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Cutting Edge: Mucosal Application of a Lyophilized Viral Vector Vaccine Confers Systemic and Protective Immunity toward Intracellular Pathogens

Wolfgang Kastenmuller^1,2,,, Georg Gasteiger^1,,, Leon Stross^*,, Dirk H. Busch^, and Ingo Drexler^2,*,,

^* Institute of Virology, Helmholtz Center Munich, Munich, Germany; Institute of Virology and Institute for Medical Microbiology, Immunology, and Hygiene, Technical University Munich, Munich, Germany; and Antigen-Specific Immunotherapy and Immune-Monitoring Clinical Cooperation Groups, Helmholtz Center Munich and German Research Center for Environmental Health, Munich, Germany

A major problem of current vaccines is storage stability, often requiring strict maintenance of cold chains. In the course of the eradication of smallpox, a freeze-dried vaccinia virus (Dryvax), which proved to be very stable, was used to overcome this limitation. However, Dryvax needs to be reconstituted before usage and is administered using a bifurcated needle, procedures that pose a number of additional health risks. We report in this study that a stable, lyophilized, modified vaccinia virus Ankara (MVA) vaccine can be directly applied to the nostrils of mice without previous reconstitution. This direct mucosal application induced systemic Ab and T cell responses comparable to those achieved by i.m. administration. Importantly, mucosal application of lyophilized MVA induced long-lasting protective immunity against lethal bacterial and viral challenges. These data clearly demonstrate the potency of a simple needle-free vaccination, combining the advantages of mucosal application with the stability and efficiency of lyophilized MVA.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ W.K. and G.G. contributed equally to this work.

² Address correspondence and reprint requests to Dr. Wolfgang Kastenmuller at the current address: Lymphocyte Biology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20982. E-mail address: kastenmullerw{at}niaid.nih.gov or Dr. Ingo Drexler, Institute of Virology, Helmholtz Center Munich, 81675 Munich, Germany. E-mail address: drexler{at}helmholtz-muenchen.de

³ Abbreviations used in this paper: VACV, vaccinia virus; i.n., intranasal(ly); L.m., Listeria monocytogenes; MVA, modified VACV Ankara; WR, Western Reserve.

⁴ The online version of this article contains supplemental material.