Influenza infection is difficult to prevent, control, and treat because of rapid viral mutation, fast
disease progression, and high mortality. Vaccination is the main means by which to prevent and control
influenza, but effectiveness is limited in that poor cellular uptake and weak immunogenicity of
vaccines provides less than optimal host protection. Liposomal
influenza vaccines are a promising strategy to overcome these limitations and the use of liposomal immune modulators and
intranasal administration of liposomal
influenza vaccines may be a means by which to improve
influenza protection. The cationic
lipids, i.e.,
dimethyldioctadecylammonium (
DDA), 1,2-dioctadecanoyl-sn-glycero-3-phosphocholine (DSPC), and D-α-
tocopherol polyethylene glycol 1000 (
TPGS) can form blank
liposomes, which can incorporate
influenza antigens to produce an
influenza vaccine (
DDA-DSPC-
TPGS). Herein, this
vaccine was shown to induce dendritic cell maturation, increase host cellular uptake of the
vaccine, and enhance immune responses both in vitro and in vivo. The addition of
TPGS, as an amphiphilic immune adjuvant, significantly reduced the toxicity of the
DDA liposomal
influenza vaccine. Further, the
polyethylene glycol component and
tocopherol structure of
TPGS enhanced the cellular uptake of the
vaccine by means of stealth properties and the capacity to inhibit cellular efflux. After nasal mucosal immunization, enhanced cellular uptake rates and abundant immune cells in the nasopharyngeal-associated lymphoid tissue promoted the production of
immunoglobulin A,
immunoglobulin G1, and
interferon-γ, which in turn mediated a more robust immune response against influenza virus. In summary, the
DDA-DSPC-
TPGS influenza vaccine is a safe and effective means by which to activate the immune system. The results herein provide an effective strategy by which to overcome current difficulties associated with the prevention and treatment of
influenza.