wyeth.com.

	Abstract

The highly sensitive IFN- enzyme-linked immunosorbent spot (ELISPOT) assay permits the investigation of the role of cell mediated immunity (CMI) in protection of young children against influenza. Preliminary studies in young children confirmed that the IFN- ELISPOT was a more sensitive measure of influenza memory immune responses than serum antibody and that among seronegative children aged 6 to <36 months an intranasal dose 10⁷ fluorescent focus units (FFU) of a live, attenuated influenza vaccine (CAIV-T) elicited substantial CMI responses. A commercial inactivated influenza vaccine only elicited CMI responses in children with some previous exposure to related influenza viruses as determined by prevaccination detectable antibody. The role of CMI in actual protection against community-acquired culture-confirmed clinical influenza by CAIV-T was investigated in a large randomized, double-blind, placebo-controlled dose-ranging efficacy trial in 2172 children aged 6 to <36 months in the Philippines and Thailand. The estimated protection curve indicated that the majority of infants and young children with 100 SFC/10⁶ PBMC were protected against clinical influenza establishing a possible target level of CMI for future influenza vaccine development. The ELISPOT assay for IFN- is a sensitive and reproducible measure of CMI and memory immune responses in all age groups, and contributes to establishing requirements for future development of vaccines against influenza, especially those for use in children.