During the A2 influenza epidemic of the winter of 1967 to 1968, commercially available inactivated influenza virus vaccine, bivalent, was administered by aerosol to 386 volunteers to test its efficacy in protecting against influenza illness. The illness rate in volunteers receiving the aerosolized vaccine was compared to that of 269 persons receiving the same vaccine subcutaneously and to that of 1,490 persons who received either sodium chloride solution or no inoculation. The group receiving aerosolized influenza vaccine had 79% fewer illnesses while subcutaneously immunized volunteers had 27% fewer illnesses, when compared to the control groups receiving no immunization. In addition to its superiority in ability to protect against naturally occurring influenza illness, the aerosolized vaccine led to a significantly lower incidence of side effects and to a significantly shorter duration of illness in those few who became ill.
Waldman RH, Mann JJ, Small PA. Immunization Against InfluenzaPrevention of Illness in Man by Aerosolized Inactivated Vaccine. JAMA. 1969;207(3):520-524. doi:10.1001/jama.1969.03150160032007