Aerosol immunization with NYVAC and MVA vectored vaccines is safe, simple, and immunogenic
Published online on February 11, 2008, 10.1073/pnas.0705191105
pnas.org
Max Corbetta,b, Willy M. Bogersc, Jonathan L. Heeneyc, Stefan Gerberd, Christian Genine, Arnaud Didierlaurentf, Herman Oostermeijerc, Rob Dubbesc, Gerco Braskampc, Stéphanie Lerondelg, Carmen E. Gomezh, Mariano Estebanh, Ralf Wagneri, Ivanella Kondovac, Petra Mooijc, Sunita Balla-Jhagjhoorsinghj, Niels Beenhakkerc, Gerrit Koopmanc, Sjoerd van der Burgk, Jean-Pierre Kraehenbuhla,l,m, and Alain Le Papen
aEuroVacc Foundation, Institut Swisse de Recherche Expérimentale sur la Cancer (ISREC), CH-1066, Epalinges, Switzerland; bLaboratory of AIDS Immunopathogenesis, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland; lSwiss Institute for Experimental Cancer Research, CH-1066, Epalinges, Switzerland; cFoundation Biomedical Primate Research Center, 2280 GH, Rijswijk, The Netherlands; dDepartment of Gynecology and Obstetric, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland; eUniversity Jean Monnet (UJM) of St. Etienne, 42023 St. Etienne, France; fKennedy Institute of Rheumatology, Imperial College, London SW7 24Z, England; gTAAM, Small Animal Imaging Center, Centre National de la Recherche Scientifique, Unités Propres de Service 44, 45071 Orléans, France; hDepartment of Molecular and Cellular Biology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Cientificas, Ciudad Universitaria Cantoblanco, 28049 Madrid, Spain; jDepartment of Microbiology, Institute of Tropical Medicine, 2000 Antwerpen, Belgium; kDepartment of Clinical Oncology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands; nInstitut National de la Santé et de la Recherche Médicale U618, IFR135, Université François Rabelais, 37032 Tours, France; and iMolecular Microbiology and Gene Therapy Unit, Institute of Medical Microbiology and Hygiene, University of Regensburg, Franz-Josef-Strauss Allee 11, D-93053 Regensburg, Germany
Edited by John J. Mekalanos, Harvard Medical School, Boston, MA, and approved December 18, 2007 (received for review June 8, 2007)
Abstract
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.
MVA HPV | non-human primate | NYVAC HIV | preclinical study | aerosol vaccine assessment
Footnotes
Author contributions: M.C. and W.M.B. contributed equally to this work; M.C., W.M.B., J.L.H., S.G., C.G., A.D., G.B., S.L., M.E., R.W., G.K., J.-P.K., and A.L.P. designed research; M.C., C.G., A.D., H.O., R.D., G.B., S.L., C.E.G., R.W., I.K., P.M., S.B.-J., N.B., G.K., and A.L.P. performed research; M.C., S.G., S.L., C.E.G., M.E., R.W., S.H.v.d.B., and A.L.P. contributed new reagents/analytic tools; M.C., W.M.B., J.L.H., C.G., H.O., R.D., S.L., R.W., I.K., P.M., and A.L.P. analyzed data; and M.C., W.M.B., A.D., J.-P.K., and A.L.P. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission. |
