Correlation of cellular immune responses with protection against culture-confirmed influenza virus in young children.
The highly sensitive gamma interferon (IFN-gamma) enzyme-linked immunosorbent spot (ELISPOT) assay permits the investigation of the role of cell-mediated immunity (CMI) in the protection of young children against influenza. Preliminary studies of young children confirmed that the IFN-gamma ELISPOT assay 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 of 10(7) fluorescent focus units (FFU) of a live attenuated influenza virus vaccine (CAIV-T) elicited substantial CMI responses. A commercial inactivated influenza virus vaccine elicited CMI responses only in children with some previous exposure to related influenza viruses as determined by detectable antibody levels prevaccination. 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 with 2,172 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 >or=100 spot-forming cells/10(6) peripheral blood mononuclear cells were protected against clinical influenza, establishing a possible target level of CMI for future influenza vaccine development. The ELISPOT assay for IFN-gamma is a sensitive and reproducible measure of CMI and memory immune responses and contributes to establishing requirements for the future development of vaccines against influenza, especially those used for children.
Forrest
Bruce D
BD
Wyeth Vaccines Research, 401 North Middletown Road, Pearl River, NY 10965, USA. forresb@wyeth.com
Pride
Michael W
MW
Dunning
Andrew J
AJ
Capeding
Maria Rosario Z
MR
Chotpitayasunondh
Tawee
T
Tam
John S
JS
Rappaport
Ruth
R
Eldridge
John H
JH
Gruber
William C
WC
D000281:Administration, Intranasal; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D002675:Child, Preschool; D004311:Double-Blind Method; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D007111:Immunity, Cellular; D007223:Infant; 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 / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology* / Q000517:prevention & control; D007371:Interferon-gamma / Q000097:blood*; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D010679:Philippines; D013785:Thailand; D014611:Vaccination; D014613:Vaccines, Attenuated / Q000276:immunology
D000914:Antibodies, Viral; D007252:Influenza Vaccines; D014613:Vaccines, Attenuated; D007371:Interferon-gamma