Intranasal vaccine: Factors to consider in research and development.

Most existing vaccines for human use are administered by needle-based injection. Administering vaccines needle-free intranasally has numerous advantages over by needle-based injection, but there are only a few intranasal vaccines that are currently approved for human use, and all of them are live attenuated influenza virus vaccines. Clearly, there are immunological as well as non-immunological challenges that prevent vaccine developers from choosing the intranasal route of administration. We reviewed current approved intranasal vaccines and pipelines and described the target of intranasal vaccines, i.e. nose and lymphoid tissues in the nasal cavity. We then analyzed factors unique to intranasal vaccines that need to be considered when researching and developing new intranasal vaccines. We concluded that while the choice of vaccine formulations, mucoadhesives, mucosal and epithelial permeation enhancers, and ligands that target M-cells are important, safe and effective intranasal mucosal vaccine adjuvants are needed to successfully develop an intranasal vaccine that is not based on live-attenuated viruses or bacteria. Moreover, more effective intranasal vaccine application devices that can efficiently target a vaccine to lymphoid tissues in the nasal cavity as well as preclinical animal models that can better predict intranasal vaccine performance in clinical trials are needed to increase the success rate of intranasal vaccines in clinical trials.