Corbett Max, Bogers Willy M, Heeney Jonathan L, Gerber Stefan, Genin Christian, Didierlaurent Arnaud, Oostermeijer Herman, Dubbes Rob, Braskamp Gerco, Lerondel Stéphanie, Gomez Carmen E, Esteban Mariano, Wagner Ralf, Kondova Ivanella, Mooij Petra, Balla-Jhagjhoorsingh Sunita, Beenhakker Niels, Koopman Gerrit, van der Burg Sjoerd, Kraehenbuhl Jean-Pierre, Le Pape Alain
EuroVacc Foundation, Institut Swisse de Recherche Expérimentale sur la Cancer, CH-1066, Epalinges, Switzerland.
Proc Natl Acad Sci U S A. 2008 Feb 12;105(6):2046-51. doi: 10.1073/pnas.0705191105. Epub 2008 Feb 11.
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.
全球每年约有500万人死于据信可通过疫苗预防的经黏膜传播的疾病。对于大规模疫苗接种运动而言，应对这一严峻挑战的一种策略是气溶胶疫苗递送，与传统的疫苗接种途径相比，它具有潜在的安全性、后勤便利性和成本节约优势。此外，气溶胶疫苗接种可能引发关键的黏膜免疫反应，在预防性或治疗性疫苗的背景下，这种反应可以控制或消除经黏膜传播的病原体。在当前这项临床前非人灵长类动物研究中，我们证明了使用基于重组痘病毒的疫苗载体NYVAC和MVA进行气溶胶疫苗接种的可行性。用放射性标记的、经气溶胶给药的NYVAC-C（C亚型，HIV-1疫苗）和MVA-HPV疫苗进行的实时体内闪烁扫描实验显示，疫苗能持续递送至呼吸道黏膜。此外，气溶胶递送疫苗是安全的，不会引发与疫苗相关的病理变化，尤其是在大脑和肺部，并且具有免疫原性。采用DNA-C/NYVAC-C初免/加强免疫方案可引发全身和肛门生殖器部位的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载体疫苗进行气溶胶疫苗接种是大规模疫苗研发中对抗经黏膜传播病原体的一种手段。
