Key Laboratory of Animal Epidemiology of the Ministry of Agriculture, College of Veterinary Medicine and State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, 100094, China.
Key Laboratory of Animal Epidemiology of the Ministry of Agriculture, College of Veterinary Medicine and State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, 100094, China; Department of Research Management, Chinese Academy of Agricultural Sciences, Beijing, 100081, China.
Vet Microbiol. 2018 Jul;220:57-66. doi: 10.1016/j.vetmic.2018.05.005. Epub 2018 May 21.
The most commonly utilized inactivated influenza vaccines (IIVs) are usually deficient in cross immunity against divergent viruses. On the other hand, live attenuated influenza vaccines (LAIVs) are proved to be more effective in cross-protective immunity. We previously developed a H9N2 LAIV and verified its effective protection against a broad spectrum of H9N2 strains. In the present study, we evaluated its cross-immunity against H5N2 virus, a representative subtype of currently predominant H5 highly pathogenic avian influenza viruses. All chickens vaccinated with this LAIV survived from challenge of H5N2 virus in a lethal dose, and viral proliferation was effectively inhibited, as well as pathological lesions. Vaccination of this LAIV significantly activated H5N2-reactive CD4 and CD8 T cells in lungs. These LAIV-activated cross-reactive T cells expanded robustly following H5N2 exposure, and the increasing tendency was temporally correlated with viral clearance. Besides cellular immunity, factors of humoral immunity also play a contributing role in cross-immunity. Passively transferring H9N2 LAIV anti-serum resulted in 100% survival rate to chickens against H5N2 virus. Within components of the anti-serum, cross-binding IgGs against nucleoprotein (NP) of H5N2 virus were found of a contributing role in the cross immunity. These results indicate that this H9N2 LAIV represents a promising strategy for controlling highly pathogenic H5N2 virus in chickens. The cross immunity was partly attributed to LAIV activated H5N2-cross-reactive T cells and partly attributed to cross-binding IgGs against NP.
最常使用的灭活流感疫苗（IIV）通常对不同病毒的交叉免疫作用不足。另一方面，减毒活流感疫苗（LAIV）已被证明在交叉保护免疫方面更有效。我们之前开发了一种 H9N2 LAIV，并验证了其对广泛的 H9N2 株的有效保护作用。在本研究中，我们评估了其对 H5N2 病毒的交叉免疫力，H5N2 病毒是目前主要流行的 H5 高致病性禽流感病毒的代表性亚型。所有用这种 LAIV 接种的鸡都能从致死剂量的 H5N2 病毒攻击中存活下来，病毒增殖得到有效抑制，同时也减轻了病理损伤。该 LAIV 疫苗接种显著激活了鸡肺部的 H5N2 反应性 CD4 和 CD8 T 细胞。这些 LAIV 激活的交叉反应性 T 细胞在接触 H5N2 后迅速扩增，其增加趋势与病毒清除呈时间相关性。除了细胞免疫外，体液免疫因素也在交叉免疫中发挥作用。被动转移 H9N2 LAIV 抗血清可使鸡对 H5N2 病毒的存活率达到 100%。在抗血清的成分中，发现针对 H5N2 病毒核蛋白（NP）的交叉结合 IgG 对交叉免疫有一定作用。这些结果表明，这种 H9N2 LAIV 是控制鸡中高致病性 H5N2 病毒的一种很有前途的策略。交叉免疫力部分归因于 LAIV 激活的 H5N2 交叉反应性 T 细胞，部分归因于针对 NP 的交叉结合 IgG。
