Park Ki Seok, Lee Jiyeung, Ahn So Shin, Byun Young-Ho, Seong Baik Lin, Baek Yun Hee, Song Min-Suk, Choi Young Ki, Na Yun Jeong, Hwang Inhwan, Sung Young Chul, Lee Chang Geun
Laboratory of Cellular Immunology, Division of Molecular and Life Sciences, POSTECH, Pohang 790-784, Republic of Korea.
Virology. 2009 Dec 20;395(2):182-9. doi: 10.1016/j.virol.2009.09.018.
Development of effective vaccines against highly pathogenic avian influenza (HPAI) H5N1 viruses is a global public health priority. Considering the difficulty in predicting HPAI H5N1 pandemic strains, one strategy used in their design includes the development of formulations with the capacity of eliciting broad cross-protective immunity against multiple viral antigens. To this end we constructed a replication-defective recombinant adenovirus-based avian influenza virus vaccine (rAdv-AI) expressing the codon-optimized M2eX-HA-hCD40L and the M1-M2 fusion genes from HPAI H5N1 human isolate. Although there were no significant differences in the systemic immune responses observed between the intramuscular prime-intramuscular boost regimen (IM/IM) and the intranasal prime-intramuscular boost regimen (IN/IM), IN/IM induced more potent CD8(+) T cell and antibody responses at mucosal sites than the IM/IM vaccination, resulting in more effective protection against lethal H5N2 avian influenza (AI) virus challenge. These findings suggest that the strategies used to induce multi-antigen-targeted mucosal immunity, such as IN/IM delivery of rAdv-AI, may be a promising approach for developing broad protective vaccines that may be more effective against the new HPAI pandemic strains.
研发针对高致病性禽流感（HPAI）H5N1病毒的有效疫苗是一项全球公共卫生重点工作。鉴于预测HPAI H5N1大流行毒株存在困难，其疫苗设计中采用的一种策略包括研发能够引发针对多种病毒抗原的广泛交叉保护性免疫的制剂。为此，我们构建了一种基于复制缺陷型重组腺病毒的禽流感病毒疫苗（rAdv-AI），该疫苗表达了来自HPAI H5N1人分离株的密码子优化的M2eX-HA-hCD40L和M1-M2融合基因。尽管在肌肉注射初免-肌肉注射加强免疫方案（IM/IM）和鼻内初免-肌肉注射加强免疫方案（IN/IM）之间观察到的全身免疫反应没有显著差异，但与IM/IM疫苗接种相比，IN/IM在黏膜部位诱导了更强的CD8(+) T细胞和抗体反应，从而对致死性H5N2禽流感（AI）病毒攻击产生了更有效的保护作用。这些发现表明，用于诱导多抗原靶向黏膜免疫的策略，如rAdv-AI的IN/IM给药，可能是开发对新的HPAI大流行毒株更有效的广泛保护性疫苗的一种有前景的方法。
