Intranasal administration of influenza vaccines - Current status

This review article focuses on intranasal immunisation against influenza, a lthough it also encompasses antigen uptake and processing in the nasopharyn geal passages, host defence from influenza and current influenza vaccinatio n practices. Improvement of current vaccination strategies is clearly requi red; current procedures involve repeated annual injections that sometimes f ail to protect the recipient. It is envisaged that nonpercutaneous immunisa tion would be more attractive to potential vaccines, thus improving uptake and coverage. As well as satisfying noninvasive criteria, intranasal influe nza immunisation has a number of perceived immunological advantages over cu rrent procedures. Perhaps one of the greatest attributes of this approach i s its potential to evoke the secretion of haemagglutinin-specific IgA antib odies in the upper respiratory tract, the main site of viral infection. Inactivated influenza vaccines have the advantage that they have a long his tory of good tolerability as injected immunogens, and in this respect are p ossibly more likely to be licensed than attenuated viruses. Inert influenza vaccines are poor mucosal immunogens, requiring several administrations, o r prior immunological priming. in order to engender significant antibody re sponses. The use of vaccine delivery systems or mucosal adjuvants serves to appreciably improve the immunogenicity of mucosally applied inactivated in fluenza vaccines. As is the case when they an introduced parenterally, inac tivated influenza vaccines are relatively poor stimulators of virus-specifi c cytotoxic T lymphocyte activity following nasal inoculation. Live attenua ted intranasal influenza, vaccines are at a far I more advanced stage of cl inical readiness (phase III versus phase I). With the use of live attenuate d vaccines, it is possible to stimulate mucosal and cell-mediated immunolog ical responses of a similar kind to those elicited by natural influenza inf ection. In children, recombinant live attenuated cold-adapted influenza. vi ruses are well tolerated. Moreover, cold-adapted influenza viruses usually stimulate protective immunity following only a single nasal inoculation. Sa fety of recombinant live attenuated cold-adapted influenza viruses has also been demonstrated in high risk individuals with cystic fibrosis, asthma, c ardiovascular disease and diabetes mellitus. They are not suitable fur immu nising immunocompromised patients, however, and are poorly efficacious in i ndividuals with pre-existing immunity to strains closely antigenically matc hed with the recombinant virus. According to the reviewed literature, it is apparent that intranasal administration of vaccine as an aerosol is superi or to administration as nose drops. The information reviewed in this paper suggests that nasally administered influenza vaccines could make a substant ial impact on the human and economic cost of influenza.