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Intranasal Administration of Influenza Vaccines

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Abstract

This review article focuses on intranasal immunisation against influenza, although it also encompasses antigen uptake and processing in the nasopharyngeal passages, host defence from influenza and current influenza vaccination practices. Improvement of current vaccination strategies is clearly required; current procedures involve repeated annual injections that sometimes fail to protect the recipient. It is envisaged that nonpercutaneous immunisation would be more attractive to potential vaccinees, thus improving uptake and coverage. As well as satisfying noninvasive criteria, intranasal influenza immunisation has a number of perceived immunological advantages over current procedures. Perhaps one of the greatest attributes of this approach is its potential to evoke the secretion of haemagglutinin-specific IgA antibodies in the upper respiratory tract, the main site of viral infection.

Inactivated influenza vaccines have the advantage that they have a long history of good tolerability as injected immunogens, and in this respect are possibly more likely to be licensed than attenuated viruses. Inert influenza vaccines are poor mucosal immunogens, requiring several administrations, or prior immunological priming, in order to engender significant antibody responses. The use of vaccine delivery systems or mucosal adjuvants serves to appreciably improve the immunogenicity of mucosally applied inactivated influenza vaccines. As is the case when they are introduced parenterally, inactivated influenza vaccines are relatively poor stimulators of virus-specific cytotoxic T lymphocyte activity following nasal inoculation. Live attenuated intranasal influenza vaccines are at a far more advanced stage of clinical readiness (phase III versus phase I). With the use of live attenuated vaccines, it is possible to stimulate mucosal and cell-mediated immunological responses of a similar kind to those elicited by natural influenza infection. In children, recombinant live attenuated cold-adapted influenza viruses are well tolerated. Moreover, cold-adapted influenza viruses usually stimulate protective immunity following only a single nasal inoculation. Safety of recombinant live attenuated cold-adapted influenza viruses has also been demonstrated in high risk individuals with cystic fibrosis, asthma, cardiovascular disease and diabetes mellitus. They are not suitable for immunising immunocompromised patients, however, and are poorly efficacious in individuals with pre-existing immunity to strains closely antigenically matched with the recombinant virus. According to the reviewed literature, it is apparent that intranasal administration of vaccine as an aerosol is superior to administration as nose drops. The information reviewed in this paper suggests that nasally administered influenza vaccines could make a substantial impact on the human and economic cost of influenza.

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Authors and Affiliations

  1. Aston University, School of Pharmacy, Birmingham, B4 7ET, England

    Jim E. Eyles &  H. Oya Alpar

  2. DERA (Chemical and Biological Defence Sector), Porton Down, Salisbury, Wiltshire, England

    E. Diane Williamson

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  1. Jim E. Eyles
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  2. E. Diane Williamson
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Eyles, J.E., Williamson, E.D. & Alpar, H.O. Intranasal Administration of Influenza Vaccines. BioDrugs 13, 35–59 (2000). https://doi.org/10.2165/00063030-200013010-00005

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