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The effectiveness of vaccination programs would be enhanced greatly through the availability of vaccines that can be administered simply and, preferably, painlessly without the need for timed booster injections. Tetanus is a prime example of a disease that is readily preventable by vaccination but remains a major threat to public health due to the problems associated with administration of the present vaccine. Here we show that a protective immune response against live Clostridium tetani infection in mice can be elicited by an adenovirus vector encoding the tetanus toxin C fragment when administered as a nasal or epicutaneous vaccine. The results suggest that these vaccination modalities would be effective needle-free alternatives. This is the first demonstration that absorption of a small number of vectored vaccines into the skin following topical application of a patch can provide protection against live bacteria in a disease setting.Tetanus continues to be a threat to public health with more than half a million fatalities each year being associated with infection with Clostridium tetani (23). Due to the ubiquitous distribution of the causal agent, vaccination is the most effective medical intervention for protection of the public against this deadly disease. The effectiveness of the vaccine is due, at least in part, to the fact that the sequences of the neurotoxin molecules are conserved among different strains of C. tetani, which permits elicitation of a protective immune response against all C. tetani strains through the use of a single vaccine (23). The effectiveness of the vaccine is limited, however, by the needle-based delivery method currently in use. Effective protection requires injection of three consecutive doses of the tetanus toxoid vaccine (16). Moreover, booster injections must be administered periodically during adulthood to compensate for the age-related decline in antitoxin levels (16). In developing countries, vaccine coverage against this disease is generally low due to failure to follow up as well as a lack of the trained medical personnel and facilities required for administration of the vaccine. In developed countries, although vaccine coverage in childhood is high, there is a general lack of compliance of adults with recommended schedules for booster injections (16). These factors have led to the realization that tetanus vaccination programs would be improved significantly worldwide through the development of low-cost, needle-free vaccines.Needle-free vaccination requires the development of novel vaccines that can be administered safely and effectively. Several routes of administration are being considered. Both nasal and oral immunizations have been shown to be effective in eliciting an immune response against a number of pathogens. An alternative new modality is noninvasive vaccination onto the skin (NIVS) by topical application of epicutaneous vaccines (8,10,11,17,18,22), which would offer a greater safety margin and eliminate the discomfort associated with injections. Prior to our ...

Protective immunity against avian influenza virus was elicited in chickens by single-dose in ovo vaccination with a non-replicating human adenovirus vector encoding an H5N9 avian influenza virus hemagglutinin. Vaccinated chickens were protected against both H5N1 (89% hemagglutinin homology; 68% protection) and H5N2 (94% hemagglutinin homology; 100% protection) highly pathogenic avian influenza virus challenges. Mass-administration of this bird flu vaccine can be streamlined with available robotic in ovo injectors. In addition, adenovirus-vectored vaccines can be produced rapidly and the safety margin of a non-replicating vector is superior to that of a replicating counterpart. Furthermore, this mode of vaccination is compatible with epidemiological surveys of natural avian influenza virus infections.

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