Human spend a lot of time indoors and indoor air quality (IAQ) has a great effect on quality of life in humans. Traditionally, bioaerosol in IAQs is focused on bacteria and fungus. Airborne viruses, particularly for the nanoparticle-type virus, on the bioaerosol particulates are associated with the quality of human health in indoor environment. We establish the human like animal model, like pig, for testing the efficacy of the nano virus like particle (VLP) vaccine for aerosol relative disease. The porcine reproductive and respiratory syndrome virus (PRRSV), which is an airborne and a droplet infection virus coated on the small size of bioaerosol, carries a major infectious disease in the pig raising industry worldwide. There are commercial vaccines including attenuated and inactivated vaccines available, but their efficacy remains to be improved. VLP represents safe and effective vaccine platforms based on nano-technology. The fusion protein of capsid protein (Cap) from the porcine circovirus 2 (PCV2) and the glycoprotein 5 (GP5) from PRRSV were expressed by E. coli system. The fusion protein self-assembled with the GP5 to become a VLP nanoparticle. For testing, BALB/c mice were immunized with 10 µg of chimeric VLP nanoparticle once, which induced neutralization by antibody responses to PRRSV. The VLP nanoparticle vaccine induced high T cell proliferation, not evident in commercial vaccines tested on mice. Our results suggest that the cheaper VLP–based nanoparticle is a possibly viable approach model for specific airborne-relative-diseases human vaccine in the future.