Effect of influenza A(H5N1) vaccine prepandemic priming on CD4+ T-cell responses.
BACKGROUND
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.
Division of Infectious Diseases, Department of Pediatrics.
Jennifer L
JL
Nayak
David H. Smith Center for Vaccine Biology and Immunology, Department of Microbiology and Immunology.
Katherine A
KA
Richards
Department of Biostatistics and Computational Biology.
Hongmei
H
Yang
Division of Infectious Diseases, Department of Medicine, University of Rochester Medical Center, New York.
John J
JJ
Treanor
David H. Smith Center for Vaccine Biology and Immunology, Department of Microbiology and Immunology.
Andrea J
AJ
Sant
D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D005260:Female; D006801:Humans; D007115:Immunization Schedule; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D007251:Influenza, Human / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D058873:Pandemics / Q000517:prevention & control
D007252:Influenza Vaccines
CD4+ T cells; H5N1; avian influenza; influenza; influenza vaccine; pandemic influenza