Aerosol immunization with NYVAC and MVA vectored vaccines is safe, simple, and immunogenic
Aerosol immunization with NYVAC and MVA vectored vaccines is safe, simple, and immunogenic
复制标题
DOI：
10.1073/pnas.0705191105
复制
发表时间：
2008-02-12
影响因子：
11.1
通讯作者：
Le Pape, Alain
中科院分区：
文献类型：
--
作者：
Corbett, Max;Bogers, Willy M.;Le Pape, Alain
每年，全世界约有500万人死于公认的疫苗可预防的粘膜传播疾病。关于大规模疫苗接种活动，应对这一艰巨挑战的一个战略是气雾剂疫苗交付，与传统的疫苗接种路线相比，它提供了潜在的安全、后勤和节省成本的优势。此外，气雾剂疫苗接种可引发关键的粘膜免疫反应，在预防性或治疗性疫苗环境中可遏制或消除粘膜传播的病原体。在目前的临床前非人类灵长类动物研究中，我们论证了重组痘病毒疫苗载体NYVAC和MVA用于气雾剂疫苗接种的可行性。用放射性标记、气雾剂注射的NYVAC-C(Clade C，HIV-1疫苗)和MVA-HPV疫苗进行的实时体内闪烁试验显示，黏膜向呼吸道输送一致。此外，疫苗的气雾剂注射是安全的，不会引起疫苗相关的病理，特别是在大脑和肺部，并且具有免疫原性。注射DNA-C/NYVAC-C Prime/Boost方案后，全身和肛门生殖器HIV特异性免疫反应在免疫后5个月仍可检测到。因此，使用NYVAC和MVA载体疫苗的气雾剂疫苗构成了大规模疫苗努力对抗粘膜传播病原体的工具。
Each year, approximately five million people die worldwide from putatively vaccine-preventable mucosally transmitted diseases. With respect to mass vaccination campaigns, one strategy to cope with this formidable challenge is aerosol vaccine delivery, which offers potential safety, logistical, and cost-saving advantages over traditional vaccination routes. Additionally, aerosol vaccination may elicit pivotal mucosal immune responses that could contain or eliminate mucosally transmitted pathogens in a preventative or therapeutic vaccine context. In this current preclinical non-human primate investigation, we demonstrate the feasibility of aerosol vaccination with the recombinant poxvirus-based vaccine vectors NYVAC and MVA. Real-time in vivo scintigraphy experiments with radiolabeled, aerosol-administered NYVAC-C (Clade C, HIV-1 vaccine) and MVA-HPV vaccines revealed consistent mucosal delivery to the respiratory tract. Furthermore, aerosol delivery of the vaccines was safe, inducing no vaccine-associated pathology, in particular in the brain and lungs, and was immunogenic. Administration of a DNA-C/NYVAC-C prime/boost regime resulted in both systemic and anal-genital HIV-specific immune responses that were still detectable 5 months after immunization. Thus, aerosol vaccination with NYVAC and MVA vectored vaccines constitutes a tool for large-scale vaccine efforts against mucosally transmitted pathogens.