Center of Excellence for Infectious Diseases, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, 5001 El Paso Drive, El Paso, TX 79905, USA.
Vaccine. 2013 Feb 4;31(7):1009-11. doi: 10.1016/j.vaccine.2012.12.054. Epub 2013 Jan 4.
We have previously shown that an adenovirus vectored vaccine delivered intramuscularly or intranasally was effective in protection against botulism in a mouse model. The adenoviral vector encodes a human codon-optimized heavy chain C-fragment (H(C)50) of botulinum neurotoxin type C (BoNT/C). Here, we evaluate the same vaccine candidate as an oral vaccine against BoNT/C in a mouse model. To elicit protective immunity, the mice were orally vaccinated with a single dose of 1×10(4) to 1×10(7)plaque forming units (pfu) of the adenoviral vector. The immune sera, collected six weeks after oral vaccination with 2×10(7)pfu adenovirus, have shown an ability to neutralize the biological activity of BoNT/C in vitro. Additionally, animals receiving a single dose of 2×10(6)pfu adenovirus or greater were completely protected against challenge with 100×MLD(50) of BoNT/C. The data demonstrated the feasibility to develop an adenovirus-based oral vaccine against botulism.
我们之前已经证明，肌肉内或鼻内接种的腺病毒载体疫苗在小鼠模型中对肉毒中毒具有保护作用。腺病毒载体编码经人密码子优化的肉毒梭菌神经毒素 C 型（BoNT/C）重链 C 片段（H(C)50）。在这里，我们评估了同一种疫苗候选物作为口服 BoNT/C 疫苗在小鼠模型中的效果。为了引发保护性免疫，用 1×10(4)到 1×10(7)噬斑形成单位（pfu）的腺病毒载体对小鼠进行单次口服疫苗接种。在口服接种 2×10(7)pfu 腺病毒六周后收集的免疫血清，已显示出在体外中和 BoNT/C 生物学活性的能力。此外，接受 2×10(6)pfu 或更高剂量腺病毒的动物完全免受 100×MLD(50)BoNT/C 的挑战。这些数据表明，开发基于腺病毒的口服肉毒中毒疫苗是可行的。
