Nayak Jennifer L, Richards Katherine A, Yang Hongmei, Treanor John J, Sant Andrea J
Division of Infectious Diseases, Department of Pediatrics.
David H. Smith Center for Vaccine Biology and Immunology, Department of Microbiology and Immunology.
J Infect Dis. 2015 May 1;211(9):1408-17. doi: 10.1093/infdis/jiu616. Epub 2014 Nov 6.
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.
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.
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.
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.
先前接种禽流感疫苗会使再次接种时产生更快且更强的中和抗体反应，但目前尚不清楚CD4(+) T细胞在此过程中所起的作用。
将先前参加过甲型流感（H5N1）灭活疫苗试验的人类受试者和未接触过疫苗的受试者用甲型流感/印度尼西亚/5/05（H5N1）灭活亚单位疫苗进行免疫。通过微量中和试验测量中和抗体反应，并使用干扰素γ酶联免疫斑点试验对血凝素（HA）特异性和核蛋白（NP）特异性CD4(+) T细胞反应进行定量分析。
在先前未接种过疫苗的组中，接种疫苗后诱导出的针对HA的CD4(+) T细胞反应几乎检测不到，而接种过疫苗的受试者在基线时就有易于检测到的HA特异性记忆CD4(+) T细胞，并且接种疫苗后对HA特异性表位产生了更强的反应。在检查保守的NP特异性CD4(+) T细胞反应时，两组之间没有差异。有趣的是，对H5 HA蛋白产生CD4(+) T细胞反应的个体再次接种后的中和抗体反应显著更高，而NP特异性反应未观察到这种相关性。
这些发现表明，大流行前的疫苗接种会导致HA特异性CD4(+) T细胞群体增多，当再次接触发生抗原漂移的疫苗毒株时，这些细胞会被募集，并有助于产生更强、更快的中和抗体反应。
