Assessment of route of administration and dose escalation for an adenovirus-based influenza A Virus (H5N1) vaccine in chickens.
Assessment of route of administration and dose escalation for an adenovirus-based influenza A Virus (H5N1) vaccine in chickens.
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评估基于腺病毒的甲型流感病毒 (H5N1) 鸡疫苗的给药途径和剂量递增。
DOI：
10.1128/cvi.00180-10
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Gambotto,Andrea
中科院分区：
文献类型：
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作者：
Steitz,Julia;Wagner,RobertA;Bristol,Tyler;Gao,Wentao;Donis,RubenO;Gambotto,Andrea
高致病性禽流感（HPAI）病毒引起经济上最具破坏性的家禽疾病之一。预防商业和后院鸟类疾病的HPAI疫苗必须有效，安全和廉价。最近，我们证明了基于腺病毒的H5N1高致病性禽流感疫苗（Ad5.HA）在鸡中的有效性。为了进一步评估Ad5.HA疫苗的潜力及其成本效益，进行了确定鸡中最小有效剂量和最佳给药途径的研究。低至每只鸡107个病毒颗粒（vp）的基于腺病毒的H5N1疫苗的剂量足以产生强有力的体液免疫应答，这与先前报道的保护水平相关。评价了几种给药途径，包括阴道内、结膜、皮下和卵途径，以获得最佳疫苗给药。然而，只有皮下免疫途径诱导了令人满意的流感病毒特异性抗体水平。重要的是，这些研究确定了疫苗诱导的免疫力对来自不同进化枝的H5N1毒株具有交叉反应性，强调了交叉保护的潜力。我们的研究结果表明，Ad5.HA HPAI疫苗是安全有效的，具有交叉保护的潜力。Ad5.HA的易制造性和成本效益使其成为具有保护家禽免受HPAI病毒感染的能力的优秀禽流感候选疫苗。考虑到目前用于家禽应用的流感疫苗技术的局限性，旨在克服这些局限性的任何努力都是非常重要的。
Highly pathogenic avian influenza (HPAI) virus causes one of the most economically devastating poultry diseases. An HPAI vaccine to prevent the disease in commercial and backyard birds must be effective, safe, and inexpensive. Recently, we demonstrated the efficacy of an adenovirus-based H5N1 HPAI vaccine (Ad5.HA) in chickens. To further evaluate the potential of the Ad5.HA vaccine and its cost-effectiveness, studies to determine the minimal effective dose and optimal route of administration in chickens were performed. A dose as low as 107viral particles (vp) of adenovirus-based H5N1 vaccine per chicken was sufficient to generate a robust humoral immune response, which correlated with the previously reported level of protection. Several routes of administration, including intratracheal, conjunctival, subcutaneous, andin ovoroutes, were evaluated for optimal vaccine administration. However, only the subcutaneous route of immunization induced a satisfactory level of influenza virus-specific antibodies. Importantly, these studies established that the vaccine-induced immunity was cross-reactive against an H5N1 strain from a different clade, emphasizing the potential of cross-protection. Our results suggest that the Ad5.HA HPAI vaccine is safe and effective, with the potential of cross-clade protection. The ease of manufacturing and cost-effectiveness make Ad5.HA an excellent avian influenza vaccine candidate with the ability to protect poultry from HPAI virus infection. Considering the limitations of the influenza vaccine technology currently used for poultry applications, any effort aimed at overcoming those limitations is highly significant.