Please cite this paper as: Svindland et al. The mucosal and systemic immune responses elicited by a chitosanâadjuvanted intranasal influenza H5N1 vaccine. Influenza and Other Respiratory Viruses DOI:10.1111/j.1750â2659.2011.00271.x.
Backgroundâ Development of influenza vaccines that induce mucosal immunity has been highlighted by the World Health Organisation as a priority (Vaccine 2005;23:1529). Doseâsparing strategies and an efficient massâvaccination regime will be paramount to reduce the morbidity and mortality of a future H5N1 pandemic.
Objectivesâ This study has investigated the immune response and the doseâsparing potential of a chitosanâadjuvanted intranasal H5N1 (RGâ14) subunit (SU) vaccine in a mouse model.
Methodsâ Groups of mice were intranasally immunised once or twice with a chitosan (5âmg/ml)âadjuvanted SU vaccine [7·5, 15 or 30âÎŒg haemagglutinin (HA)] or with a nonâadjuvanted SU vaccine (30âÎŒg HA). For comparison, another group of mice were intranasally immunised with a whole H5N1 (RGâ14) virus (WV) vaccine (15âÎŒg HA), and the control group consisted of unimmunised mice.
Resultsâ The chitosanâadjuvanted SU vaccine induced an immune response superior to that of the nonâadjuvanted SU vaccine. Compared with the nonâadjuvanted SU group, the chitosanâadjuvanted SU vaccine elicited higher numbers of influenzaâspecific antibodyâsecreting cells (ASCs), higher concentrations of local and systemic antibodies and correspondingly an improved haemagglutination inhibition (HI) and single radial haemolysis (SRH) response against both the homologous vaccine strain and drifted H5 strains. We measured a mixed Tâhelper 1/Tâhelper 2 cytokine response in the chitosanâadjuvanted SU groups, and these groups had an increased percentage of virusâspecific CD4+ T cells producing two Thelper 1 (Th1) cytokines simultaneously compared with the nonâadjuvanted SU group. Overall, the WV vaccine induced higher antibody concentrations in sera and an HI and SRH response similar to that of the chitosanâadjuvanted SU vaccine. Furthermore, the WV vaccine formulation showed a stronger bias towards a Tâhelper 1 profile than the SU vaccine and elicited the highest frequencies of CD4+ Th1 cells simultaneously secreting three different cytokines (INFÎł+, IL2+ and INFα+). As expected, two immunisations gave a better immune response than one in all groups. The control group had very low or not detectable results in the performed immunoassays.
Conclusionâ The crossâclade serum reactivity, improved Bâ and Tâcell responses and doseâsparing potential of chitosan show that a chitosanâadjuvanted intranasal influenza vaccine is a promising candidate vaccine for further preclinical development.