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PMID: 18448618 Published · ppublish English Journal Article Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov't

Correlation of cellular immune responses with protection against culture-confirmed influenza virus in young children.

Clinical and vaccine immunology : CVI ·Vol. 15 ·No. 7 ·2008-07-00 ·Pages 1042-53

Forrest BD, Pride MW, Dunning AJ, Capeding MR, Chotpitayasunondh T, Tam JS, Rappaport R, Eldridge JH, Gruber WC

Abstract

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.

MeSH Terms
Administration, Intranasal Antibodies, Viral/blood,immunology Child, Preschool Double-Blind Method Hemagglutination Inhibition Tests Humans Immunity, Cellular Infant Influenza A Virus, H1N1 Subtype/immunology Influenza A Virus, H3N2 Subtype/immunology Influenza B virus/immunology Influenza Vaccines/immunology Influenza, Human/immunology,prevention & control Interferon-gamma/blood Leukocytes, Mononuclear/immunology,metabolism,virology Philippines Thailand Vaccination Vaccines, Attenuated/immunology
Chemicals
Antibodies, Viral Influenza Vaccines Vaccines, Attenuated Interferon-gamma
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Forrest Bruce D
Wyeth Vaccines Research, 401 North Middletown Road, Pearl River, NY 10965, USA. forresb@wyeth.com
Pride Michael W
Dunning Andrew J
Capeding Maria Rosario Z
Chotpitayasunondh Tawee
Tam John S
Rappaport Ruth
Eldridge John H
Gruber William C
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Article Info
Journal
Clinical and vaccine immunology : CVI
Abbr.
Clin Vaccine Immunol
ISSN
1556-679X
DOI
10.1128/CVI.00397-07
Email
forresb@wyeth.com
Published
2008-07-00
Epub
2008-00-30
Pages
1042-53
Language
English
Region
United States
NLM ID
101252125
PMCID
PMC2446637
Subset
IM
External Links
PubMed source DOI: 10.1128/CVI.00397-07 PMC Full Text
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