State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China.
State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China.
Vaccine. 2018 Apr 12;36(16):2199-2206. doi: 10.1016/j.vaccine.2018.02.050. Epub 2018 Mar 13.
Human adenoviruses types 3 (HAdV-3), 7 (HAdV-7) and 55 (HAdV-55) are major pathogens of acute respiratory infections (ARI) in children and adults. More than one type of HAdV can infect patients simultaneously, and the infections are sometimes fatal. However, there is currently no vaccine approved for general use in children and adults. Thus, development of a multivalent HAdV vaccine to combat HAdV infection becomes imperative. In this study, we constructed a new recombinant trivalent human adenovirus vaccine (rAdMHE3-h55), which expresses the hexon protein of HAdV-55 in the E3 region of rAdMHE3, a previously prepared bivalent vaccine candidate against HAdV-3 and HAdV-7. The results of in vitro neutralization assays indicate that rAdMHE3-h55 can induce the production of neutralizing antibodies against HAdV-3, HAdV-7, and HAdV-55 in mice. Furthermore, immunization with the recombinant trivalent vaccine candidate completely protected the mice challenged with HAdV-3, HAdV-7, orHAdV-55, respectively, showing lower lung viral loads and less lung Pathological changes was compared with those in unvaccinated mice. The current findings contribute to the development of a new adenovirus vaccine candidate and also advance this construction method for the generation of recombinant adenovirus vaccines. In conclusion, our recombinant trivalent vaccine rAdMHE3-h55 can provides protection against challenge with HAdV-3, HAdV-7, or HAdV-55 in mice. Future work of optimizing this vaccine candidate may lead to a more effective way of preventing respiratory diseases caused by common human adenoviruses.
人腺病毒 3 型(HAdV-3)、7 型(HAdV-7)和 55 型(HAdV-55)是人呼吸道感染(ARI)的主要病原体。一种以上的 HAdV 可同时感染患者,感染有时是致命的。然而,目前尚无批准用于儿童和成人的通用疫苗。因此,开发一种多价 HAdV 疫苗来对抗 HAdV 感染变得势在必行。在这项研究中,我们构建了一种新的重组三价人腺病毒疫苗(rAdMHE3-h55),该疫苗在之前制备的针对 HAdV-3 和 HAdV-7 的二价疫苗候选物 rAdMHE3 的 E3 区表达 HAdV-55 的 hexon 蛋白。体外中和试验结果表明,rAdMHE3-h55 可诱导小鼠产生针对 HAdV-3、HAdV-7 和 HAdV-55 的中和抗体。此外,用重组三价疫苗候选物免疫完全保护了分别用 HAdV-3、HAdV-7 或 HAdV-55 攻击的小鼠,与未接种疫苗的小鼠相比,肺部病毒载量更低,肺部病理变化更少。目前的研究结果为开发新的腺病毒疫苗候选物做出了贡献,并推进了这种用于生成重组腺病毒疫苗的构建方法。总之,我们的重组三价疫苗 rAdMHE3-h55 可在小鼠中提供针对 HAdV-3、HAdV-7 或 HAdV-55 攻击的保护。优化这种疫苗候选物的未来工作可能会导致预防由常见人类腺病毒引起的呼吸道疾病的更有效方法。