Mucosal vaccination, which secretion of
immunoglobulin A (
IgA) on the mucosa is accompanied by induction of
immunoglobulin G (
IgG) in the blood, is one of the most effective ways to circumvent
influenza epidemics caused by incorrect prediction of epidemic viral strains or viral mutation. Secreted
IgA is expected to prevent hosts from being infected with heterologous viruses because this antibody cross-reacts to strains other than those used for immunization. Our previous mouse experiments revealed that intranasal
IgA with cross-reactivity was induced through nasal inoculation with inactivated whole viral particles of the H1N1 A/New Caledonia/20/99 IVR116 (NCL) strain in the presence of
hyaluronic acid modified with
tetraglycine-l-
octaarginine. In the present study, heterologous influenza virus challenge was performed to validate a potential of the
hyaluronic acid derivative as a mucosal adjuvant with cross-protective abilities. Serious
weight loss was observed when mice were nasally inoculated with inactivated NCL viruses alone and subsequently exposed to mouse-adapted infectious viruses of the H1N1 A/Puerto Rico/8/34 (PR8) strain. The symptom associated with
virus infection was hardly ever observed for mice inoculated with a mixture of the
viral antigens and
tetraglycine-l-
octaarginine-linked
hyaluronic acid, presumably due to high induction of
IgG and
IgA capable of cross-reacting to PR8 viruses. Less proliferation of PR8 viruses in those mice was also supported by an insignificant elevation of antibody levels through virus exposure. Our
polysaccharide derivative enabled hosts to acquire adaptive immunity with cross-protective abilities against heterologous
virus infection.