A novel intranasal flu vaccine
Annual outbreaks of influenza virus infections pose a particular health threat, especially to the elderly or patients suffering from chronic conditions. Despite general perception, vaccines are the most effective means of defense against influenza. To overcome any potential barriers that limit vaccine uptake via the intramuscular (IM) route, the EU-funded 'Nasal pandemic influenza vaccine' (NASPANVAC) project proposed to develop a prototype vaccine against the influenza strain H5N1 that could be delivered intranasally. Detailed information on the project design and specific objectives can be found on the project website . Delivery of the vaccine by the nasal route offers the advantage of targeting the mucosal site of virus entry and principal location of its replication. It is also more effective at stimulating mucosal IgA antibodies, which provide immunological memory against different strains of influenza. Immunity to influenza in humans is multifactorial, with both innate and humoral responses implicated. The aim of the NASPANVAC project was to develop a vaccine that stimulates both local and systemic immune responses. In order to address poor immunogenicity as related to the avian H5 influenza strain, scientists used an inactivated form of the surface subunit antigen of the H5N1 strain. Different formulations of the adjuvant chitosan were chosen to augment immune responses, with both liquid and powder vaccine formulations proving stable and suitable for clinical use. These formulations were initially evaluated for their ability to raise innate immune responses in vitro, following which scientists carried out in vivo immunology and efficacy studies. Serological assays on immunised mouse and ferret sera demonstrated effective serology responses. Further work in mice indicated that it is possible to enhance immune responses by including a parenteral (subcutaneous) priming step of antigen administration prior to intranasal vaccination. Proof of efficacy of candidate liquid chitosan-adjuvanted vaccines was demonstrated in a challenge study in ferrets. Importantly, nasally immunised animals were in some cases fully protected against clinical symptoms after challenge with live H5N1 virus, which proved to be lethal in unvaccinated animals and those given unadjuvanted vaccine. The studies also clearly demonstrated a dependence of severity of H5N1 disease and protective outcomes on the route of challenge. Based on the promising nonclinical data obtained, a chitosan-adjuvanted vaccine formulation has provisionally been chosen for a Phase I proof-of-principle clinical study. Given the socioeconomic impact of influenza infections and the threat of an avian influenza pandemic, the NASPANVAC intranasal vaccine offers an effective solution for mass-vaccination and for targeting the virus at the point of entry.
