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J Infect Dis. 2015 May 1;211(9):1408-17. doi: 10.1093/infdis/jiu616. Epub 2014 Nov 6.

Effect of influenza A(H5N1) vaccine prepandemic priming on CD4+ T-cell responses.

Author information

1
Division of Infectious Diseases, Department of Pediatrics.
2
David H. Smith Center for Vaccine Biology and Immunology, Department of Microbiology and Immunology.
3
Department of Biostatistics and Computational Biology.
4
Division of Infectious Diseases, Department of Medicine, University of Rochester Medical Center, New York.

Abstract

INTRODUCTION:

Previous priming with avian influenza vaccines results in more rapid and more robust neutralizing antibody responses upon revaccination, but the role CD4(+) T cells play in this process is not currently known.

METHODS:

Human subjects previously enrolled in trials of inactivated influenza A(H5N1) vaccines and naive subjects were immunized with an inactivated subunit influenza A/Indonesia/5/05(H5N1) vaccine. Neutralizing antibody responses were measured by a microneutralization assay, and hemagglutinin (HA)-specific and nucleoprotein (NP)-specific CD4(+) T-cell responses were quantified using interferon γ enzyme-linked immunosorbent spot assays.

RESULTS:

While vaccination induced barely detectable CD4(+) T-cell responses specific for HA in the previously unprimed group, primed subjects had readily detectable HA-specific memory CD4(+) T cells at baseline and mounted a more robust response to HA-specific epitopes after vaccination. There were no differences between groups when conserved NP-specific CD4(+) T-cell responses were examined. Interestingly, neutralizing antibody responses following revaccination were significantly higher in individuals who mounted a CD4(+) T-cell response to the H5 HA protein, a correlation not observed for NP-specific responses.

CONCLUSIONS:

These findings suggest that prepandemic vaccination results in an enriched population of HA-specific CD4(+) T cells that are recruited on rechallenge with a drifted vaccine variant and contribute to more robust and more rapid neutralizing antibody responses.

KEYWORDS:

CD4+ T cells; H5N1; avian influenza; influenza; influenza vaccine; pandemic influenza

PMID:
25378637
PMCID:
PMC4425838
DOI:
10.1093/infdis/jiu616
[Indexed for MEDLINE]
Free PMC Article

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