Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, Indiana, United States of America.
PLoS One. 2013 Apr 30;8(4):e62496. doi: 10.1371/journal.pone.0062496. Print 2013.
Recurrent outbreaks of H5, H7 and H9 avian influenza viruses in domestic poultry accompanied by their occasional transmission to humans have highlighted the public health threat posed by these viruses. Newer vaccine approaches for pandemic preparedness against these viruses are needed, given the limitations of vaccines currently approved for H5N1 viruses in terms of their production timelines and the ability to induce protective immune responses in the absence of adjuvants. In this study, we evaluated the feasibility of an adenovirus (AdV)-based multivalent vaccine approach for pandemic preparedness against H5, H7 and H9 avian influenza viruses in a mouse model. Replication-defective AdV vectors expressing hemagglutinin (HA) from different subtypes and nucleoprotein (NP) from one subtype induced high levels of humoral and cellular immune responses and conferred protection against virus replication following challenge with H5, H7 and H9 avian influenza virus subtypes. Inclusion of HA from the 2009 H1N1 pandemic virus in the vaccine formulation further broadened the vaccine coverage. Significantly high levels of HA stalk-specific antibodies were observed following immunization with the multivalent vaccine. Inclusion of NP into the multivalent HA vaccine formulation resulted in the induction of CD8 T cell responses. These results suggest that a multivalent vaccine strategy may provide reasonable protection in the event of a pandemic caused by H5, H7, or H9 avian influenza virus before a strain-matched vaccine can be produced.
家禽中反复出现的 H5、H7 和 H9 禽流感病毒及其偶尔向人类传播，突显了这些病毒对公共卫生构成的威胁。鉴于目前批准用于 H5N1 病毒的疫苗在生产时间和在没有佐剂的情况下诱导保护性免疫应答的能力方面存在局限性，需要针对这些病毒制定新的大流行防范疫苗方法。在这项研究中，我们评估了基于腺病毒（AdV）的多价疫苗方法在小鼠模型中针对 H5、H7 和 H9 禽流感病毒大流行防范的可行性。表达来自不同亚型的血凝素（HA）和一种亚型的核蛋白（NP）的复制缺陷型 AdV 载体诱导了高水平的体液和细胞免疫应答，并在受到 H5、H7 和 H9 禽流感病毒亚型的挑战后提供了针对病毒复制的保护。在疫苗配方中包含 2009 年 H1N1 大流行病毒的 HA 进一步扩大了疫苗的覆盖范围。在接种多价疫苗后，观察到针对 HA 茎特异性抗体的水平显著升高。在多价 HA 疫苗配方中包含 NP 导致了 CD8 T 细胞应答的诱导。这些结果表明，在生产与流行株匹配的疫苗之前，针对 H5、H7 或 H9 禽流感病毒引起的大流行，多价疫苗策略可能提供合理的保护。
