are also being developed to deliver vaccines to target sites while preventing them from degrading; current research is focused on understanding the material and physical properties of biodegradable materials to be used in nanosystems to improve vaccine efficacy. research on the movement of nasal vaccine particles is focused on developing more effective ways for these vaccines to enter the body. an animal study on mice tested how a nasal vaccine can bypass issues with entry into the nasal epithelium by taking advantage of ciliary movement. the results indicated that tubulin tyrosine ligase-like family member 1 (ttll1) knockout mice had higher levels of the vaccine antigen compared to the hetero mice. nasal spray in addition to nasal sprays, nanogels are a current area of focus for nasal vaccine research. one study created a cationic nanogel-based nasal vaccine that bound to surface proteins in the nasal cavity of mice. this binding prevented biofilm formation, which subsequently allowed for the treatment of ear infections. another recent study focused on testing a previously developed nanogel nasal vaccine to prevent pneumococcal infection in macaques. the conclusions from this study showed that macaques that received this nasal vaccine had reduced lung inflammation and bacteria in the lungs. newer research expands beyond laiv and covid-19. a single-dose nasal vaccine using live attenuated bordetella pertussis, the bacteria that causes whooping cough, was tested on young mice and compared to mice injected with an acellular vaccine. the nasal vaccine was able to prevent symptoms related to whooping cough and have effects comparable to injectable vaccines. although smallpox has been almost completely eliminated due to vaccination, there are still some cases throughout the world that warrant continuous development of smallpox vaccines. there is still research being done in the 21st century to prevent smallpox from reoccurring; a 2008 study analyzed vaccinia virus (vacv) mutants when administered intranasally to mice. the findings from this study showed that low doses of intranasal vaccinations protected the mice and therefore could be used as vectors for vaccines against smallpox and similar viruses. studies are also being conducted on humans to understand the clinical translation of nasal vaccine developments. the importance of nasal spray nozzle distance and particle distribution characteristics has been shown in a 2023 study on infants. the results indicated that the minimum efficiency of the four sprays tested in vitro was 80% and the spray droplet size distribution and distance between the spray nozzle and nose can affect the vaccine’s delivery. another important characteristic of the nasal spray nozzle is the spray cone angle. a study on a 6-year-old patient to prevent covid-19 through nasal vaccination showed that the spray cone angle can affect vaccine delivery efficiency while droplet initial velocity and composition do not have as much of an impact.