Inhaled Vaccines

Inhaled vaccines, particularly measles vaccines, have received considerable attention. There has been the thought that delivery of the vaccine to the respiratory tract, the natural entry route for the pathogen, might provide an attractive therapy by engaging mucosal immunological mechanisms. Inhaled delivery is attractive for use in developing countries because of lack of suitably trained staff to administer injections and problems in disposal of used needles and syringes. Early work by Albert Sabin [29] demonstrated the feasibility followed by a mass vaccination campaign in 4 million children between 1988 and 1990 [30].

In 2002 the Measles Aerosol Vaccine Project was initiated by the WHO, CDC, and American Red Cross in order to develop a practical inhaled measles vaccine using liquid aerosol delivery [31]. Phase 1 studies showed that the aerosolized vaccine was safe and well tolerated and produced an appropriate immune response. Phase 2/3 studies were completed and showed results equivalent to sc delivery for children ages 10-35 months, but for ages 9-10 months, immune response was not as good as for sc delivery [32]. Challenges with getting good lung deposition in nose-breathing infants likely contributed to these findings. The conclusion by WHO was that for children greater than 10 months aerosol delivery should be effective. In addition, there have been efforts to develop a dry powder aerosolized vaccine using carbon dioxide-assisted bubble drying [33]. This effort was spearheaded by Aktiv-Dry with key support from a Grand Challenges grant from the Gates foundation. Preclinical studies in monkeys with the dry powder vaccine showed no adverse effects and the production of an immune response was similar to that from sc delivery [34]. Phase 1 clinical trials have been completed in healthy men with preexisting immunity to measles [35]. No adverse events were reported and the inhaled dry powder vaccine produced serologic responses generally similar to subcutaneous vaccination; however, these results are difficult to interpret because of the high baseline antibody levels.

One of the key hopes of the inhaled measles vaccines efforts is to provide access to therapies in developing countries where infrastructure for needle injection delivery systems is problematical. Another key hope is that ultimately more cost-effective therapies might also be possible [36]. This may be challenging, but with continued technological innovation, it appears to be feasible.

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